Research Core Facilities Analysis and Activities Reports...institutional core facilities. The...

Institutional Research Core

Facilities Analysis and

Activities Reports

(July 2017-June 2018)

The University of Tennessee Health Science Center Institutional Research Core Facilities Activities and Analysis Reports

Introduction

Third Analysis, FY18 (July 2017-June 2018)

Published February 2019

Prepared by:

Dr. Tiffany N. Seagroves Associate VC for Research—Core Labs

Jane Poulos Director of Finance and Administration, Office of Research

Natalie Smith Business Manager, FCCS, RHC, mBIO, MedChem, MRC, and RHC cores

Jacqueline Toney Assistant Director (Business), LACU and RBL cores

Sarah Bloch Director of Communications & Marketing, Office of Research

Table of Contents Introduction 2

Core-Specific Evaluations

Lab Animal Care Unit (LACU) 7

Regional Biocontainment Lab (RBL) 41

Molecular Resource Center (MRC) 65

Molecular Bioinformatics (mBIO) 110

Proteomics and Metabolomics Core (PMC) 121

Flow Cytometry and Flow Sorting Core (FCCS) 138

Research Histology Core (RHC) 149

Conclusions and Global Recommendations Impacting All Cores 167

Introduction

The purpose of the annual Institutional Core Facilities core activities and core analysis reports is to cultivate the research enterprise at The University of Tennessee Health Science Center by reporting on core financial stability, key core accomplishments and the tangible and intangible return on investment in institutional core facilities by the State of Tennessee and the Institution. The ultimate goal of reporting core activities and summarizing the financial overview of each core is to optimize operations of the institutional core facilities.

The procedure for performing this analysis for Fiscal Year FY18 (July 2017-June 2018) was as follows:

• The core directors and business managers submitted initial drafts of the annualcore activity and core analysis reports between mid-October (after closeout ofFY17 ledgers) and December 2018.

• During November and December, the Associate VC for Research—Core Labsreviewed the reports with core directors and requested updates or corrections.

• Between December 2018 and January 2019, Dr. Seagroves created the finalversions of the reports, which were reviewed by the core business managers andthe Director of the Office of Research.

• The final drafts were presented to the Senior Associate VC for Research (StevenYoungentob, PhD) and to the VC for Research (Steve Goodman, PhD) on January4, 2019. The financial tables were approved by Director of Office of Research(Jane Poulos) on January 15, 2019.

• After revisions based on comments received, the Director of Communications forthe Office of Research (Sarah Bloch) prepared the final copes of the reports.

As noted in the body of the reports, there were several operational and financial achievements accomplished in FY18; Highlights are as follows:

• All cores were recommended to continue as Institutional Cores.• One Institutional Core, the Molecular Resource Center, ended FY18 with a net

income of $31,338 after accounting for the State subsidy from the TennesseeHigher Education Commission (THEC).

• There was significant investment in the Lab Animal Care Unit (LACU) to supporttwo new full-time positions (Director of Operations and Assistant Director ofOperations/QA Manager), to purchase/replace caging and to improveinfrastructure in advance of the site visit for AAALAC accreditation; the site visitteam did not identify any major deficiencies.

• As a result of revising LACU vivarium staff position description requirements andthe enhanced focus on LACU core staff training and professional development,over 94% of LACU staff became AALAS-certified.

• There was significant investment in the Regional Biocontainment Lab (RBL) tosupport the new Director hired in FY17, Dr. Colleen Jonsson, including therecruitment of a full-time RBL Services Program Manager (currently filled by Dr.

2

Dong Yang), and the purchase of several large pieces of equipment to provide expanded core services consistent with the vision of the incoming Director. New equipment included a blood analyzer to support clinical chemistry and hematology, new biosafety cabinets and several upright freezers for specimen storage.

• The RBL significantly revised its core service fee structure, adding several new service lines to the core, including the Small Animal Model-Pathology Evaluation Unit and the Pathogen Molecular Discovery Unit. New marketing materials were created to expand the RBL customer base, locally and regionally, as well as to recruit government customers and commercial entities.

• In its first year of operation (FY18), the RHC served 36 investigators across 3 Colleges, an impressive start for a new core facility.

• A partnership agreement between the Office of Research and the Department of Pediatrics was established to add the Mouse Phenotyping Mass Spectrometry (MPMS) unit to the Proteomics and Metabolomics Core (PMC). The MPMS unit offers targeted metabolomics services.

• All core facilities deployed the Agilent iLab Solutions core lab management software by the close of FY18, which has streamlined invoicing for services and the review of core financial data. Financial integration with the IRIS (UT system) will be complete by FY19.

3

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4

APPENDIX A APPENDIX B

FINAL FY18FY17FY16 Institutional Cores Overview Comparison JP Jan 21 2019.xlsxFY2018-APPENDIX C

INSTITUTIONAL CORE LAB BUDGET BALANCES

VICE CHANCELLOR FOR RESEARCH

FISCAL YEAR END 2018 `

Unrestricted

ACCT NO. ACCOUNT NAMEFY18 EXPENSE

BUDGETFY18 EXTERNAL INCOME BUDGET

FY18 NET STATE FUNDED BUDGET

Cumulative Actual Expenses

Cumulative Internal Recovery & External

IncomeBUDGET BALANCE income / (subsidy)

EXPENDITURES FUNDED BY OTHER SOURCES (a)

TOTAL income/(subsidy)

E070160 LABORATORY ANIMAL CARE (LACU) 865,209 (150,000) 715,209 3,946,369 (2,351,047) (880,113) 550,952 * (1,431,065)

E070161 FLOW CYTOMETRY (FCCS)-VC RESEARCH 16,890 (16,890) 0 166,094 (28,892) (137,202) 0 (137,202)

E070165 REGIONAL BIOCONTAINMENT LAB (RBL) 807,969 (70,000) 737,969 1,170,295 (130,680) (301,646) 0 (301,646)

E070170PROTEOMICS AND METABOLOMICS CORE (PMC) 93,360 0 93,360 163,712 (37,827) (32,525) 0 (32,525)

E070174 MOLECULAR BIOINFORMATICS (mBIO) 67,302 (5,000) 62,302 132,520 (30,046) (40,172) 0 (40,172)

E070175 RESEARCH HISTOLOGY CORE (RHC) 77,937 (59,503) 18,434 94,718 (19,663) (56,621) 0 (56,621)

E070176 MEDICINAL CHEMISTRY CORE (MedChem) 5,000 (5,000) 0 12,725 (13,833) 1,108 164,751 * (163,643)

SUBTOTAL UNRESTRICTED ACCOUNTS 1,933,667 (306,393) 1,627,274 5,686,433 (2,611,988) (1,447,171) 715,703 (2,162,874)

Restricted


BUDGET FY17 PO carryoverFY18 THEC

FUNDED BUDGETCumulative Actual

Expenses





R079700143MOLECULAR RESOURCE CENTER (MRC) of Excellence, FY18 620,121 - 620,121 853,184 (264,401) 31,338 31,338

SUBTOTAL RESTRICTED ACCOUNT 620,121 - 620,121 853,184 (264,401) 31,338 - 31,338

TOTAL ALL ACCOUNTS: 2,553,788$ (306,393)$ 2,247,395$ 6,539,617$ (2,876,389)$ (1,415,833)$ 715,703$ * (2,131,536)$

* Additional Institutional Support

Funded by VC Research and UTHSCNew and replacement Animal Caging 550,952Total LACU: $550,952

Funded by VC ResearchSalary - Jiawang Liu 80,000Dell Desktop and Laptop 3,808 Discover SP Microwave System 19,967 Reveleris Prep System 53,123 Digital Melting Pot, Thermosci, Stirrer Mantle 7,854 Total MedChem: 164,751

TOTAL: 715,703

FINAL FY18FY17FY16 Institutional Cores Overview Comparison JP Jan 21 2019.xlsxFY2016-APPENDIX A


VICE CHANCELLOR FOR RESEARCHFISCAL YEAR END 2016 `

Unrestricted

ACCT NO. ACCOUNT NAME

FY16 EXPENSE BUDGET (includes

PO carryover)FY16 EXTERNAL INCOME BUDGET







E070160LABORATORY ANIMAL CARE UNIT (LACU) 791,397 (150,000) 641,397 3,442,706 (2,795,576) (5,733) (5,733)

E070161FLOW CYTOMETRY (FCCS)-VC RESEARCH 5,000 (5,000) 0 4,714 (12,832) 8,118 8,118

E070165REGIONAL BIOCONTAINMENT LAB (RBL) 738,532 (120,000) 618,532 779,033 (195,120) 34,619 34,619

PROTEOMICS AND METABOLOMICS CORE (PMC) 0 0 0 0 0 0 1,074,817 (1,074,817)

E070167001 MOLECULAR BIOINFORMATICS 71,531 0 71,531 101,967 (39,478) 9,042 9,042

SUBTOTAL UNRESTRICTED

ACCOUNTS 1,606,460 (275,000) 1,331,460 4,328,420 (3,043,006) 46,046 1,074,817 (1,028,771)

Restricted


BUDGET

FY16 THEC FUNDED & ADJUSTED

BUDGETCumulative

Actual Expenses


Income

BUDGET BALANCE income / (subsidy-Cost

Share)



R070167013MOLECULR RESOURCE CENTER (MRC) of Excellence FY16 649,115 649,115 1,170,087 (401,738) (119,234) 202,000 (321,234)

SUBTOTAL RESTRICTED ACCOUNT 649,115 - 649,115 1,170,087 (401,738) (119,234) 202,000 (321,234)

TOTAL ALL ACCOUNTS: 2,255,575$ (275,000)$ 1,980,575$ 5,498,507$ (3,444,744)$ (73,188)$ 1,276,817$ (1,350,005)$

(a) Funded by VC Research start-up

Orbitrap Lumos Mass Spectrometer for PMC 1,027,150D. Kakhniashvili, PMC Director, salary 12/15/15 - 6/30/16 47,667Total PMC: $1,074,817

NexGen500 Sequencing System/Illumina, for MRC 202,000 Total MRC: $202,000

FINAL FY18FY17FY16 Institutional Cores Overview Comparison JP Jan 21 2019.xlsxFY2017-APPENDIX B




Unrestricted









E070160 LABORATORY ANIMAL CARE (LACU) 610,729 (20,300) 590,429 3,401,781 (2,805,431) (5,921) 0 (5,921)

E070161FLOW CYTOMETRY (FCCS)-VC RESEARCH 15,000 (15,000) 0 75,998 (24,320) (51,678) 286,592 (338,270)

E070165 REGIONAL BIOCONTAINMENT LAB (RBL) 697,204 (70,000) 627,204 784,798 (221,535) 63,941 0 63,941



E070175 RESEARCH HISTOLOGY CORE (RHC) 5,000 (5,000) 0 35,290 0 (35,290) 0 (35,290)

SUBTOTAL UNRESTRICTED ACCOUNTS 1,492,068 (115,300) 1,376,768 4,582,046 (3,107,762) (97,516) 286,592 (384,108)

Restricted

ACCT NO. ACCOUNT NAME

FY17 EXPENSE BUDGET (includes FY16 PO carryover) FY16 PO carryover

FY17 THEC FUNDED BUDGET






R070167014MOLECULAR RESOURCE CENTER (MRC) of Excellence, FY17 649,115 (46,228) 602,887 1,033,779 (408,427) (22,465) 100,651 (123,116)

SUBTOTAL RESTRICTED ACCOUNT 649,115 (46,228) 602,887 1,033,779 (408,427) (22,465) 100,651 (123,116)

TOTAL ALL ACCOUNTS: 2,141,183$ (161,528)$ 1,979,655$ 5,615,825$ (3,516,189)$ (119,981)$ 387,243$ (507,224)$

(a) Funded by VC Research start-up

YETI Flow Cytometry Analyzer 286,592Total FCCS: $286,592

STARlet NexGen Sequencing System/Hamilton 100,651 Total MRC: $100,651

5

APPENDIX C

FINAL FY18FY17FY16 Institutional Cores Overview Comparison JP Jan 21 2019.xlsxFY2018-APPENDIX C




Unrestricted









E070160 LABORATORY ANIMAL CARE (LACU) 865,209 (150,000) 715,209 3,946,369 (2,351,047) (880,113) 550,952 * (1,431,065)

E070161 FLOW CYTOMETRY (FCCS)-VC RESEARCH 16,890 (16,890) 0 166,094 (28,892) (137,202) 0 (137,202)

E070165 REGIONAL BIOCONTAINMENT LAB (RBL) 807,969 (70,000) 737,969 1,170,295 (130,680) (301,646) 0 (301,646)



E070175 RESEARCH HISTOLOGY CORE (RHC) 77,937 (59,503) 18,434 94,718 (19,663) (56,621) 0 (56,621)

E070176 MEDICINAL CHEMISTRY CORE (MedChem) 5,000 (5,000) 0 12,725 (13,833) 1,108 164,751 * (163,643)

SUBTOTAL UNRESTRICTED ACCOUNTS 1,933,667 (306,393) 1,627,274 5,686,433 (2,611,988) (1,447,171) 715,703 (2,162,874)

Restricted


BUDGET FY17 PO carryoverFY18 THEC

FUNDED BUDGETCumulative Actual

Expenses





R079700143MOLECULAR RESOURCE CENTER (MRC) of Excellence, FY18 620,121 - 620,121 853,184 (264,401) 31,338 31,338

SUBTOTAL RESTRICTED ACCOUNT 620,121 - 620,121 853,184 (264,401) 31,338 - 31,338

TOTAL ALL ACCOUNTS: 2,553,788$ (306,393)$ 2,247,395$ 6,539,617$ (2,876,389)$ (1,415,833)$ 715,703$ * (2,131,536)$

* Additional Institutional Support

Funded by VC Research and UTHSCNew and replacement Animal Caging 550,952Total LACU: $550,952

Funded by VC ResearchSalary - Jiawang Liu 80,000Dell Desktop and Laptop 3,808 Discover SP Microwave System 19,967 Reveleris Prep System 53,123 Digital Melting Pot, Thermosci, Stirrer Mantle 7,854 Total MedChem: 164,751

TOTAL: 715,703

6

Lab Animal Care Unit (LACU)

Lab Animal Care Unit (LACU) Institutional Research Core Facility Analysis Report- FY18 Written by David Hamilton, DVM; Jacqueline E. Toney; and Tiffany N. Seagroves, PhD 1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The LACU core designation as an institutional core is appropriate since it served 133 total users across 28 departments within 4 Colleges and 6 external institutions. 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. Service was provided to 121 unique internal users across 28 departments within 4 Colleges (COM, COP, CON and COD). The LACU also served 12 total external users from two academic centers (University of Memphis and LeBonheur) and 4 commercial entities (TriMetis, RxBio, Oxford Immunotech, and the VA). The top four Departments by core revenues were, in order, the Department of Anatomy & Neurobiology (COM), Department of Pediatrics (COM), Department of Physiology (COM) and Department of Pharmacology (COM). The top five users, based on the percentage of core revenues per PI versus total core revenues ($2,351,047), accounted for 25% of total revenues. These investigators were: 1) Robert Williams (Genetics, Genomics and Informatics, COM, 9.69%), 2) Jeffrey Towbin (Pediatrics, COM, 4.41%), 3) Leigh Quarles (Nephrology, COM, 4.26%), 4) Mark LeDoux (Neurology, COM, 3.39%, and 5) Jonathan Jaggar (Physiology, COM, 3.39%). The remaining internal core users accounted for the other 74.86% of revenues. 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. There were 121 unique internal users who were served across 28 departments within 4 Colleges at UTHSC and 6 unique external users. 4. Can the services for the core be outsourced more economically? No. There is no competition for this institutional core facility since it is the only accredited unit that can provide services for animal care and welfare on the UTHSC campus. There are two other institutions in Memphis that support research using laboratory animals, but the majority of UTHSC investigators do not have faculty appointments at either of these institutions. 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led to >132 PubMed-indexed publications and supported >115 extramural grants and contracts. The LACU also provided training and orientation to animal use in research to 89 investigators and research staff in FY18. 6. Is the core currently self-sufficient, or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution. After accounting for the net State appropriation ($715,209), the net subsidy was $1,431,065 (31.8%).

7


Accomplishments this past year: • A new post-doctoral fellow, Dr. Cameron Fili, started on July 3, 2017. Cameron is

a graduate veterinarian and is enrolled in the Department of Comparative Medicine’s 3-year laboratory animal medicine training program.

• The LACU began operations within the TriMetis animal facility on September 1, 2017. Groups of animals from the TSRB, Coleman and Wittenborg were moved to housing rooms in TriMetis which freed up space in these other facilities.

• A new supervisor, Tyler Patterson, started on September 25, 2017. Tyler supervises LACU operations in the TriMetis animal facility.

• UTHSC was visited by AAALAC in November 2017 as part of our re-accreditation. All aspects of the UTHSC Animal Care Program, including all animal facilities, were evaluated by the site visitors. The visitors were laudatory of the UTHSC Program, and spoke particularly well of the many LACU technicians with whom they interacted. There were no mandatory findings and continued full accreditation was recommended to AAALAC Council by the site visitors.

• The LACU veterinary team began regularly scheduled hands-on training classes for the campus in January 2018. Two different hands-on labs are offered: one in basic rodent techniques and one in aseptic surgical technique. A total of 10 rodent technique and 8 aseptic technique laboratories have been held since January 2018 for a total of 55 research staff trained.

• The LACU continued with its goal of technician training and education leading to certification by the American Association for Laboratory Animal Science (AALAS). At the end of FY18, 94% of husbandry technicians are now AALAS certified. In addition, a number of cage wash technicians have also obtained certification.

• The LACU core supported numerous publications, abstract presentations and extramural and intramural awards. A total of 132 manuscripts were published in which animal work was conducted on the UTHSC campus.

• The LACU continued its mission of education by participating in coursework related to animals in research, orienting new faculty and staff to the animal care facilities, and providing hands-on training to laboratory personnel.

8


Financial overview:

TOTALS FY17 FY18 Revenues* 2,805,431 2,351,047 Expenses** 3,401,871 3,874,369 Income (Subsidy) (596,349) (1,523,322) Equipment*** 0 72,000 Net Income (Subsidy) (596,349) (1,595,322) State Appropriation 590,429 715,209 Net Income (Subsidy) (5,920) (880,113) Other Expense (Caging)*** 0 550,952 Net Income (Subsidy) 0 (1,431,065) Subsidy, % before State Appropriation

17.53% 47.7%

Subsidy, % after State Appropriation

0.17% 31.8%

*Decreased revenues in FY18 resulted from the departure of several major users on campus, including Dr. Guy Reed, Dr. Stephania Cormier, Dr. Christopher Waters and Dr. Inna Gladysheva, and reduced revenues from external users, including the VA and RxBio (a commercial vendor). **Increased expenses were due to the transition of nine temporary employees to full-time staff, the hiring of Stanley Latocha, LATg (Director of Operations) and of Casey Inman, LATg (Assistant Operations Director, QA Manager), and repairs, renovations and increased supply expenses related to the 2018 AAALAC accreditation site visit by AALAS. ***In FY18, equipment costs were $72,000 and funding for the total costs of the purchase of new and replacement animal caging ($550,952) was split 50/50 between the VC for Research fund and UTHSC.

7. Suggested outcomes: It is recommended that the LACU continue as an institutional core.

9


Laboratory Animal Care Unit (LACU) Institutional Core Facility Summary of Institutional Core Activities for FY18 Written by David Hamilton, DVM; Jacqueline E. Toney; and Tiffany N. Seagroves, PhD

I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018)Full-length published articles (UTHSC faculty investigators are indicated in boldfont)

1. Concentrated Conditioned Media from Adipose Tissue Derived Mesenchymal StemCells Mitigates Visual Deficits and Retinal Inflammation Following Mild TraumaticBrain Injury. Jha KA, Pentecost M, Lenin R, Klaic L, Elshaer SL, Gentry J, Russell JM,Beland A, Reiner A, Jotterand V, Sohl N, Gangaraju R. Int J Mol Sci. 2018 Jul11;19(7). pii: E2016.

2. Effect of early embryonic deletion of huntingtin from pyramidal neurons on thedevelopment and long-term survival of neurons in cerebral cortex and striatum.Dragatsis I, Dietrich P, Ren H, Deng YP, Del Mar N, Wang HB, Johnson IM, JonesKR, Reiner A. Neurobiol Dis. 2018 Mar;111:102-117.

3. Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury ArePartially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189.Liu Y, McAfee SS, Guley NM, Del Mar N, Bu W, Heldt SA, Honig MG, Moore BM2nd, Reiner A, Heck DH. eNeuro. 2017 Aug 18;4(4). pii: ENEURO.0387-16.2017.

4. Disrupted striatal neuron inputs and outputs in Huntington’s disease. Deng, Y.P. & A.Reiner. CNS Neuroscience & Therapeutics. 2018 Apr;24(4):250-280.

5. Neural control of choroidal blood flow. Reiner, A., M.E.C. Fitzgerald, N. Del Mar & C.Li. Prog Retin Eye Res. 2018 May;64:96-130.

6. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminalchemosensory neurons to ethanol and its flavor components. Glendinning JI, Tang J,Morales Allende AP3 Bryant BP, Youngentob L, Youngentob SL. J Neurophysiol.2017 Aug 1;118(2):1198-1209.

7. A recurrent de novo missense mutation in UBTF causes developmentalneuroregression. Toro C, Hori RT, Malicdan MCV, Tifft CJ, Goldstein A, Gahl WA,Adams DR, Harper F, Wolfe LA, Xiao J, Khan MM, Tian J, Hope KA, Reiter LT,Tremblay MG, Moss T, Franks AL, Balak C; C4RCD Research Group, LeDoux MS.Hum Mol Genet. 2018 Feb 15;27(4):691-705.

8. DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice. Khan MM,Xiao J, Patel D, LeDoux MS. Neurobiol Aging. 2018 Feb;62:180-190.

9. Changes in potassium channel modulation may underlie afterhyperpolarizationplasticity in oxytocin neurons during late pregnancy. Wang L, Chandaka GK,

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Foehring RC, Callaway JC, Armstrong WE. J Neurophysiol. 2018 May 1;119(5):1745-1752.

10. Phosphatidylinositol 4,5-bisphosphate (PIP2) modulates afterhyperpolarizations inoxytocin neurons of the supraoptic nucleus. Kirchner MK, Foehring RC, Wang L,Chandaka GK, Callaway JC, Armstrong WE. J Physiol. 2017 Jul 15;595(14):4927-4946.

11. Functional Roles of Kv1-mediated Currents in Genetically-Identified Subtypes ofPyramidal Neurons in Layer 5 of Mouse Somatosensory Cortex. Guan D, Pathak D,Foehring RC. J Neurophysiol. 2018 Apr 11.

12. Brain Cytosolic Phospholipase A2α Mediates Angiotensin II-Induced Hypertensionand Reactive Oxygen Species Production in Male Mice. Song CY, Khan NS, Liao FF,Wang B, Shin JS, Bonventre JV, Malik KU. Am J Hypertens. 2018 Apr 13;31(5):622-629.

13. In vivo evidence for the contribution of peripheral circulating inflammatory exosomesto neuroinflammation. Li JJ, Wang B, Kodali MC, Chen C, Kim E, Patters BJ, Lan L,Kumar S, Wang X, Yue J, Liao FF. J Neuroinflammation. 2018 Jan 8;15(1):8.

14. Bidirectional interplay of HSF1 degradation and UPR activation promotes tauhyperphosphorylation. Kim E, Sakata K, Liao FF. PLoS Genet. 2017 Jul5;13(7):e1006849. doi: 10.1371/journal.pgen.1006849. eCollection 2017 Jul.

15. Hsp90 inhibitor induces nuclear translocation of HSF1 predominantly in hippocampalCA1 region. Wang B, Liu Y, Huang L, Chen J, Li JJ, Wang R, Kim E, Chen Y, JusticiaC, Sakata K, Chen H, Planas A, Ostrom RS, Li W, Yang G, McDonald MP, Chen R,Heck DH, Liao FF. Mol Psychiatry. 2017 Jul;22(7):935.

16. A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss inAPP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.Wang B, Liu Y, Huang L, Chen J, Li JJ, Wang R, Kim E, Chen Y, Justicia C, SakataK, Chen H, Planas A, Ostrom RS, Li W, Yang G, McDonald MP, Chen R, Heck DH,Liao FF. Mol Psychiatry. 2017 Jul;22(7):990-1001.

17. Does pathology of small venules contribute to cerebral microinfarcts and dementia?Hartmann DA, Hyacinth HI, Liao FF, Shih AY. J Neurochem. 2018 Mar;144(5):517-526.

18. Olfactory bulb acetylcholine release dishabituates odor responses and reinstates odorinvestigation. Ogg MC, Ross JM, Bendahmane M, Fletcher ML. Nat Commun. 2018May 14;9(1):1868.

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19. Overlapping Representation of Primary Tastes in a Defined Region of the GustatoryCortex. Fletcher ML, Ogg MC, Lu L, Ogg RJ, Boughter JD Jr. J Neurosci. 2017 Aug9;37(32):7595-7605.

20. Does prolonged severe hypercapnia interfere with normal cerebrovascular function inpiglets? Pourcyrous M, Chilakala S, Elabiad MT, Parfenova H, Leffler CW. PediatrRes. 2018 May 28. doi: 10.1038/s41390-018-0061-5.

21. Preventing harmful effects of epileptic seizures on cerebrovascular functions innewborn pigs: does sex matter? Liu J, Pourcyrous M, Fedinec AL, Leffler CW,Parfenova H. Pediatr Res. 2017 Nov;82(5):881-887.

22. Lactobacillus plantarum prevents and mitigates alcohol-induced disruption of colonicepithelial tight junctions, endotoxemia, and liver damage by an EGF receptor-dependent mechanism. Shukla PK, Meena AS, Manda B, Gomes-Solecki M, DietrichP, Dragatsis I, Rao R. FASEB J. 2018 Jun 18:fj201800351R. doi:10.1096/fj.201800351R.

23. Recombinant E. coli Dualistic Role as an Antigen-adjuvant Delivery Vehicle for OralImmunization. Gomes-Solecki M, Richer L. Methods Mol Biol. 2018;1690:347-357.doi: 10.1007/978-1-4939-7383-5_27.

24. Pre-treatment with Lactobacillus plantarum prevents severe pathogenesis in miceinfected with Leptospira interrogans and may be associated with recruitment ofmyeloid cells. Potula HH, Richer L, Werts C, Gomes-Solecki M. PLoS Negl Trop Dis.2017 Aug 25;11(8):e0005870.

25. Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of RapidlyAdapting Mechanoreceptor Ascending Axons. Kridsada K, Niu J, Haldipur P, Wang Z,Ding L, Li JJ, Lindgren AG, Herrera E, Thomas GM, Chizhikov VV, Millen KJ, Luo W.Cell Rep. 2018 Jun 5;23(10):2928-2941.

26. Wilhelm His' lasting insights into hindbrain and cranial ganglia development andevolution. Glover JC, Elliott KL, Erives A, Chizhikov VV, Fritzsch B. Dev Biol. 2018Feb 12. pii: S0012-1606.

27. Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial CellDamage after Renal Ischemia-Reperfusion Injury. Pressly JD, Mustafa SM, Adibi AH,Alghamdi S, Pandey P, Roy KK, Doerksen RJ, Moore BM Jr, Park F. J PharmacolExp Ther. 2018 Feb;364(2):287-299. doi: 10.1124/jpet.117.245522. Epub 2017 Nov29.

28. A Potent, Metabolically Stable Tubulin Inhibitor Targets the Colchicine Binding Siteand Overcomes Taxane Resistance. Arnst KE, Wang Y, Hwang DJ, Xue Y, CostelloT, Hamilton D, Chen Q, Yang J, Park F, Dalton JT, Miller DD, Li W. Cancer Res.2018 Jan 1;78(1):265-277.

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29. Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177Phosphorylation. Zhai X, Leo MD, Jaggar JH. Circ Res. 2017 Sep 1;121(6):650-661.

30. Calcium- and voltage-gated BK channels in vascular smooth muscle. Dopico AM,Bukiya AN, Jaggar JH. Pflugers Arch. 2018 May 11.

31. Elevated plasma catecholamines functionally compensate for the reduced myogenictone in smooth muscle STIM1 knockout mice but with deleterious cardiac effects.Pichavaram P, Yin W, Evanson KW, Jaggar JH, Mancarella S. Cardiovasc Res. 2018Apr 1;114(5):668-678.

32. Trafficking of BK channel subunits controls arterial contractility. Leo MD, Jaggar JH.Oncotarget. 2017 Nov 3;8(63):106149-106150.

33. Cerebellar Purkinje Cells Generate Highly Correlated Spontaneous Slow-RateFluctuations. Cao Y, Liu Y, Jaeger D, Heck DH. Front Neural Circuits. 2017 Sep20;11:67. doi: 10.3389/fncir.2017.00067.

34. Hippocampal sharp-wave ripples in awake mice are entrained by respiration. Liu Y,McAfee SS, Heck DH. Sci Rep. 2017 Aug 21;7(1):8950.

35. Rhythms of the Body, Rhythms of the Brain: Respiration, Neural Oscillations, andEmbodied Cognition. Varga S, Heck DH. Consciousness and Cognition. 2017 56, 77-90.

36. Robust Transmission of Rate Coding in the Inhibitory Purkinje Cell to CerebellarNuclei Pathway in Awake Mice. Abbasi S, Hudson AE, Maran SK, Cao Y, Abbasi A,Heck DH, Jaeger D. Plos Computational Biology 2017 13(6): e1005578.

37. Breathing as a fundamental rhythm of brain function. Heck DH, McAfee SS, Liu Y,Babajani-Feremi A, Rezaie R, Freeman WJ, Wheless, J.W., Papanicolaou AC,Ruszinko M, Sokolov Y, Kozma R. Frontiers in Neural Circuits, 2017 10:115.

38. Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stemcells against hydrogen-peroxide-induced oxidative stress. Bhatti FUR, Kim SJ, Yi AK,Hasty KA, Cho H. Cell Tissue Res. 2018 Jun 27. doi: 10.1007/s00441-018-2857-3.

39. The role of Syk in peripheral T cells. Park JE, Majumdar S, Brand DD, Rosloniec EF,Yi AK, Stuart JM, Kang AH, Myers LK. Clin Immunol. 2018 Jul;192:50-57.

40. The Role of Leukocyte-Associated Ig-like Receptor-1 in Suppressing Collagen-Induced Arthritis. Kim S, Easterling ER, Price LC, Smith SL, Coligan JE, Park JE,Brand DD, Rosloniec EF, Stuart JM, Kang AH, Myers LK. J Immunol. 2017 Oct15;199(8):2692-2700.

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41. Genetic control of oromotor phenotypes: A survey of licking and ingestive behaviorsin highly diverse strains of mice. St John SJ, Lu L, Williams RW, Saputra J, BoughterJD Jr. Physiol Behav. 2017 Aug 1;177:34-43.

42. Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotectionafter stroke. Ismael S, Zhao L, Nasoohi S, Ishrat T. Sci Rep. 2018 Apr 13;8(1):5971.

43. MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like ReceptorProtein-3 Inflammasome, Protects Mice against Traumatic Brain Injury. Ismael S,Nasoohi S, Ishrat T. J Neurotrauma. 2018 Jun 1;35(11):1294-1303.

44. Adenosine A1 receptor-operated calcium entry in renal afferent arterioles isdependent on postnatal maturation of TRPC3 channels. Soni H, Peixoto-Neves D,Buddington RK, Adebiyi A. Am J Physiol Renal Physiol. 2017 Dec 1;313(6):F1216-F1222.

45. TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs. SoniH, Peixoto-Neves D, Matthews AT, Adebiyi A. Am J Physiol Renal Physiol. 2017 Nov1;313(5):F1136-F1148.

46. Early septic insult in neonatal pigs increases serum and urinary soluble Fas ligandand decreases kidney function without inducing significant renal apoptosis. Soni H,Adebiyi A. Ren Fail. 2017 Nov;39(1):83-91.

47. Cisplatin-induced oxidative stress stimulates renal Fas ligand shedding. Soni H,Kaminski D, Gangaraju R, Adebiyi A. Renal Failure. 2018; 40:314-322.

48. The effects of type I interferon on glioblastoma cancer stem cells. Du Z, Cai C, SimsM, Boop FA, Davidoff AM, Pfeffer LM. Biochem Biophys Res Commun. 2017 Sep16;491(2):343-348.

49. Unphosphorylated STAT3 regulates the antiproliferative, antiviral, and gene-inducingactions of type I interferons. Pfeffer SR, Fan M, Du Z, Yang CH, Pfeffer LM. BiochemBiophys Res Commun. 2017 Aug 26;490(3):739-745.

50. Androgen receptor agonists increase lean mass, improve cardiopulmonary functionsand extend survival in preclinical models of Duchenne muscular dystrophy.Ponnusamy S, Sullivan RD, You D, Zafar N, He Yang C, Thiyagarajan T, JohnsonDL, Barrett ML, Koehler NJ, Star M, Stephenson EJ, Bridges D, Cormier SA, PfefferLM, Narayanan R. Hum Mol Genet. 2017 Jul 1;26(13):2526-2540.

51. Noncalcemic 20-hydroxyvitamin D3 inhibits human melanoma growth in in vitro andin vivo models. Skobowiat C, Oak AS, Kim TK, Yang CH, Pfeffer LM, Tuckey RC,Slominski AT. Oncotarget. 2017 Feb 7;8(6):9823-9834.

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52. MiRNA203 suppresses the expression of protumorigenic STAT1 in glioblastoma toinhibit tumorigenesis.Yang CH, Wang Y, Sims M, Cai C, He P, Yue J, Cheng J, BoopFA, Pfeffer SR, Pfeffer LM. Oncotarget. 2016 Dec 20;7(51):84017-84029.

53. SMARCE1 regulates metastatic potential of breast cancer cells through theHIF1A/PTK2 pathway. Sethuraman A, Brown M, Seagroves TN, Wu ZH, Pfeffer LM,Fan M. Breast Cancer Res. 2016 Aug 5;18(1):81.

54. The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction in glioma.Ganguly D, Fan M, Yang CH, Zbytek B, Finkelstein D, Roussel MF, Pfeffer LM.Oncotarget 2018 9:22095-112.

55. Pivotal role for the ESCRT-II complex subunit EAP30/SNF8 in IRF3-dependent innateantiviral defense. Kumthip K, Yang D, Li NL, Zhang Y, Fan M, Sethuraman A, Li K.PLoS Pathog. 2017 Oct 30;13(10):e1006713.

56. Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits,bilateral thalamic calcification, and altered brain iron homeostasis. Dietrich P, JohnsonIM, Alli S, Dragatsis I. PLoS Genet. 2017 Jul 17;13(7):e1006846.

57. Potential effect on molecular pathways in different targeted genes in the VEGF familyin retina - From the genomic point of view. Cui J, Liu L, Lu H, Wei D, Jiao Y, JablonskiMM, Williams RW, Gu W, Chen H. Exp Eye Res. 2018 Jun 23;176:78-87.

58. Retina Compatible Interactions and Effective Modulation of Blood Ocular Barrier P-gpActivity by Third-Generation Inhibitors Improve the Ocular Penetration of Loperamide.Janga KY, Tatke A, Shukla S, Lamichhane SP, Avula B, Wang X, Jablonski MM,Khan IA, Majumdar S. J Pharm Sci. 2018 Aug;107(8):2128-2135.

59. P-glycoprotein Restricts Ocular Penetration of Loperamide across the Blood-OcularBarriers: a Comparative Study in Mdr1a Knock-out and Wild Type Sprague DawleyRats. Tatke A, Janga KY, Avula B, Wang X, Jablonski MM, Khan IA, Majumdar S.AAPS PharmSciTech. 2018 May;19(4):1662-1671.

60. Ion-sensitive in situ hydrogels of natamycin bilosomes for enhanced and prolongedocular pharmacotherapy: in vitro permeability, cytotoxicity and in vivo evaluation.Janga KY, Tatke A, Balguri SP, Lamichanne SP, Ibrahim MM, Maria DN, JablonskiMM, Majumdar S. Artif Cells Nanomed Biotechnol. 2018 Feb 23:1-12.

61. Isolation of Primary Murine Retinal Ganglion Cells (RGCs) by Flow Cytometry.Chintalapudi SR, Patel NN, Goldsmith ZK, Djenderedjian L, Wang XD, Marion TN,Jablonski MM, Morales-Tirado VM. J Vis Exp. 2017 Jul 5;(125).

62. Water-soluble Complex of Curcumin with Cyclodextrins: Enhanced PhysicalProperties For Ocular Drug Delivery. Maria DN, Mishra SR, Wang L, Abd-Elgawad

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AH, Soliman OA, El-Dahan MS, Jablonski MM. Curr Drug Deliv. 2017 Sep 6;14(6):875-886.

63. Destroying the androgen receptor (AR)-potential strategy to treat advanced prostatecancer. Narayanan R, Ponnusamy S, Miller DD. Oncoscience. 2017 Dec 28;4(11-12):175-177.

64. Novel Selective Agents for the Degradation of Androgen Receptor Variants to TreatCastration-Resistant Prostate Cancer. Ponnusamy S, Coss CC, Thiyagarajan T,Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G,Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, NarayananR. Cancer Res. 2017 Nov 15;77(22):6282-6298.

65. GATA4 Directly Regulates Runx2 Expression and Osteoblast Differentiation. KhalidAB, Slayden AV, Kumpati J, Perry CD, Osuna MAL, Arroyo SR, Miranda-CarboniGA, Krum SA. JBMR Plus. 2018 Mar;2(2):81-91.

66. GATA4 represses RANKL via multiple long-range enhancers to regulate osteoclastdifferentiation. Khalid AB, Slayden AV, Kumpati J, Perry CD, Berryhill SB, CrawfordJA, Fatima I, Morselli M, Pellegrini M, Miranda-Carboni GA, Krum SA. Bone. 2018Jul 19. pii: S8756-3282(18)30279-5.

67. Estrogens and selective estrogen receptor modulators differentially antagonize Runx2in ST2 mesenchymal progenitor cells. Amzaleg Y, Ji J, Kittivanichkul D, E TörnqvistA, Windahl S, Sabag E, Khalid AB, Sternberg H, West M, Katzenellenbogen JA, KrumSA, Chimge NO, Schones DE, Gabet Y, Ohlsson C, Frenkel B. J Steroid Biochem MolBiol. 2018 May 8. pii: S0960-0760.

68. The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibitsproliferation and EMT in human triple-negative breast cancer. Fatima I, El-Ayachi I,Taotao L, Lillo MA, Krutilina R, Seagroves TN, Radaszkiewicz TW, Hutnan M, BryjaV, Krum SA, Rivas F, Miranda-Carboni GA. PLoS One. 2017 Dec27;12(12):e0189864.

69. The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligaseregulate in vivo ligase function. Chen H, Sirupangi T, Wu ZH, Johnson DL, LaribeeRN. Sci Rep. 2018 May 25;8(1):8163.

70. MiR-181 family-specific behavior in different cancers: a meta-analysis view. Pop-BicaC, Pintea S, Cojocneanu-Petric R, Del Sal G, Piazza S, Wu ZH, Alencar AJ, LossosIS, Berindan-Neagoe I, Calin GA. Cancer Metastasis Rev. 2018 Mar;37(1):17-32.

71. Integrating Genetic and Gene Co-expression Analysis Identifies Gene NetworksInvolved in Alcohol and Stress Responses. Luo J, Xu P, Cao P, Wan H, Lv X, Xu S,Wang G, Cook MN, Jones BC, Lu L, Wang X. Front Mol Neurosci. 2018 Apr 5;11:102.

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72. The genetic dissection of Myo7a gene expression in the retinas of BXD mice. Lu Y,Zhou D, King R, Zhu S, Simpson CL, Jones BC, Zhang W, Geisert EE, Lu L. Mol Vis.2018 Feb 2;24:115-126.

73. Marine microalgae bioengineered Schizochytrium sp. Meal hydrolysates inhibits acuteinflammation. Wang X, Wang H, Pierre JF, Wang S, Huang H, Zhang J, Liang S, ZengQ, Zhang C, Huang M, Ruan C, Lin J, Li H. Sci Rep.2018 Jun; 8(1): 9848.

74. Bacterial translocation is required for pre-leukemic myeloproliferation in Tet2 deficientmice. Meisel M, Hinterleitner R, Pacis A, Chen L, Earley Z, Mayassi T, Pierre JF,Ernest J, Galipeau H, Thuille N, Bouziat, Buscarlet M, Ringus DL, Wang Y, Li Y, DinhV, Kim S, McDonald B, Zurenski MA, Musch M, Furtado GC, Lira S, Baier G, ChangEB, Erin A, Weber C, Busque L, Godley L, Verdu E, Barrerio LB, Jabri B. Nature, 2018May.

75. Deletion of Choline Acetyltransferase in enteric neurons results in intestinal dysmotilityand dysbiosis. Johnson CD, Barlow AJ, Pierre JF, Erickson CS, Epstein ML, GosainA. FASEB J.2018 Mar 23. PMID: 29570391.

76. Essential role of small bowel microbiota in regulating host digestive and absorptiveadaptive responses to dietary lipids. Martinez-Guryn K, Frazier K, Hubert N, Urlass S,Musch MA, Ojeda P, Pierre JF, Sontag T, Reardon C, Leone V, Chang EB. Cell Host& Microbe, 2018. 23(4):458-469.

77. Antioxidant Micronutrients Alter Mucosal Inflammatory Risk in a Murine Model ofGenetic and Microbial Susceptibility. Pierre JF, Hinterleitner R, Bouziat R, Hubert N,Leone V, Miyoshi J, Jabri B, Chang EB. Journal of Nutritional Biochemistry, 2017 Dec10;54:95-104.

78. A Neonatal Murine Model of MRSA Pneumonia. Fitzpatrick, E. A., D. You, B.Shrestha, D. Siefker, V. S. Patel, N. Yadav, S. Jaligama, and S. A. Cormier. 2017.,PLoS One, 12: e0169273.

79. Radical containing combustion derived particulate matter enhance pulmonary Th17inflammation via the aryl hydrocarbon receptor. Jaligama, S., V. S. Patel, P. Wang, A.Sallam, J. Harding, M. Kelley, S. R. Mancuso, T. R. Dugas, and S. A. Cormier. 2018.,Part Fibre Toxicol, 15: 20.

80. Regulatory T cells and IL10 suppress pulmonary host defense during early-lifeexposure to radical containing combustion derived ultrafine particulate matter.Jaligama, S., J. Saravia, D. You, N. Yadav, G. I. Lee, B. Shrestha, and S. A. Cormier.2017., Respir Res, 18: 15.

81. Androgen receptor agonists increase lean mass, improve cardiopulmonary functionsand extend survival in preclinical models of Duchenne muscular dystrophy.Ponnusamy, S., R. D. Sullivan, D. You, N. Zafar, C. He Yang, T. Thiyagarajan, D. L.

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Johnson, M. L. Barrett, N. J. Koehler, M. Star, E. J. Stephenson, D. Bridges, S. A. Cormier, L. M. Pfeffer, and R. Narayanan. 2017., Hum Mol Genet, 26: 2526-40.

82. IL-4Ralpha on dendritic cells in neonates and Th2 immunopathology in respiratorysyncytial virus infection. Shrestha, B., D. You, J. Saravia, D. T. Siefker, S. Jaligama,G. I. Lee, A. A. Sallam, J. N. Harding, and S. A. Cormier. 2017., J Leukoc Biol, 102:153-61.

83. Parturition in baboons (PAPIO SPP.). Schlabritz-Loutsevitch N, Maher J, Sullivan R,Mari G, Schenone M, Cohen HL, Word RA, Hubbard GB, Dick EJ Jr. Sci Rep. 2018Jan 19;8(1):1174.

84. Comprehensive Selection of Reference Genes for Quantitative RT-PCR Analysis ofMurine Extramedullary Hematopoiesis During Development. Medrano G, Guan P,Barlow-Anacker AJ, Gosain A. PLoS One. 2017 Jul; 12(7):e0181881.

85. Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity,reduced blood pressure and neointima formation. Zou Y, Chen Z, Jennings BL, ZhaoG, Gu Q, Bhattacharya A, Cui Y, Yu B, Malik KU, Yue J. Sci Rep. 2018 Jan23;8(1):1468.

86. MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependentinterferon response pathway. Yang CH, Wang Y, Sims M, Cai C, He P, Häcker H, YueJ, Cheng J, Boop FA, Pfeffer LM. Oncotarget. 2017 Dec 6;8(68):112980-112991.

87. A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulpand Dentin-Like Tissue. Zhu X, Liu J, Yu Z, Chen CA, Aksel H, Azim AA, Huang GT.Tissue Eng Part C Methods. 2018 Feb;24(2):108-120.

88. Human and Swine Dental Pulp Stem Cells Form a Vascular like Network afterAngiogenic Differentiation in Comparison with Endothelial Cells: A QuantitativeAnalysis. Aksel H, Huang GT. J Endod. 2017 Apr;43(4):588-595.

89. The effect of enriched environment across ages: A study of anhedonia and BDNFgene induction. Dong BE, Xue Y, Sakata K. Genes Brain Behav. 2018 May 2:e12485.

90. Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5,CHRM2, and CHRM5: effects of drug and environmental treatments. Sakata K,Overacre AE. J Neurochem. 2017 Oct;143(1):49-64.

91. Striatal but not extrastriatal dopamine receptors are critical to dopaminergic motorstimulation. Wang Y, Zhou FM. Front. Pharmacol. 2017, 8:935.

92. cAMP-producing chemogenetic activation of indirect pathway striatal projectionneurons and the downstream effects on the globus pallidus and subthalamic nucleusin freely moving mice. Bouabid S, Zhou FM. J Neurochem. 2018, 145(6):436-448.

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93. Phosphorylation hotspot in the C-terminal domain of occludin regulates the dynamicsof epithelial junctional complexes. Manda B, Mir H, Gangwar R, Meena AS, Amin S,Shukla PK, Dalal K, Suzuki T, Rao R. J Cell Sci. 2018 Apr 6;131(7). pii: jcs206789.

94. Fluorescence-Activated Cell Sorting of Murine Mammary Cancer Stem-Like CellSubpopulations with HIF Activity. Brooks DL, Seagroves TN. Methods Mol Biol.2018;1742:247-263.

95. Chromatin Immunoprecipitation of HIF-α in Breast Tumor Cells Using Wild Type andLoss of Function Models. Brooks DL, Seagroves TN. Methods Mol Biol.2018;1742:67-79.

96. Resolvin D1 blocks H2O2-mediated inhibitory crosstalk between SHP2 and PP2A andsuppresses endothelial-monocyte interactions. Chattopadhyay R, Mani AM, SinghNK, Rao GN. Free Radic Biol Med. 2018 Mar;117:119-131.

97. LIM and cysteine-rich domains 1 is required for thrombin-induced smooth muscle cellproliferation and promotes atherogenesis. Janjanam J, Zhang B, Mani AM, Singh NK,Traylor JG Jr, Orr AW, Rao GN. J Biol Chem. 2018 Mar 2;293(9):3088-3103.

98. Heterodimers of the transcriptional factors NFATc3 and FosB mediate tissue factorexpression for 15(S)-hydroxyeicosatetraenoic acid-induced monocyte trafficking.Kotla S, Singh NK, Kirchhofer D, Rao GN. J Biol Chem. 2017 Sep 8;292(36):14885-14901.

99. Unravelling the interplay of sphingolipids and TGF-β signaling in the human cornealstroma. Nicholas SE, Rowsey TG, Priyadarsini S, Mandal NA, Karamichos D. PLoSOne. 2017 Aug 14;12(8):e0182390.

100. Role of autotaxin in cancer stem cells. Lee D, Suh DS, Lee SC, Tigyi GJ, Kim JH.Cancer Metastasis Rev. 2018 Jun 20. doi: 10.1007/s10555-018-9745-x.

101. FoxO1 regulates myocardial glucose oxidation rates via transcriptional control ofpyruvate dehydrogenase kinase 4 expression. Gopal K, Saleme B, Al Batran R,Aburasayn H, Eshreif A, Ho KL, Ma WK, Almutairi M, Eaton F, Gandhi M, Park EA,Sutendra G, Ussher JR. Am J Physiol Heart Circ Physiol. 2017 Sep 1;313(3):H479-H490.

102. Secretory phospholipase A2 group IIA modulates insulin sensitivity andmetabolism. Kuefner MS, Pham K, Redd JR, Stephenson EJ, Harvey I, Deng X,Bridges D, Boilard E, Elam MB, Park EA. J Lipid Res. 2017 Sep;58(9):1822-1833.

103. Activation of human smooth muscle BK channels by hydrochlorotiazide requirescell integrity and the presence of BK β1 subunit. Martín P, Moncada M,Kuntamallappanavar G, Dopico, AM and Milesi V. Acta Pharmacol Sin. 2018Mar;39(3):371-381.

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104. The BK channel β1 subunit transmembrane domain 2 is necessary for this subunitto facilitate BK current inhibition by ethanol and subsequent cerebral arteryconstriction. Kuntamallappanavar G and Dopico AM. British J Pharmacol 2017 Dec174:4430-48.

105. The effect of prenatal alcohol exposure on fetal growth and cardiovascularparameters in a baboon model of pregnancy. Tobiasz A, Duncan J, Bursac Z, SullivanR, Tate D, Dopico AM, Bukiya A and Mari G. Reprod Sci. 2018 Jul;25(7):1116-1123.

106. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries viamodulation of ethanol-induced BK channel inhibition in vascular smooth muscle.Simakova M, Bisen S, Dopico AM and Bukiya A. Biochem Pharmacol. 2017 Dec1;145:81-93.

107. Different functional domains measured by cocaine self-administration under theprogressive-ratio and punishment schedules in male Wistar rats. Datta U, Martini M,Sun W. Psychopharmacology (Berl). 2018 Mar;235(3):897-907.

108. Sex Differences in the Motivational Contrast between Sucrose and Cocaine inRats. Datta U, Martini, Mariangela, Sun, WenLin. J Drug Des Res 2017 4(3): 1042.

109. Social learning promotes nicotine self-administration by facilitating the extinctionof conditioned aversion in isogenic strains of rats. Han W, Wang T, Chen H. Sci Rep.2017 Aug 14;7(1):8052.

110. Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibitadipogenesis. Xiao Z, Baudry J, Cao L, Huang J, Chen H, Yates CR, Li W, Dong B,Waters CM, Smith JC, Quarles LD. J Clin Invest. 2018 Jan 2;128(1):157-174.

111. Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated witha reduction in surfactant proteins. Schwingshackl A, Lopez B, Teng B, Luellen C,Lesage F, Belperio J, Olcese R, Waters CM. Am J Physiol Lung Cell Mol Physiol.2017 Dec 1;313(6):L1030-L1046.

112. Matrix Metalloproteinase-9 Mediates the Deleterious Effects of α2-Antiplasmin onBlood-Brain Barrier Breakdown and Ischemic Brain Injury in Experimental Stroke.Singh S, Houng AK, Reed GL. Neuroscience. 2018 Apr 15;376:40-47.

113. Enhanced heart failure, mortality and renin activation in female mice withexperimental dilated cardiomyopathy. Tripathi R, Sullivan R, Fan TM, Wang D, SunY, Reed GL, Gladysheva IP. PLoS One. 2017 Dec 14;12(12):e0189315.

114. Knockdown of survivin results in inhibition of epithelial to mesenchymal transitionin retinal pigment epithelial cells by attenuating the TGFβ pathway. Zhang P, Zhao G,Ji L, Yin J, Lu L, Li W, Zhou G, Chaum E, Yue J. Biochem Biophys Res Commun.2018 Apr 6;498(3):573-578.

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115. Chronic features of allergic asthma are enhanced in the absence of resistin-likemolecule-beta. LeMessurier KS, Palipane M, Tiwary M, Gavin B, Samarasinghe AE.Sci Rep. 2018 May 4;8(1):7061.

116. Saccharomyces cerevisiae-Derived Mannan Does Not Alter Immune Responsesto Aspergillus Allergens. Lew DB, LeMessurier KS, Palipane M, Lin Y, SamarasingheAE. Biomed Res Int. 2018 Jan 1;2018:3298378.

117. Humoral immune responses during asthma and influenza co-morbidity in mice.Doorley LA, LeMessurier KS, Iverson AR, Palipane M, Samarasinghe AE.Immunobiology. 2017 Dec;222(12):1064-1073.

118. Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on AllergicAsthma Mouse Models. Lew DB, Michael CF, Overbeck T, Robinson WS, RohmanEL, Lehman JM, Patel JK, Eiseman B, LeMessurier KS, Samarasinghe AE, GaberMW. J Immunol Res. 2017;2017:3432701.

119. IL23 and TGF-ß diminish macrophage associated metastasis in pancreaticcarcinoma. Hussain SM, Reed LF, Krasnick BA, Miranda-Carboni G, Fields RC, BiY, Elahi A, Ajidahun A, Dickson PV, Deneve JL, Hawkins WG, Shibata D, Glazer ES.Sci Rep. 2018 Apr 11;8(1):5808.

120. Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition.Chiu CQ, Martenson JS, Yamazaki M, Natsume R, Sakimura K, Tomita S, TavalinSJ, Higley MJ. Neuron. 2018 Jan 17;97(2):368-377.

121. Activation of Group II Metabotropic Glutamate Receptors Suppresses Excitabilityof Mouse Main Olfactory Bulb External Tufted and Mitral Cells. Dong HW, Ennis M.Front Cell Neurosci. 2018 Jan 17;11:436.

122. Synthesis and biological evaluation of indole-based UC-112 analogs as potent andselective survivin inhibitors. Wang Q, Arnst KE, Xue Y, Lei ZN, Ma D, Chen ZS, MillerDD, Li W. Eur J Med Chem. 2018 Apr 10;149:211-224.

123. Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization InhibitorsTargeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.Banerjee S, Arnst KE, Wang Y, Kumar G, Deng S, Yang L, Li GB, Yang J2 White SW,Li W, Miller DD. J Med Chem. 2018 Feb 22;61(4):1704-1718.

124. 1α,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structureand Route of Chemical Synthesis. Lin Z, Chen H, Belorusova AY, Bollinger JC, TangEKY, Janjetovic Z, Kim TK, Wu Z, Miller DD, Slominski AT, Postlethwaite AE, TuckeyRC, Rochel N, Li W. Sci Rep. 2017 Aug 31;7(1):10193.

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125. Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/DifferentiationFactor 3 in Adipose Tissue Macrophages. Bu Y, Okunishi K, Yogosawa S, Mizuno K,Irudayam MJ, Brown CW, Izumi T. Diabetes. 2018 Jun 26. pii: db171201. doi:10.2337/db17-1201.

126. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysisduring ageing. Camell CD, Sander J, Spadaro O, Lee A, Nguyen KY, Wing A,Goldberg EL, Youm YH, Brown CW, Elsworth J, Rodeheffer MS, Schultze JL, DixitVD. Nature. 2017 Oct 5;550(7674):119-123.

127. Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy. Chen H,Lin Z, Arnst KE, Miller DD, Li W. Molecules. 2017 Aug 1;22(8). pii: E1281.

128. The quinic acid derivative KZ-41 prevents glucose-induced caspase-3 activationin retinal endothelial cells through an IGF-1 receptor dependent mechanism. He H,Weir RL, Toutounchian JJ, Pagadala J, Steinle JJ, Baudry J, Miller DD, Yates CR.PLoS One. 2017 Aug 10;12(8):e0180808.

129. Janagam DR, Ananthula S, Chaudhry K, Wu LF, Mandrell TD, Johnson JR andLowe TL. Injectable In Situ Forming Depot Systems for Long-Acting Contraception.Advanced Biosystems. August 25, 2017. DOI:10.1002/adbi.201700097.

130. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelialto mesenchymal transition in ovarian cancer cells. Zhao G, Wang Q, Gu Q, Qiang W,Wei JJ, Dong P, Watari H, Li W, Yue J. Oncotarget. 2017 Oct 17;8(55):94666-94680.

131. New mouse model of pulmonary hypertension induced by respiratory syncytialvirus bronchiolitis. Kimura D, Saravia J, Jaligama S, McNamara I, Vu LD, Sullivan RD,Mancarella S, You D, Cormier SA. Am J Physiol Heart Circ Physiol. 2018 Jun 15.doi: 10.1152/ajpheart.00627.2017.

132. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocularpressure and glaucoma susceptibility. Chintalapudi SR, Maria D, Di Wang X, BaileyJNC; NEIGHBORHOOD consortium; International Glaucoma Genetics consortium,Hysi PG, Wiggs JL, Williams RW, Jablonski MM. Nat Commun. 2017 Nov24;8(1):1755.

II. PRESENTATIONS GIVEN TO PROMOTE CORE USAGEA. New Faculty Orientation

One of the LACU veterinarians attends each of the UTHSC new facultyorientation days and meets with investigators who plan to use animals as part of their research. Information is provided regarding LACU contact information, facility locations, services provided and a copy of the current LACU per diem rate sheet is distributed.

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B. CoursesCMED711 Essentials of Animal Experimentation – Department of ComparativeMedicine. This graduate course is offered every fall semester and 21 students enrolled in school year 2017-2018. The course is a requirement for the Laboratory Research and Management Program in the College of Graduate Health Sciences. The course involves didactic and hands on training and covers the animal species most commonly used in research. Students learn handling and common techniques for rats and mice and perform a practice surgery. They also receive a tour of one of the animal facilities, learn how to write an IACUC protocol and are given an introduction to the various regulations surrounding the use of animals in research.

C. Facility OrientationsThe Training Coordinator, Leadra Williford, conducts facility orientations andmeets with all new investigators and all new research staff prior to granting card access to an animal facility. This is generally the first introduction of new research staff to the LACU and allows us to become familiar with the lab’s research focus and offer expertise and training if necessary. The facility orientation consists of a PowerPoint presentation followed by a tour of the animal facility for the building in which the lab is located. The entire orientation lasts 1-1.5 hours and provides information on: • LACU contact information for each animal facility, including after hour phone

numbers• LACU services (e.g. animal ordering, animal imports, technical services)• Available equipment for research use (e.g. ultrasound machine, x-ray unit,

micro CT)• Rodent cage types and drinking water options• Animal facility traffic patterns• IACUC policies (e.g. animal transport, euthanasia, animal density)• LACU policies (e.g. personal protective equipment, animal ordering,

reporting sick animals, animal bites)• ACAP training and cage card printing

The orientation is followed by a tour of the facility by the supervisor where the research staff get to meet other members of the LACU, including the area supervisor and learn where to find equipment, store feed etc. Proper cage changing practices using microisolator technique are also demonstrated during the tour. At the end of the orientation, a copy of the presentation, along with the various policies and documents that were discussed during the orientation, are emailed to the individual.

For FY18, 27 orientations were provided with a total of 89 research staff trained.

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III. SUMMARY OF ACTIVITIES FOR FY18A. Personnel

In FY18, the LACU consisted of 42 permanent and 2 temporary staff members:• Director: Dr. David Hamilton, DVM (100%)• Clinical Veterinarian: Dr. Tyler Aycock (100% effort)• Post-Doctoral Veterinarians: (1) Dr. Cameron Fili• Operations Management: (2) Stanley Latocha (100% effort) and Casey

Inman (100% effort)• Administrative Staff:

Asst. Director/ LACU Business Mgr.: Jacqueline E. Toney (75% effort)Financial Coordinator: Joyce Jones (100% effort)Accounting Assistant: Chitora Jackson (100% effort)

• Supervisors:Husbandry: (3) Sherry Frazier (100% effort), Brad Stevens (100% effort)and Tyler Patterson (100% effort),

• Training Coordinator: Leadra Williford (100% effort)• Veterinary Technicians: (2) Stacey Barnett (83% effort) and Kadijah

Wainwright (100% effort)• Husbandry Technicians: 18 @ 100% effort• Cage Wash Technicians: 7 @ 100% effort• Service Assistants: 2 @ 100% effort• Service/Transportation Technician: 1 @ 100% effort• Temporary Service Assistants: 2 @ 100% effort

There were 5 buildings on campus which contain animal facilities: Cancer Research Building (CRB) Coleman Building Translational Sciences Research Building (TSRB) TriMetis Wittenborg Building

B. Oversight CommitteeThe Laboratory Animal Care Unit Internal Advisory Board (IAB) consists of thefollowing members for FY18: • Anton Reiner (Anatomy and Neurobiology, COM)• Anna Bukiya (Pharmacology, COM)• Megan Mulligan (Genetics, Genomics and Informatics, COM)• Jon Jaggar (Physiology, COM)• Amali Samarasinghe (Pediatrics, COM)• Kristen O’Connell (Physiology, COM)• Byron Jones (Genetics, Genomics and Informatics, COM), IAB CHAIR

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C. EquipmentEquipment currently housed in the LACU core for shared investigator use

Equipment Cost Funding Source

Date Purchased

VisualSonics Vevo 2100 ultrasound machine $400,013.00 J07002200 01/23/09

Starr MouseOx pulse oximeter $4,950.00 LACU Core 06/06/2008

Sedecal/Idexx X-ray machine $103,500.00 J07002200 01/25/2010

Anesthetic Machines (5) $25,000 LACU Core multiple

D. Service Contracts

Contract Title: Vendor: Payable Amount:

Automatic Watering System: Coleman, Wittenborg, TSRB & CRB

Edstrom Direct $13,258.00

VisualSonics Vevo 2100 ultrasound machine

Specialty Underwriters, LLC

$14,470.00

Maintenance Service Contract TSRB Facility

Getinge/Castle Inc.

$30,318.00

SHL Periodic Maintenance Service Agreement

Adam Stonaker/DBA Stonaker Hospital & Lab, LLC

$38,226

Tecniplast Service Agreement Equipment in TSRB

Tecniplast $71,194.00

TOTAL $167,466

E. Core Revenues by Department, FY18

Department Name Department ID

LACU Internal & External Amount

Physiology U070132013 $305,966.52 Genetics, Genomics & Informatics U070132039 $300,056.87 Pharmacology U070132011 $236,981.14 Anatomy and Neurobiology U070132006 $223,036.52 Neurology U070132080 $122,903.20 Ophthalmology U070132085 $117,457.21 Pediatrics-Cardiology U070120005 $97,636.50 Medicine-Nephrology U070133060 $93,727.56

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Pharmaceutical Sciences U070336020 $84,819.32 Pediatrics-Infectious Disease U070120055 $76,518.58 Pediatrics-Research U070120080 $68,270.15 Comparative Medicine U070139015 $67,506.56 Microbiology, Immunology & Biochemistry U070132009 $59,110.40 Pathology U070132099 $54,385.69 Pediatrics-Administration U070120001 $52,098.68 Pediatrics-Obesity U070120085 $51,246.53 Medicine-Rheumatology U070133030 $50,642.58 Pediatrics-Nephrology U070120065 $36,709.53 Orthopaedic Surgery U070132090 $36,127.93 Surgery-General U070132050 $35,638.21 Medicine-Hematology U070133065 $31,795.58 Vice Chancellor for Research U071701016 $24,278.23 Department of Clinical Pharmacy U070336050 $23,287.93 Medicine-Endocrinology U070133015 $18,802.65 Pediatrics-Genetics U070120040 $13,538.05 Obstetrics & Gynecology U070132025 $11,706.44 Medicine-Infectious Diseases U070133070 $10,476.70 GME Residents-Memphis U070132066 $9,681.21 Pediatrics-Neonatology U070120060 $7,154.23 Medicine-Internal Medicine U070133002 $6,988.70 Medicine-Cardiology U070133010 $6,529.08 Laboratory Animal Care Unit U071701055 $4,596.94 Bioscience Research U070234075 $3,060.36 Health Affairs & Govern Relations U071300150 $2,652.70 Nursing-Academic Programs U070538065 $1,808.56 Medicine-Gen Internal Med U070133003 $1,763.78 Pediatrics-Pulmonology U070120075 $1,658.27 Pediatrics-Immunology/Rheumatology U070120050 $298.71 Preventive Medicine U070132035 $129.20 No Department Assigned $0.00

$2,313,197

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F. Core Revenue from External Users, FY2018

Vendor: PI/Contact: Revenue: LeBonheur Schaller, Alexandra $7,173.75 LeBonheur Gosain, Ankush $4,454.64 LeBonheur You, Dahui $2,570.89 LeBonheur Khan, Sheema $2,607.57

Rhodes Jones, Joyce $222.30 VA Park, Edwards $1,641.89 VA Elam, Marshall $1,073.64

LeBonheur Stephenson, Erin $8,613.96 University of

Memphis Bumgardner, Joel $321.36

University of Memphis

Buddington, Randy $117.00

Oxford Immuotech Jones, Joyce $425.00 RxBIO Thompson, Karin $2,442.96

Trimetis Bares, Steven $1,587.34 VA Jones, Joyce $4,598.05

TOTAL $37,850.35

G. Multi-year trends

Mouse care days, total (all types of caging)

Year Care days Total revenues FY18 1,890,148 $1,648,515 FY17 2,151,345 $1,834,300 FY16 2,016,862 $1,729,493 FY15 1,922,137 $1,654,469 FY14 1,690,919 $1,421,870

Rat care days, total (all types of caging)

Year Care days Total revenues FY18 110,509 $154,825 FY17 121,415 $165,059 FY16 99,505 $135,720 FY15 81,042 $111,124 FY14 82,035 $108,181

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Rabbit care days

Year Care days Total revenues FY18 5,004 $9,655 FY17 5,803 $10,913 FY16 3,966 $7,767 FY15 0 $0 FY14 0 $0

Chicken care days

Year Care days Total revenues FY18 0 0 FY17 1,167 $8,076 FY16 3,289 $27,507 FY15 2,576 $21,789 FY14 7,746 $38,272

Pig care days

Year Care days Total revenues FY18 905 $7,425 FY17 993 $8,275 FY16 1,721 $15,536 FY15 3,530 $31,663 FY14 3,640 $31,215

Non-human primate care days

Year Care days Total revenues FY18 0 0 FY17 598 $5,908 FY16 459 $4,535 FY15 633 $6,254 FY14 106 $1,017

Total Service Fee Revenues

Year Total revenues FY18 $149,545 FY17 $229,062 FY16 $276,866 FY15 $261,828 FY14 $197,441

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Total LACU Animal and Supplies Orders Revenues

Year Total revenues FY18 $462,029 FY17 $577,395 FY16 $634,543 FY15 $511,110 FY14 $616,625

H. FY2018 Fee StructureLACU revenue is primarily generated through per diem rates and charges for special services. Animal housing is billed through a daily per diem charge, depending on the species, animal size and cage type. Management and veterinary staff submit charge tickets/material orders through the internal ACIM system to invoice for special services such as veterinary procedures, animal transport or equipment usage.

FY2018 PER DIEMS

SPECIES CAGING INTERNAL

RATE EXTERNAL

RATE

INTERNAL HAZARD /ABSL2

EXTERNAL HAZARD/

ABSL2 Cage $0.85 $1.11 $1.08 $1.40 Large Cage $1.38 $1.79 $1.38 $1.79

MICE Sterile/Microisolator $1.67 $2.17 $2.00 $2.60 Large Sterile/Microisolator $1.77 $2.30 $2.12 $2.76 RBL BCU Isolator Cage $2.12 $2.76 Cage $0.85 $1.11 $1.03 $1.34

PEROMYSCUS Large Cage $1.15 $1.50 $1.38 $1.79 Sterile/Microisolator $1.39 $1.81 $1.67 $2.17 Large Sterile/Microisolator $1.77 $2.30 $2.12 $2.76

RATS Cage $1.38 $1.79 $1.66 $2.16 Diabetic Cage $1.66 $2.61 -- --

HAMSTERS Cage $1.32 $1.72 -- -- Sterile/Microisolator $1.83 $2.38 -- --

GUINEA PIGS Cage $2.08 $2.70 $2.50 $3.25 Large Cage $6.10 $7.93 $7.32 $9.52

GERBILS Cage $1.32 $1.72 $1.58 $2.05 <2kg $1.84 $2.39 $2.21 $2.87

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RABBITS 2kg - 5.4kg $1.99 $2.59 $2.38 $3.09 > 5.4kg $2.09 $2.72 $2.51 $3.26

DOGS Single $8.14 $10.58 -- -- PRIMATES Rhesus -- -- $8.05 $10.47

Baboons -- -- $10.18 $13.23 SHEEP/GOATS $10.29 $13.38

-- --

Neonate $8.16 $10.61 -- -- SWINE < 25 lbs. $8.89 $11.56 -- --

25 lbs. - 75 lbs. $9.59 $12.47 -- -- > 75 lbs. $10.29 $13.38 -- -- Single $1.64 $2.13 -- -- Brooder $5.05 $6.57 -- --

CHICKENS Group 2-4 $4.14 $5.38 -- -- Group 5-10 $6.73 $8.75 -- -- Group >10 $9.28 $12.06 -- --

PIGEONS Single $1.64 $2.13 -- -- Group Up to 12 $9.28 $12.06 -- --

FROGS Tank $2.21 $2.87 -- -- FERRETS Single $6.36 $8.27 $7.85 $10.21

FY2018 LACU SERVICE FEES

SERVICE UT RATE EXTERNAL

RATE Airport Pickup/Order $61.80 $80.34 Feed & Bedding Delivery/Trip $61.80 $80.34 Special Animal Transport/Trip $61.80 $80.34 Veterinary Services/HR $77.25 $100.43 Technician Services/HR $38.63 $50.22

Facilities and Equipment Rodent Ultrasound/HR/Anesthesia/Day $41.20 $53.56 Radiography/Digital $30.90 $40.17 Surgery Room/HR/Sterile Surgery (includes instrument packs) $103.00 $133.90 Surgery Room/HR Non Sterile, No Instrument packs $51.50 $66.95 Gas Sterilization $30.90 $40.17 Steam Sterilization $30.90 $40.17 Gas Anesthesia Equipment/Use $41.20 $53.56 Cleaning Charge $46.35 $60.26

Purchasing Surcharges Drug & Supply Orders 15% 30% Animal Order Late Fee* (After 5pm on Tuesdays) 51.50 65.00

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IV. GRANTS THAT SUPPORTED THE CORE, FY18A. Active Awards• Smith, Amber

o NIH AI100946, Bacterial Virulence Factors• Smith, Amber

o NIH AI125324 Quantifying and Validating Dynamics for Influenza and Viral-Bacterial Pneomonias

• Samarasinghe, Amalio NIH AI125481, Eosinophils as Regulators of Host Immunity Again

Influenza Infections• Reiner, Anton

o Department of Defense W81XWH-16-1-0076, CB2 Receptor Therapy Using the FDA-Approved Drug Raloxifene to Mitigate Visual Deficits after Mild TBI and/or Ocular Trauma

• Foehring, Roberto NIH NS044163, Slowly Inactiviating K+ Channels in Neocortical Pyramidal

Cells• Heck, Detlef

o NIH NS091752, Effects of Traumatic Brain Injury on Temporal Dynamics of Brain Activity and Learning

• Youngentob, Steveno SUNY Binghamton Subcontract to NIG AA017823, Developmental

Exposure Alcohol Research Center• Boughter, John

o NIH DC015202, Taste Responses in Defined Cell Types in Custatory Cortex

• Armstrong, Williamo NIH HD072056, Reproductive Plasticity in Oxytocin Neurons

• Fletcher, Maxo NIH DC013779, Cholinergic Modulation of Olfactory Bulb Glomerular

Sensitivity• Hamre, Kristin

o NIH AA023508, Maternal Genotype: Choline Intervention; & Epigenetics in Fetal Alcohol Syndrome

• Kita, Hitoshio NIH NS057236, Synaptic Transmissions in the Basal Ganglia

• Ishrat, Tauheedo NIH NS097800, Mechanisms and Therapeutic Targets of Neurovascular

Injury in Hyperglycemic Stroke• Reiner, Anton

o NIH NS098137, Neural Control of Choroidal Blood Flow• Chizhikov, Viktor

o NIH NS093009, Mesenchymal-Neuroepithelial Interactions in the Developing Telencephalon

• Reiner, Antono NIH EY005298, Neural Control of Choroidal Blood Flow

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• Heck, Detlefo NIH MH112143, Neuronal Mechanisms of Cerebellar Cognitive Function

• Hori, Rodericko NIH GM118962, The Role of UBTF in Undiagnosed Neurodevelopmental

Disorders• Yi, Ae-kyung

o NIH AR064723, TLR/IL-1R Signaling Intermediaries and a Target-SpecificTherapeutic for Arthritis

• Radic, Markoo Lupus Research Institute, CD19-Targeted Cytotoxic T Cells for Lupus

Therapy• Jonsson, Colleen

o NIH AI103053, Evolutionary Mechanisms of RNA Virus Host Switching• Zhou, Fuming

o NIH NS085380, Ion Channel Mechanisms of Striatal Dopaminergic MotorStimulation

• Dopico, Alejandroo NIH HL104631, Vasodilation via Selective Pharmacological Targeting of

BK Channel Beta1 Subunits• Malik, Kafait

o NIH HL079109, Ecosanoids-Induced Vascular Growth During Injury• Tavalin, Steven

o NIH NS076637, Mechanisms Controlling AMPA Receptor SubunitComposition

• Sakata, Kazukoo NIH MH105567, Neural Mechanisms of Inflexible Learning Caused by

BDNF Deficiency• Liao, Francesca-Fang

o NIH NS091593, Endothelial ENOS-Deficient Mice as Chronic CerebralHypoperfusion Model

• Malik, Kafaito NIH HL019134, Angiotensins, Prostaglandins-Adrenergic Interactions

• Liao, Francesca-Fango Alzheimer's Association ZEN-16-362441, Neural Mechanisms of Inflexible

Learning Caused by BDNF Deficiency• Bukiya, Anna

o NIH AA023764, Cholesterol Control of Alcohol-Induced Cerebral ArteryConstriction

• Liao, Francesca-Fango NIH AG049772, Is HSF1 the Key in Mediating HSP90 Inhibitor Effect in

AD?• Zhou, Fuming

o NIH NS097671, Ion Channel Mechanisms of Striatal Dopaminergic MotorStimulation

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• Sun, Wen Lino NIH DA034776, Cocaine Addiction: Neuropharmacological Mechanisms of

Compulsive Cocaine Use• Dopico, Alejandro

o NIH AA011560, Ethanol Actions on SLO Channels from Arteries vs. Brain• Chen, Hao

o UCSD Subcontract to NIH DA 037844, Integrated GWAS of ComplexBehavioral and Gene Expression Traits in Outbred Rats

• Gadiparthi, Raoo NIH HL064165, Eicosanoids and Vascular Wall Remodeling

• Dragatsis, Ioanniso Dysautonomia Foundation Grant, Characterization of an FD Mouse Model

and Testing of Compounds that increase IKAP Expression• Jaggar, Jonathan

o NIH HL067061, Vascular Control by K+ Channel Trafficking• Parfenova, Elena

o NIH HL034059, Control of Neonatal Circulation• Tigyi, Gabor

o Columbia University Subcontract to NIH AI 067773, Mitigation ofRadiation-Induced Intestinal Barrier Damage by Radioprotectin-1

• Rao, Radhakrishnao NIH DK055532, Intestinal Mucosal Protection by Epidermal Growth Factor

• Waters, Christophero NIH HL131526, ASK1 and Ventilator-Induced Lung Injury

• Mancarella, Salvatoreo NIH HL114869, STIM-Dependent Signaling in Cardiac Pathophysiology

• Leo, Marie Denniso American Heart Association Grant 15SDG22680019, Regulation of

Arterial Contractility by Beta1 Subunit Trafficking• Bulley, Simon

o American Heart Association Grant 16SDG27460007, Role of TRPP2Channels in the Regulation of Arterial Contractility

• Leffler, Charleso NIH HL042851, Hydrogen Sulfide in Newborn Cerebral Circulation

• Jaggar, Jonathano NIH HL133256, Blood Pressure Regulation by Smooth Muscle Cell Ion

Channels• Gadiparthi, Rao

o NIH EY014856, Mechanisms of Retinal Angiogenesis• Gadiparthi, Rao

o NIH HL074860, Lipid Mediators and Vascular Diseases• Waters, Christopher

o NIH HL123540, CXCR4 Signaling in Lung Epithelial Repair• Gadiparthi, Rao

o NIH HL069908, NFATs and Vascular Injury

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• Tigyi, Gaboro NIH AI107331, IND-Enabling Pre-clinical Development of a Radiomitigator

• Adebiyi, Adebowaleo NIH DK101668, Regulation of Neonatal Renal Hemodynamics

• Parfenova, Elenao NIH NS101717, Astrocyte Functions in Neonatal Brain

• Gadiparthi, Raoo NIH HL103575, GPCR Signaling and Vascular Wall Remodeling

• Jaggar, Jonathano NIH HL137745, Endothelial Cell Potassium Channels

• Adebiyi, Adebowaleo American Heart Association Grant 16GRNT30990069, Myogenic Renal

Autoregulation in Neonatal Acute Kidney Injury• Dragatsis, Ioannis

o NIH ES028429, Genetic Modulators of 3-NP Neurotoxicity• Tigyi, Gabor

o NIH CA092160, Anticancer Strategies Targeting the Autotaxin-ReceptorAxis

• Bissler, Johno Department of Defense W81XWH-14-1-0343, Prevention of TSC Renal

Disease• Cormier, Stephania

o LSU Subcontract to NIH ES013648-Proj 2, LSU Superfund ResearchCenter - Environmentally Persistent Free Radicals

• Cormier, Stephaniao NIH AI090059, Regulation and Function of IL-33 During Neonatal RSV

Infection• Cormier, Stephania

o LSU Subcontract to NIH AI112402, Metabolic Approaches to Treat SevereViral and Inflammatory Diseases

• Cormier, Stephaniao NIH ES015050, Combustion Generated Particulate Pollution Affects Infant

Respiratory Health• Zhang, Weiqiang

o NIH HL123535, Characterization of an Inhibitory Protein Complex forCystic Fibrosis Therapy

• Mozhui, Khyobenio NIH AG055841, DNA Methylation and Gene Expression Study of Aging

and Lifespan Differences• Jones, Byron

o NIH AA021951, Genetics of Chronic Mild Stress and Alcohol Consumption• Jones, Byron

o NIH ES022614, Neural Toxicity of Paraquat is Related to Iron Regulationin the Midbrain

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• Williams, Roberto NIH AG043930, Translational Systems Genetics of Mitochondria,

Metabolism and Aging• Jones, Byron

o Department of Defense W81XWH-17-1-0472, Genetic Basis of IndividualDifferences in Susceptibility to Gulf War Illness

• Gosain, Ankusho NIH DK098271, Gastrointestinal Mucosal Immune Defects in

Hirschsprung’s Disease• Gosain, Ankush

o NIH DK114543, Validating Intestinal Enteroids to Study Hirschsprung’sAssociated Enterocolitis

• Ledoux, Marko NIH NS082296, Genetics and Biology of CIZ1 in Cervical Dystonia

• McDonald, Michaelo NIH AG054562 , Effects of Glycomacropeptide on Memory and Alzheimer-

Related Neuropathology• McDonald, Michael

o NIH NS094595, Effects of Modified Erythropoietin on Cognition andNeuropathology

• McDonald, Michaelo NIH AG051032, Effects of Intracranial rAAV.NEU3 on Dementia and

Neuropathology• Ledoux, Mark

o Department of Defense W81XWH-17-1-006, DNA Repair in Dystonia• Ledoux, Mark

o NIH NS094965, Pathophysiology of Paroxysmal Dyskinesias• Ledoux, Mark

o NIH NS101485, Mouse Models of Paroxysmal Non-KinesigenicDyskinesia

• Chaum, Edwardo Shulsky Foundation Grant, Phenotype Modeling and Therapeutic

Approaches to MELAS• Jablonski, Monica

o William &Ella Owens Medical Research Foundation, RetinalInflammasomes Mediate Ganglion Cell Death in Glaucoma

• Mandal, Nawajeso NIH EY022071, Sphingolipid Metabolism and Signaling in the Retina

• Gangaraju, Raja Shekharo Department of Defense W81XWH-16-1-0778, Adipose-Derived Stem Cells

Alleviate Visual Deficits in Blast Injury• Gangaraju, Raja Shekhar

o NIH EY023427, Vascular and Neuronal Repair with Adipose Stromal Cellsin Retinopathy

35


• Jablonski, Monicao University of Mississippi Subcontract to NIH EY022120, Evaluation and

Inhibition of Efflux Pumps Expressed on the Blood Ocular Barrier.• Jablonski, Monica

o Tisbury Pharmaceuticals, Dutch Belted Rabbit Efficacy/Tolerability Model• Jablonski, Monica

o Glaucoma Research Foundation, Extended Release IOP-LoweringFormulation

• Gu, Weikuano First Hospital of Qiqihaer Agreement, Collaboration Agreement with First

Hospital of Qiqihaer City in China/ First Hospital of Qiqihaer Agreement• Cho, Hongsik

o Arthritis Foundation, Novel Method of Detecting and Treating in Early PT,Using Smart Nanosone

• Miranda, Susano NIH AR064354, Determining the Mechanism of How GATA4 Directs ER-

Alpha Binding in Osteoblasts• Wu, Zhaohui

o American Cancer Society Grant RSG-13-186-01-CSM, Role of GenotoxicNF-kB Activation in Breast Cancer Metastasis

• Seagroves, Tiffanyo METAvivor Research Foundation, Targeting Creatine Kinases to Inhibit

Metastatic Breast Cancer (MBC)• Seagroves, Tiffany

o Department of Defense Grant W81XWH-16-1-0061, Targeting CreatineKinase, Brain Isoform (CKB) to Inhibit Metastatic Breast Cancer (MBC)

• Yue, Junmingo American Heart Association Grant 15GRNT25000015, Role of miR27b in

Vascular Wall Remodeling• Seagroves, Tiffany

o Univ Minnesota Subcontract to CA192178, Inducible PTK6 ExpressionDrives Oncogenic Signaling in Breast Cancer

• Fan, Meiyuno NIH CA197206, MYC/mIR-18A-5P/HIF1A Regulatory Network Confers

Drug Resistance to Breast Cancer• Reed, Guy

o NIH NS089707, Alpha-2-Antiplasmic and Ischemic Stroke• Gladysheva, Inna

o NIH HL115036, Corin in Cardiomyopathy and Heart Failure• Wang, Dong

o American Heart Association Grant 14SDG20510068, The Corin-ANP Axisin Myocardial Infarction and Ischemic Cardiomyopathy

• Dokun, Ayotundeo NIH HL130399, Modulation of mIR-29A and ADAM12 to Improve Arterial

Disease Outcomes in Diabetes

36


• Brand, Davido ETSU Subcontract to NIH AR068787, C-reactive protein in Rheumatoid

Arthritis• Quarles, Leigh

o NIH AR045955, Regulation and Function of FGF23• Quarles, Leigh

o NIH AR073518, Polycystins/TAZ as a Novel Therapeutic Target to TreatOsteoporosis

• Dale, Jameso NIH AI116808, Group A Streptococcal Vaccine Containing Immunogenic

Peptides of Streptolysin S• Dale, James

o NIH AI132117, Structure-Based Design of a Broadly Protective Group AStreptococcal Vaccine

• Huang, Georgeo Lehigh University Subcontract IIP-1602057, Preclinical Evaluation of

Bioactive Tailored Amorphous Multiporous (TAMP) Powder for theTreatment of Dentin Hypersensitivity

• Chauhan, Subhasho Department of Defense W81XWH-14-1-0154, A Novel Therapeutic

Modality for Advanced State Prostate Cancer Treatment• Chauhan, Subhash

o NIH CA162106, Etiology of Cervical Cancer Health Disparity in AmericanIndian Women

• Giorgianni, Francescoo NIH EY022706, Autoimmunity and Age-Related Macular Degeneration

• Li, Weio NIH CA148706, Targeting the Colchicine Site in Tubulin for Advanced

Melanoma• Yallapu, Murali

o NIH CA174841, PSMA Targeted Docetaxel Loaded MagneticNanoparticles for Prostate Cancer Therapy

• Chauhan, Subhasho NIH CA210192, Targeted Nanotherapy for Pancreatic Cancer

• Chauhan, Subhasho NIH CA206069, Development of Targeted Nanotechnology Platform for

Pancreatic Cancer• Meibohm, Bernd

o St Jude Subcontract to AI111449-Meibohm, Development ofAminospectinomycins for Biodefense

• Meibohm, Berndo Colorado State University Subcontract to NIH AI120670, Aerosol

Spectinamide-1599 Therapy Against Tuberculosis• Lowe, Tao

o NIH EY023853, Nanogels for Drug Delivery Across the BBB to TreatDiabetic Retinopathy

37


• Peters, Briano LSUHSC Subcontract to NIH AI 116025, Host and Microbial Factors

Promoting Synergistic Mortality During Polymicrobial Intra-abdominalInfections with Candida albicans and Staphylococcus aureus

• Peters, Briano NIH AI110541, A Novel Role for the Inflammasome in the

Immunopathogenesis of Candida Vaginitis• Palmer, Glen

o NIH AI099080, Molecular and Chemical Validation of the Vacuole as aNew Antifungal Target

• Gosain, Ankusho American College of Surgeons Research Award, Gastrointestinal Mucosal

Immune Defects in Hirschsprung’s Disease/American College of Surgeons

B. Pending GrantsPending grant proposals were not tracked in FY18.

V. BUSINESS DEVELOPMENT SUMMARYA. Market Assessment

Business in the LACU has decreased this year, despite an increase in the numberof investigators on campus who use animals. There was a net increase of 3principal investigators in FY18. We also saw an increase in the use of commonequipment, particularly the VisualSonics Vevo 2100 ultrasound machine and in thenumber of requests for veterinary technician assistance with research projects.The Nash animal facility was closed Summer 2017 with animals being moved intothe renovated Wittenborg vivarium. UTHSC assumed regulatory oversight of theTriMetis animal facility in September 2017, with LACU providing operational andveterinary oversight. Standard operating procedures were created and finalized forall operational and clinical functions within the LACU. These SOPs are used by theTraining Coordinator to standardize the level of animal care and evaluation acrosscampus. This has led to an increased attention to sanitization and disinfectionthroughout the animal facilities, increasing the quality of animal care and servicesoffered by the LACU. A new clinical veterinarian, Dr. Tyler Aycock, was hired inJune 2017, providing veterinary oversight of the Coleman, Wittenborg and TriMetisfacilities. A new supervisor, Tyler Patterson, was hired September 2017 andprovides oversight to the TriMetis facility. Along with the new hires in the LACU,the revised training provided to the staff will result in increasing productivity andefficiency and lead to better quality research data.

B. Competitive AnalysisLACU is the only core on the UTHSC campus that provides animal researchservices. Of all animal research cores in the Memphis area, we are the primaryone which can offer services to outside entities, particularly with regards to largeanimal surgical projects. We already do collaborative work with the Memphis VA,the University of Memphis, Le Bonheur Children’s Hospital and St. Jude Children’sResearch Hospital. We offer very competitive pricing and per diem rates and a

38


flexibility with regards to resources that does not exist with other animal research service providers in the area. We have an established working relationship with the Medical Education and Research Institute in Memphis, which provides fluoroscopic equipment available for use in specialized cardiovascular studies. We also created a working relationship with the University of Alabama at Birmingham transgenic core so that UTHSC investigators are charged UAB prices for transgenic mouse creation. We also provide dedicated transport of the transgenic mice from UAB so that they do not require quarantine upon arrival at UTHSC, thus saving investigators valuable time and research dollars.

C. Marketing Plans to Obtain New BusinessMost of our customers hear about our services through word of mouth from otherinvestigators who have utilized services provided by LACU. For investigators oncampus, or new to the UTHSC campus, much of the information about the coreand its services are relayed either through word-of-mouth, during new facultyorientations or though the facility orientations as outlined in section II. A one-pageLACU brochure was recently created through the Office of Research and is nowavailable for download through the Office of Research “Research Resources”webpage or direct from the LACU website. This brochure will now be distributed tonew faculty and research staff as part their orientation to the campus or animalfacility. The LACU now has a core brochure and updated webpage that highlightsthe level of expertise present within the core and the various services available toinvestigators. The LACU created a list serve email which is used to notifyinvestigators of changes in procedures and policies and is also used to advertisenew or updated services as they become available. In January 2018, The LACUbegan publishing a quarterly newsletter which is distributed to all research labs oncampus via email and is posted on the LACU Website. Each Newsletter highlightspersonnel changes within the LACU, research-relevant clinical SOPs and othernews and procedures throughout the facilities.

D. Forecasted Volumes for New BusinessIt is difficult to forecast volumes for new business, as most researchers do notprovide advance notice of their projects. We expect an overall increase in thenumber of animals used on campus. Although we expect work using large animals(pigs, non-human primates, etc.) to decrease, the increased volume of work usingrodents should offset this change. LACU has purchased 4 new low-flow anesthesiainstruments (SomnoSuite), which are available to research laboratories for use ona daily fee basis. Work with the VisualSonics Vevo 2100 ultrasound machine isexpected to remain strong and to further increase in the next fiscal year as otherinvestigators realize the power in this imaging modality. Dr. Zhongjie Sun joinedUTHSC as the new Chair in Physiology in 2018 and plans to hire 5+ new principalinvestigators, the majority of which are expected to be rodent users.

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VI. BudgetFY18 Actual Budget (July 1, 2017- June 30, 2018)

FY2018 DEBITS CREDITS Salaries/Fringe Benefits* $2,138,364 Supplies $1,171,535 Service Contracts $167,466 Equipment (> $5,000) $72,000 Other Expenses** $397,004 TOTAL EXPENSES $3,946,369 FY18 Internal Recoveries $2,313,197 FY18 External Recoveries $37,850 TOTAL CREDITS $2,351,047 Income / (Subsidy) ($1,595,322) State Appropriation*** $715,209 Income / (Subsidy) ($880,113) Caging*** $550,952 Net Income / (Subsidy) ($1,431,065)

*Salaries and fringe benefits includes the use of temporary employees, $88,333.

**Other expenses include travel, media/communications, maintenance/repairs, memberships, copier rental and registration fees ($397,004).

***Funding for the total costs of the purchase of new and replacement animal caging ($550,952) was split 50/50 between the VC for Research and UTHSC. Therefore, the total expenses for the core, including caging, were $4,497,321.

Subsidy before State appropriation, including caging: 47.7% ($2,146,274) Subsidy after State appropriation, including caging: 31.8% ($1,431,065)

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Research Biocontainment Laboratory (RBL)

Research Biocontainment Laboratory (RBL) Institutional Research Core Facility Analysis Report- FY18 Written by Colleen Jonsson, PhD; Jacqueline E. Toney; and Tiffany N. Seagroves, PhD

1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The RBL core designation as an institutional core is appropriate since it served 7 departments and 2 Colleges (COM and COP). 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. In FY18, this core processed projects from 12 unique users across 7 departments. 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. 4. Can the services for the core be outsourced more economically? No. It should also be noted that most BSL2 and BSL3 work requires specialized handling and SOPs and, therefore, must be processed locally. The RBL is the only facility available to UTHSC or external users in the Memphis area that has the appropriate engineering controls, facilities and resources for BSL3/ABSL3 research. 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led to at least 6 PubMed-indexed publications and supported several extramural grants and awarded intramural grants or startup funding packages. Services available in the RBL are unique and essential for investigators to maintain their research programs on BSL3/ABSL3 infectious or select agents. Overall, the RBL enhances UTHSC’s ability to compete for research projects in virology, bacterial pathogenesis, bacterial generated toxins and immunology, with a focus on emerging infectious diseases and select agents. 6. Is the core currently self-sufficient, or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution. After the State appropriation, the net subsidy was 25.7%. Accomplishments this past year:

• Hired RBL Director, Colleen Jonsson (July 2017) to revamp the existing RBL program to be more robust and provide targeted services for ABSL2 and ABSL3 studies. She also created the new Institute for the Study of Host Pathogen Systems.

• Created a new marketing strategy to enhance, promote and increase the in vivo and after life studies performed in the RBL, thus creating more collaborative partnerships with internal, external, commercial and government agencies.

• Created a new RBL Program Manager position to support the studies within the RBL, promote new partnerships and develop and manage the grant and contract

41

Research Biocontainment Laboratory (RBL)

proposal process. Also created 2 new Sr. Research Specialist positions to assist with use of specialized RBL equipment and research studies.

• Reorganized 5 laboratories to better utilize the space and equipment. • Completed training on high-end research equipment and updated and made

functional the Luminex 200 and the Janus Robots. Other new equipment were made available to augment services, including the EnVision multimode plate reader, the MAGPIX multiplexing protein detection system, the QuantStudio real-time PCR instrument, an Illumina MiSeq, the BiotekFX instrument and a blood analyzer to support Clinical Chemistry & Hematology services.

• Added 19 new personnel to the RBL Select Agent Registration. • Developed operational SOPs for a new animal model (ferrets) and conducted

hands-on training for husbandry and vet staff. • Worked with external and internal personnel to develop and roll out iLab software

for RBL scheduling and billing. This will allow us to more accurately track facility and equipment usage.

• RBL held its first corporate retreat that consisted of Management and Staff employees. It enabled us to enhance effectiveness by allowing time for strategic planning and outlined goals for the department. A few of our topics included: Growth & Opportunities; Advancement & Promotion; Staff Development & Infrastructure needs.

Financial overview:

TOTALS FY17 FY18 Revenues 221,535 130,680 Expenses (746,642) (1,170,295) Income (Subsidy) (525,107) (1,039,615) Other Costs (38,156) 0 Income (Subsidy) (563,263) (1,039,165) State Appropriation 627,204 737,969 Net Income (Subsidy) 63,941 (301,646) Subsidy, % before State Appropriation

75% 89%


-- 25.7%

Subsidy, prior to State appropriation: 89% ($1,039,165) Subsidy, after State appropriation: 25.7% ($301,646)

7. Suggested outcomes: It is recommended that RBL continue as an institutional core.

42

Regional Biocontainment Laboratory (RBL)

Regional Biocontainment Laboratory (RBL) Institutional Core Facility Summary of Institutional Core Activities for FY18 Written by Colleen Jonsson, PhD; Jennifer Stabenow, MS; Jayne McKinnie; Jacqueline Toney; and Tiffany N. Seagroves, PhD I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018) Full length published articles (UTHSC faculty investigators are indicated in bold font)

1. Lee, D., Suh, D.S., Lee, S.L., Tigyi, G.J*. and Kim, J.H.* (2018) Role of Autotaxin in Cancer Stem Cells. Cancer Metastasis & Reviews. May 2018 2018 Jun 20. PMID: 29926310

2. Novel FR-900493 Analogs that Inhibit Outgrowth of Clostridium difficile Spores. Mitachi, K.; Yun, H-G.; Kurosu, S. M.; Eslamimehr, S.; Lemieux, M. R.; Klaić, L.; Clemons, W. M.; Kurosu, M. ACS Omega. 2018 Feb 28, 3(2): 1726-1739. PMID: 29503973.

3. Inhibition of N-Glycosylation towards Novel Anti-Cancer Chemotherapeutics, Kurosu, M. J. Mol. Pharmaceutics Org. Process Res. 2018, 6(1): pii:141. PMID: 30417028.

4. Loss of Upc2p-Inducible ERG3 Transcription Is Sufficient to Confer Niche-Specific

Azole Resistance without Compromising Candida albicans Pathogenicity. Luna-Tapia A, Willems HME, Parker JE, Tournu H, Barker KS, Nishimoto AT, Rogers PD, Kelly SL, Peters BM, Palmer GE. MBio. 2018 May 22;9(3). PMID: 29789366.

5. Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Richardson JP, Willems HME, Moyes DL, Shoaie S, Barker KS, Tan SL, Palmer GE, Hube B, Naglik JR, Peters BM. Infect Immun. 2017 Nov 6. pii: IAI.00645-17. PMID: 29109176.

6. Overexpression of Candida albicans Secreted Aspartyl Proteinases 2 or 5 is not sufficient for exacerbation of immunopathology in a murine model of vaginitis. Willems HME, Bruner WS, Barker KS, Liu J, Palmer GE, Peters BM. Infect Immun. 2017 Jul 31. pii: IAI.00248-17. PMID: 28760935,

Patents:

1. Glycosyltransferase inhibitors for treatment of solid tumors. Kurosu, M.; Clemons, Clemons, W. M. Serial Number: 62/616,657, Filed: 1/12/2018 CIT File Number: 7939-P

2. Pleuromutilin derivatives and uses thereof. Kurosu, M.; Mitachi, K. filed: February

2017, Serial No.: 62/460,400

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II. PRESENTATIONS GIVEN TO PROMOTE CORE USAGE:

Date Name Affiliation

11/13/2017 Drs. Mildred Randolph, Robin Mulkey, Christy

Simecka

U. of Arkansas Medical Center

11/30/2017 Dr. A. Hoffman UCLA

12/11/2017 Dr. Clemons UTHSC

01/11/2018 Dr. Cheoyang Xue Rutgers

03/08/2018 Dr. Karyl Buddington U. of Memphis

03/14/2018 Dr. Brianne Hibl Baylor

04/23/2018 Dr. Matt Lawrenz U. of Louisville

06/12/2018 Dr. Rudra Channapporavey U. of Iowa

06/26/2018 Special Agent Erica Cottingham FBI

III. SUMMARY OF ACTIVITIES A. Personnel

Director: Colleen Jonsson (7% RBL salary/ 7% RBL effort) Facility Manager: Jennifer Stabenow (100% RBL salary/ effort) Building Superintendent: Rob Benson (100% RBL salary/ effort) Supervisor (ABSL-3): Lillian Zalduondo (100% RBL salary/ effort) Asst. Building Superintendent: Chris Sears (100% RBL salary/ effort) RBL Equipment Specialist: John Burns (100% RBL salary/ effort) Sr. Research Specialist: Jyothi Parvathareddy (100% RBL salary/ effort) Sr. Lab Animal Care Technician: Fu Zeng (100% RBL salary/ effort) Lab Animal Care Technician: Crystal Murphy (100% RBL salary/ effort) Cage Wash Tech: LaDarion White (100% RBL salary/ effort)

44


Asst. Director/ RBL Business Mgr.: Jacqueline Toney (25%RBL salary/ 25% RBL effort) Administrative Coordinator II: Jayne McKinnie (100% RBL salary/ effort)

B. Oversight Committee: University of Tennessee RBL Executive Committee (UTREC)

UTREC consists of the following members: Steven Youngentob, Ph.D. (Sr. Associate Vice Chancellor for Research, Dept. of Anatomy and Neurobiology) UTREC Chair Michael Whitt, Ph.D. (Dept. of Microbiology, Immunology & Biochemistry) Mark Miller, Ph.D. (Dept. of Microbiology, Immunology & Biochemistry) Jennifer Stabenow. M.S., R.V.T. (RBL) Robert Benson (RBL) Tiffany Seagroves, Ph.D. (Associate Vice Chancellor for Research-Core Facilities, and Dept. of Pathology and Laboratory Medicine) David Hamilton. D.V.M. (Lab Animal Care Unit) Jayne McKinnie (RBL) Jacqueline Toney (RBL)

C. Equipment

Responsible cost center:

Equipment Description: Cost: Capitalized on:

E070165001 FACS Aria II Special order system 367,940.00 01/21/2009 E070165001 IVIS Spectrum Imaging System 344,708.00 12/11/2008 E070165 JANUS Intergrator Platform 225,952.00 01/06/2010

E070165 Delta Vision personal DV Live Cell Imaging System 191,598.76 09/14/2009

E070165 MiSeq System 95,931.00 07/16/2018 E070165 CH Technologies BANG unit 92,690.00 05/11/2010

E070165 Minidox-M Chlorine Dioxide Gas Generator 75,158.92 09/02/2009

E070165 En Vision Multilabel Reader 69,825.00 06/11/2010 E070165 EnVision Multilabel Reader 67,620.00 01/06/2010 E070165 CH Technologies BANG unit 63,965.40 07/21/2010 E070165 Millipore Luminex 200 3.1 x Ponent 45,591.00 12/21/2009 E070165 MDT Disposable Tip Head 44,700.00 07/24/2018

E070165001 BioPROtect lll Bio-Containment Enclosure for BD 44,400.00 05/08/2009

E070165 BCU 2000 Housing System for Mice 41,350.00 02/10/2012 E070165 BCU 2000 Housing System for Mice 41,350.00 02/10/2012

E070165002 QSTUDIO 6 FLX, 384W INST, ;PTP 1 SYSTEM 38,844.78 12/20/2017

E070165 CFX96 Realtime PCR Detection System 35,900.00 11/16/2009

E070165001 Cage Mouse Bio-Containment Unit #1 30,068.21 12/10/2008

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E070165001 Synergy 2 SLFA Model Plate Reader 28,630.50 03/30/2009 E070165 Synergy 2 SLFA Model Dr. Byrne 28,630.50 10/15/2009 E070165 42-Cage mouse Bio containment unit 27,098.46 09/02/2010 E070165 42-Cage mouse Bio containment unit 27,098.46 09/02/2010 E070165 42-Cage mouse Bio containment unit 27,098.46 09/02/2010 E070165002 MAGPIX with XPONENT 4.2 23,660.00 11/13/2017 E070165 Synergy HT RDR - (Miller) 23,605.00 09/18/2006 E070165 DiaSys Chemistry System Analyzer 22,696.99 04/23/2018

E070165 42-Cage Bio containment unit w/ blower and battery 22,364.50 06/19/2012

E070165002 MAGPIX with XPONENT 4.2 19,472.79 09/02/2010 E070165002 Multiflo Fx with Peri Washer 19,472.79 09/02/2010

E070165 softWoRx Computer Server 3.7.0 (Linux) 19,163.95 01/13/2010

E070165001 Eddy Jet Automatic Plater for Spiral Spreading 18,954.00 09/12/2008

E070165 2014 POLARIS GEM TRUCK 18,192.32 01/16/2014 E070165002 Infinite M200 PRO # Monochromator 16,234.00 06/18/2014 E070165001 Ventilated Animal Transport Unit 13,812.60 05/14/2009 E070165001 Axiovert 40 cfl 11,865.00 06/22/2009 E070165 Axiovert 40 CFL 11,865.00 07/14/2009 E070165002 ULT FZ TSX60086A 115V/60HZ PMO 11,367.20 05/01/2018 E070165 Upright -86 Ultralow Freezer 11,034.00 05/05/2017 E070165002 Fastprep-24 Instruemt Homogenizer 10,950.00 08/09/2013 E070165 DiaSys Hematology Analyzer 10,849.04 04/23/2018

E070165 ATI Model 2HA Digital Photometer 120V w/attachment 10,547.83 02/19/2010

E070165001 Revco -80 Eltplus 21cf 208 V 9,915.00 03/19/2009 E070165002 Nuaire Upright -85 C 24CF 220V 9,153.00 09/21/2017 E070165001 Axiocam mrm rev.3 w/firewi dir 9,079.00 06/30/2009 E070165001 Flash and Go Colony Counter 8,912.70 09/12/2008 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Legend XTR CF14 Centrifuge 8,820.00 06/30/2010 E070165 Nuaire Class II Type A2 BSC 8,449.00 06/06/2018 E070165 Nuaire Upright -85 C 17.1cf 220V 8,275.00 09/29/2017 E070165 Nuaire Upright -85 C 17CF 220V 8,275.00 10/13/2017 E070165 Nuaire Upright -85 C 17CF 220V 8,275.00 01/11/2018

E070165 Upright -85 C 17.1 CF 220V Upright Freezer 8,275.00 05/22/2018

E070165 Nuaire Upright -85 17.1 220v 8,275.00 07/16/2018 E070165 -86C 11cf Ultra low vlu 12 dir 8,149.18 06/30/2010 E070165 -86C 11cf Ultra low vlu 12 dir 8,149.18 06/30/2010

46


E070165 Upright -86 Ultralow Freezer 8,013.00 03/12/2018 E070165002 Nuaire 540-400 Clean Air Cabinet 7,921.00 02/05/2018 E070165 Autoclave Trolley rat unit 7,913.76 03/29/2011 E070165001 Revco -80 slimline 11cuft - 208V 1of 8 7,630.04 03/23/2009 E070165001 Revco -80 slimline 11cuft - 208V 7of 8 7,630.04 03/26/2009 E070165001 Revco -80 slimline 11cuft - 208V 4of 8 7,630.04 03/26/2009

E070165001 Revco -80 slimline 11cuft - 208V 5 of 8 7,630.04 03/26/2009

E070165001 TC 28/28 Legend Centrifuge promo pkg 6,945.98 03/19/2009

E070165001 Legend RT+ centrifuge promo pkg 1 of 4 6,945.98 03/23/2009




E070165 BCUAT1000-42 (BCU Autoclave trolley mouse 6,417.84 09/16/2011

E070165 BCUAT1000-42 (BCU Autoclave trolley mouse 6,417.84 09/16/2011

E070165 Autoclave Trolley mouse 6,399.91 10/19/2010 E070165 Autoclave Trolley mouse 6,398.93 09/02/2010 E070165 Autoclave Trolley mouse 6,398.92 09/02/2010 E070165 Autoclave Trolley mouse 6,398.92 01/19/2011

E070165 Nuaire Nu-425-300 Clean Air Cabinet Class 125 6,329.00 09/02/2009

E070165001 Legend RT Centri Touch 230V 1 OF 2 6,324.00 03/26/2009

E070165 Dell OptiPlex 7010N Minitower/windows 7 6,285.00 08/04/2014

E070165 Model 2H Digital Photometer 120V 6,226.25 07/19/2011 E070165001 Shaker E24R W Univ. Plat #2 5,954.50 02/09/2009 E070165001 Shaker E24R W Univ. Plat #3 5,954.50 02/09/2009 E070165001 Shaker E24R W Univ. Plat #4 5,954.50 02/09/2009 E070165001 Shaker E24R W Univ. Plat #5 5,954.50 02/09/2009 E070165001 Shaker E24R W Univ. Plat #1 5,954.50 02/09/2009 E070165 Universal Cage And Pan Wash Cart 5,539.42 01/13/2012 E070165001 GE -20 Freezer 5,235.00 03/26/2009 E070165001 Revco Chrom Ref 29.2 cuft 5,235.00 05/08/2009 E070165001 Revco Chrom Ref 29.2 cuft 5,235.00 05/08/2009 E070165001 Revco Chrom Ref 29.2 cuft 5,235.00 05/08/2009

E070165 Regan Blower Part BLW-RGN-001 w/Mix Box part # MB 5,075.84 11/02/2010

E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010

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E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010 E070165 Napco 8000DH CO2 Incubator 5,023.45 06/30/2010

D. RBL Service Contracts Vendor Equipment Cost/yr. Cytek Bioscience* FACSAria II sorter $20,554 *replaced BD Biosciences vendor service in 2018

Siemens PM for access control security $35,466

Specialty Underwriters Luminex, EnVision, and IVIS Spectrum $53,684 Total costs, all service contracts

$109,704 E. Advertisement of the Core RBL participated in the FY18 new faculty orientation sponsored by the Office of Academic, Faculty and Student Affairs event, provided tours to distinguished guests, prospective users and new laboratory staff and participated in the Hot Topics seminar series. F. Usage Volumes

BSL-2/3 Space Rental: Internal: 32 total mos. rented (combined all PIs) External academic: 0 total mos. rented (combined all users) Commercial: 0 total mos. rented (combined all users) ABSL-2/3 space rental: Internal: 66 total mos. rented (combined all PIs) External academic: 0 total mos. rented (combined all users) Commercial: 0 total mos. rented (combined all users)

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FACSAriaII: Operator assisted: no usage External academic: no usage Commercial: no usage BANG (aerosol infection device): Operator assisted: no usage External, academic: no usage Commercial: no usage DeltaVision fluorescent microscope: Unassisted: no usage Operator assisted: no usage External academic: no usage Commercial: no usage IVIS Spectrum Bio-Imager *: Unassisted: no usage Operator assisted: no usage External academic: no usage Commercial: no usage Luminex: Unassisted: 1 user Operator assisted: no usage External academic: no usage Commercial: no usage Janus high-throughput robot: Unassisted: no usage Operator assisted: no usage External academic: no usage Commercial: no usage qPCR: Unassisted: no usage Operator assisted: no usage External academic: no usage Commercial: no usage

Overall usage of the RBL Core: Internal, UTHSC clients: 7 Departments

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RBL Core Revenues by PI, FY18

Investigator Department/College Amount Ying Kong MIB, COM $14,637 (ABSL2/3)

Anders Sjostedt MIB, COM $3,433 (ABSL2/3)

Santosh Kumar/Ted Cory

Pharmacology, COM $10,300 (BSL2/3)

Charles Yates Pharmaceutical Sciences, COP $60 (Luminex)

Glen Palmer Clinical, Pharmacy COP $20,624 (ABSL2)

Bernd Meibohm Pharmaceutical Sciences, COP $7,725 (BSL2/3)

Michio Kurosu Pharmaceutical Sciences, COP $11,133 (BSL2/3)

Mark Miller MIB, COM $10,950 (ABSL2/3)

Byron Jones MIB, COM $16,435 (ABSL2/3)

Gabor Tigyi Physiology, COM $8,265 (ABSL2/3)

Amber Smith Nursing COM $9,564 (ABSL2/3)

Brian Peters Clinical, Pharmacy, COP $17,423 (ABSL2/3)

Total: $130,549

G. Training Offered to Core Users

Type of Training # of Training Sessions

# of Attendees

Hands-On-Training 18 45 Initial RBL/Select Agent Training 7 19 Annual RBL/Select Agent Training 4 40 Campus Police Training 2 5 Equipment Training - Envision Plate Reader - QuantStudio 6 - DiaSys Hematology &Chemistry Analyzer

1 1 1

12 6 5

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H. FY18 Fee Structure

PPE-Room Charges*:

ABSL2 PPE & Support supplies per day, internal: $9.00

ABSL2 PPE & Support supplies per day, commercial: $14.58

ABSL3 PPE & Support supplies per day, internal: $28.00

ABSL3 PPE & Support supplies per day, commercial: $45.36

*Fee structure to recover costs of PPE and other supplies that are not included in the per diem price structure.

Per Diem Cage Charges:

Mice (4 per cage):

ABSL2 per diem, internal: $0.88 cage/day

ABSL3 per diem, internal: $0.98 cage/day

ABSL2/ABSL3 per diem, commercial: $2.43 cage/day

Rats (2 per cage):

ABSL2/ABSL3 per diem, internal: $2.30 cage/day


Hamster (1-2 per cage):



Guinea Pig (1 per cage):



Cotton Rat (1 per cage):



Ferret (2 per cage):



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Common Service Procedures (full-service)**:

Organ collection, internal: $0.25 per tissue

Organ collection, commercial: $0.41 per tissue

Histopathology/IHC: Please inquire for a quote

Hematology, internal (1-49 samples): $25.00

Hematology, commercial (1-49 samples): $40.50

Clinical chemistry, internal: $15.00

Clinical chemistry, Commercial: $24.30

Aerosol Infection (BANG): Please inquire for a quote

Dose (IV bolus), internal: $1.50

Dose (IV bolus), commercial: $2.43

Dose (capsule), internal: $2.00

Dose (capsule), commercial: $3.24

Dose (gavage), internal $1.00

Dose (gavage), commercial: $1.62

Dose (IM inj.), internal $0.50

Dose (IM inj.), commercial: $0.81

Dose (SQ inj.), internal: $0.50

Dose (SQ inj.), commercial: $0.81

Dose (IP), internal: $0.50

Dose (IP), commercial: $0.81

Dose (retroorbital), internal: $1.50

Dose (retroorbital), commercial: $2.43

Vaccinate/infect (intranasal), internal: $0.75

Vaccinate/infect (intranasal), commercial: $1.22

Nasal Wash, internal: $1.50

Nasal Wash, commercial: $2.43

Nasal Swab, internal: $0.30

Nasal Swab, commercial: $0.49

Blood Col. VC, internal: $0.50

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Blood Col. VC, commercial: $0.81

Blood TV (blood drop), internal: $0.10

Blood TV (blood drop), commercial: $0.16

Blood retro orbital, internal: $0.75

Blood retro orbital, commercial: $1.22

Urine collection, internal: $0.25

Urine collection, commercial: $0.41

Removal w/o necropsy, internal: $0.10

Removal w/o necropsy, commercial: $0.16

Clinical obs/wts, internal: $0.25

Clinical obs/wts, commercial: $0.41

Temp w/transponder, internal: $0.50

Temp w/transponder, commercial: $0.81

Ear tagging, internal: $0.25

Ear tagging, commercial: $0.41

Consumables Please inquire for a quote

**Cost estimates for procedures are per mouse. Costs do not include not mice, ear tags or other consumables.

Additional Full Service Study-Specific Services (please inquire for a quote):

PK, PK-PD:

Single Dose Range

Multi Dose Range

Therapeutic Range

Delay of Treatment

Dosing Schedule & Route

Natural History of Infection

Vaccine Efficacy

Animal Services & Equipment ***:

Anesthesia machine no charge

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Clinical Chemistry:

Operator assisted, internal: $22.70/run

Operator assisted, commercial: $45.39/run

Full service, internal: Please inquire for a quote

Full service, commercial: Please inquire for a quote

Hematology:





IVIS Spectrum Bio-Imager:

Unassisted, internal: $100.00/run

Unassisted, commercial: $162.00/run





BANG (aerosol infection device):

Setup charge, internal: $ 50.00

Setup charge, commercial: $ 81.00

Decon charge, internal $ 50.00

Decon charge, commercial $ 81.00

Full service, internal Please inquire for a quote

Full service, commercial Please inquire for a quote

***Cost estimates for procedures for running instrumentation. Cost does not include mice or consumables.

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Pathogen & Small Molecule Discovery Services & Equipment:

Molecular Equipment****:

****Cost estimates for running instrumentation. Costs do not include consumables.

QuantStudio 6 qPCR** or EnVision Microplate Reader:







Synergy 2 Microplate Reader:







DeltaVision fluorescent microscope:

Unassisted, internal: $10.00/hr.

Unassisted, commercial: $16.20/hr.

Operator assisted, internal: $17.00/hr.

Operator assisted, commercial: $27.56/hr.



FACSAria II cell sorter:

Unassisted, internal: $52.00/hr.

Operator assisted, internal: $80.06/hr.

Full service, internal: $108.12/hr.

Full service, commercial: $175.15/hr.

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Luminex FX-200:

Direct Use per hour, internal $10.00/run

Assisted Use per hour, internal: $38.00/run



MagPix:





Illumina MiSeq System:

Operator assisted, internal: $105/run


MultiFlo FX:





Janus high-throughput robot:





Full Service Offerings:

Molecular Services (please inquire for a quote):

Assay Development

cDNA Synthesis

RT-qPCR 384 Plate

RT-qPCR 96 Well

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Cell to CT

96 well real-time PCR

386 well real-time PCR

Small molecule screening

MiSeq next generation sequencing library preparation

Immunology Services:

ELISA, Full Service per sample, internal: $13.00

ELISA, Full Service per sample, commercial: $21.06

Please inquire for a quote:

FACS Phenotyping, Full Service per hour, with assistance

FACS Sorting (Full Service Only)

FACS quantitative analysis, Full service per hour.

Luminex FX-200 Cytokine Assay, Full Service per run

MagPix Protein Assays, Full Service per run

MagPix Quantigene Assays, Full Service per run

Virology Services*****:

Virus Isolation, Full Service, per sample, internal: $217.00

Virus Isolation, Full Service, per sample, commercial: $351.54

Virus Plaque Assay, Full Service, per sample, internal $16.00

Virus Plaque Assay, Full Service, per sample, commercial $25.92

Viral TCID CPE Assay, Full Service, per 96 well plate, internal: $66.00

Viral TCID CPE Assay, Full Service, per 96 well plate, commercial: $106.92

Viral TCID HI Assay, Full Service, per 96 well plate, internal: $17.00

Viral TCID HI Assay, Full Service, per 96 well plate, commercial: $27.54

ELISA, Full Service per sample, internal: $13.00

ELISA, Full Service per sample, commercial: $21.06

Viral Neutralization Test, Full Service, per sample, internal: $17.00

Viral Neutralization Test, Full Service, per sample, commercial: $27.54

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Labor for all Full Service offerings, per hour, internal: $25.00

Labor Full Service offerings, per hour, commercial: $40.50

*****Labor Costs are not included.

Other Services:

Room Usage fee******:

BSL-2 shared, internal: No charge if in common area

BSL-2 shared, commercial: $50.00/day

BSL-2 exclusive use rate, internal: $28.00/day

BSL-3 shared, internal: $9.00/day

BSL-3 shared, commercial: $100.00/day

BSL-3 exclusive use rate, internal: $28.00/day

Pathogen Storage (long term): $3.00/day

******Fee structure to recover costs of PPE and other lab support supplies.

Biosafety Cabinet Certification*******:

Certification, per service, internal $100.00

Certification, per service, commercial: $162.00

Decontamination prior to filter

replacement or motor repairs, internal: $300.00

Decontamination prior to filter or

motor replacement repairs, commercial $486.00

BSC repair internal: per hr. per person $35.00/hr.

BSC repair commercial: per hr. per person* $56.70/hr.

BSC repair – No Show Fee $25.00

*******Note: Some repairs require two people.

Consulting Services, Internal & Commercial (please inquire for a quote):

Virology, Animal Study Design, Assay Development, Immunological Assay

High throughput screening (HTS) Full service

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SOP Development Full Service

Supplies:

Supplies ordered by RBL for use by investigators are provided at cost plus shipping.

In addition to these fee-for-service options, the RBL staff educate and train researchers to properly access and to employ the RBL facilities and to follow SOPs required to safely work with infectious and select agents. The following services are also provided at no charge:

A) Consultation with investigators and their staff on proposed experimental design during the planning phase

B) Active participation in internal seminars (Hot Topics series) and sponsorship of seminars related to infectious disease and select agents

C) Boilerplate language for facilities and resources for grant applications

D) Letters of support, including estimated costs of core usage for grant submissions

E) Assistance with completing IACUC Protocols and IBC Registration

IV: GRANTS THAT SUPPORTED THE CORE, FY18 • Jones, Byron

o NIH ES022614, Neural Toxicity of Paraquat is Related to Iron Regulation in the Midbrain

• Kumar, Santosh o NIH AA022063, Role of Cytochrome P450 in Alcohol-Mediated Effects on

Antiretroviral and HIV-1 • Kurosu, Michio

o NIH AI119796, Expansion of Spectrum of Activity of Pleuromutulin for MDR Gram-Negative Bacteria

• Kurosu, Michio o Cal Tech Subcontract to NIH GM114611, Mechanistic details of key

integral-membrane enzymes for antimicrobial discovery • Meibohm, Bernd

o St Jude Subcontract to NIH AI111449, Development of Aminospectinomycins for Biodefense

• Peters, Brian o LSUHSC Subcontract to NIH AI116025, Host and microbial factors

promoting synergistic mortality during polymicrobial intra-abdominal infections with Candida albicans and Staphylococcus aureus

• Peters, Brian o NIH AI110541, A Novel Role for the Inflammasome in the

Immunopathogenesis of Candida Vaginitis

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• Palmer, Glen o NIH AI099080, Molecular and Chemical Validation of the Vacuole as a

New Antifungal Target • Smith, Amber

o NIH AI100946, Bacterial Virulence Factors • Smith, Amber

o NIH AI025324, Quantifying and Validating Immune Response Dynamics for Influenza and Viral-Bacterial Pneumonias

• Tigyi, Gabor o NIH AI107331, IND Enabling Preclinical Development of a New

Radiomitigator

V. BUSINESS DEVELOPMENT A. Market Assessment

During FY18, RBL services were provided to 12 total UTHSC investigators from 7 departments and 2 university colleges (COM and COP). The RBL is defined as an institutional core based on its service to multiple Colleges and Departments within UTHSC. As the new Director, Dr. Jonsson will help recruit new investigators whose research programs will require RBL services, and she will work to build service units that can collaborate with investigators from academics or industry in the submission of new grants, contracts or fee for services from outside of UTHSC. Once Dr. Jonsson has the revised web site completed, new marketing materials, and newly recruited staff in place who are trained to execute work in new services currently in development, she will launch marketing or advertising of the services that we can provide to expand the customer base. The potential regional customers include the University of Memphis, Le Bonheur Hospital, St. Jude Children’s Research Hospital and other commercial and academic partners in the Memphis metropolitan area. A new customer this year that we are working with is the Shelby County Vector Control. Government customers may be acquired via several different mechanisms. Likely government clients include the Department of Defense, the Navy, the Defense Threat Reduction Agency, MCDC, BARDA, the Federal Bureau of Investigations, the National Advisory Council (NAC), the Centers for Disease Control and Prevention (CDC) and the United States Department of Agriculture (USDA). Funding mechanisms offered by government agencies include contracts and grants of various types, such as IDIQ (Indefinite Delivery, Indefinite Quantity) and OTA (Other Transactional Authority) contracts. Within these opportunities, we will primarily seek to secure contracts that use our RBL facilities for pathogen discovery, pathogen diagnostics or animal model development. Additional customers may include inter-institutional collaborators (“Friends” in the UT System, such as Dr. Klaus Schughart) and short-term academic PI visitors to our campus. A PI may wish to send to the RBL, a student and/or themselves to execute a research project. The RBL will develop approaches to facilitate short-

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term visits to train scientists in new technologies or to use our specialized service units within the RBL Core. The PI may also wish to have a person trained at our RBL to facilitate execution of their experiments since most research is highly technical and requires a great deal of background and expertise in the pathogen of interest. A PI may wish to send to the RBL, a student and/or themselves to execute a research project or provide direct oversight. Large and small commercial entities continue to move toward out-sourcing capability that is expensive to maintain when of limited use or specialized to the overall mandate of the company. For example, a company may have an adjuvant and desire testing against BSL-2 and BSL-3 agents. The company may have BSL-2, but, it would not be profitable for the company to devote resources to building BSL-3 capacity. Similarly, for drug discovery, many small biotech companies have one lead compound, and to in order to build their patent portfolio, they will seek services to define the use of their compound against an array of pathogens. Opportunities may exist to partner with biotechnology to create a larger effort that neither could manage alone. For example, most companies would rather the drug discovery aspects be brought to preclinical or phase 1 prior to licensing. Companies may wish to partner as a right of first refusal for inventions discovered at the RBL. State of Tennessee agencies, such as hospitals, public health laboratories may wish to use services that can be provided by the RBL. These include but are not limited to the growth of viruses and bacteria for identification (e.g. via sequencing, SNPs) in general population surveys, to develop new methods for isolating organisms for detection, or to provide a testing ground for new concepts in multiplexing pathogen detection arrays. In general, the RBL will seek to provide state-of-the-art technologies to facilitate public health in our State. The RBL is capable of providing support for environmental surveys for human and animal outbreaks of pathogens, storage and tracking of select agents to provide the State with the ability to create panels for disease diagnosis and detection. This is particularly important given that these labs are typically not allowed to store specimens after they are identified, if they are select agents. Other not-for-profit entities, such as One World Health, have demonstrated the ability to provide a niche in drug development for treatments for tropical diseases. Partnerships with these organizations will be the most valuable to the University and will also be the most synergistic. These types of collaborative efforts would likely seek support for a common mission through fundraising. For example, the availability of adjuvants approved by the FDA is a current unmet need. UTHSC RBL could partner with One World Health to provide adjuvants which they would bring through the development pipeline

B. Competitive Analysis

There are 2 National and 11 Regional Biocontainment facilities in the US. Because the RBL grants from the National Institute of Allergy and Infectious

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Diseases (NIAID) were used to build the facilities but did not supply any operational budget for the RBLs, it has become necessary for the UTHSC RBL, and all other RBLs, to identify several approaches for generating revenue to offset the considerable operational costs to staff and to maintain these facilities. The approaches include attracting federally-funded academic researchers, or private sector researchers, to perform their work in the RBL facilities, as well as contract, fee-for-service research conducted by RBL staff. There are a number of issues that have made it difficult to attract research activities to the UTHSC RBL:

(1) Each of the RBLs are under the same financial pressures, and they can be in direct competition with each other for attracting research (e.g., the University of Alabama, Birmingham and the University of Louisville are direct competitors of the UTHSC RBL). (2) There are numerous other containment facilities around the country that are also competing for users/projects. Many of these facilities are located at academic institutions, and others are either commercial (e.g. Battelle) or are government-funded (e.g. Lawrence Livermore National Lab, and United States Army Medical Research Institute of Infectious Diseases, USAMRIID) operations. It is especially difficult to compete with the big commercial and governmental laboratories because they are very well-staffed with research teams with dedicated expertise and they have a wide array of core research facilities. (3) Since the RBL was constructed, there has been a near total absence of recruiting researchers whose research programs require BSL-3/ABSL-3 containment laboratory space, and the University has failed to retain several funded researchers whose work required BSL-3/ABSL-3 containment. Therefore, it is to our advantage to understand what other RBLs and BSL3 labs have to offer and to focus on our unique strengths or areas that are not widely available. For example, host-pathogen systems biology (i.e., ISHPS) is one of the areas that focuses on UTHSC’s unique strengths. Overall, external, academic (outside university) customers will typically be principal investigators (PI) who have been awarded a government grant or contract who do not have BSL-3, ABSL-3 and/or access to the specialized equipment managed locally at their institution.

C. Marketing Plans to Obtain New Business For each of the “Units” areas of service at the UTHSC RBL, we need to understand the value proposition to win “business”. Each of the units within RBL should, and will be, described with a snapshot of current capability, gaps and value proposition that explains: -how our core capability and capacity solve customers' problems or improves their situation (relevancy) -explains how our core capability and capacity delivers specific benefits (quantified value)

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-tells the ideal customer why they should work with us and not with the competition (unique differentiation) Overall value proposition Relevancy: The RBL is the only facility available to UTHSC or external users in the Memphis area on a collaborative or fee-for-service basis that has the appropriate engineering controls, facilities and resources for BSL3/ABSL3 research. Agents that may cause serious or lethal disease through the inhalation route of exposure will benefit from the type of engineering controls, resources and facilities that the UTHSC RBL offers. As an academic, not for profit entity, our services cannot make a profit. This provides commercial partners with a low-cost alternative to a corporate research organization or CRO. Unique differentiation: The availability of unique in vitro assays and in vivo small animal models will deliver added value for customers. The RBL is developing a new full-service menu to support animal studies, from pre-experiment design, to animal procurement, to a wide array of animal services, and after-life endpoints. The RBL will stand up a wide inventory of techniques in virology, bacteriology and immunology, with a focus on emerging infectious diseases and select agents, which will be an important discriminator with our competition. Small Animal Model-Pathogen Evaluation Unit Government and commercial clients will seek service partners that can provide a wide arrange of services. We will position ourselves to support clients in efficacy testing studies that provide them with critical capability that sets their studies apart and helps them evaluate their product fast. For example, we will help customers evaluate small molecules prior to embarking onto an efficacy study, so that they have the best information available on compound formulation, route of administration and animal model. Pathogen and Molecular Discovery Unit Relevancy: The high throughput robotic instrumentation currently located in the BSL3 is not widely available nation-wide. Our goal will be to have highly trained staff that provide the highest quality of service in the shortest time for the lowest price. The RBL will provide services to improve assays to be ready for high throughput screening (HTS), offering highly qualified staff, reproducible results and a documented track record in this area advertised in new marketing materials. To support this Unit, we offer the Perkin-Elmer Janus HTS robots, an Envision multi-modal plate reader (Synergy 2), chemical libraries procured through partnerships and PI-based material transfer agreements and siRNA libraries.

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Based on current vivarium staffing, the UTHSC could provide: 1 full service animal study every 2-3 months with downstream in vitro analyses which can take up to 8 weeks- Target: 6 studies per year The brand strategy is the long-term plan for the development of the “RBL” as a successful brand with the over goal of being recognized as a collaborative unit and a center of excellence for conducting studies that lead to greater biological understanding of pathogenic organisms and approaches for evaluation of antivirals, therapeutics and vaccines. This is the major purpose of our brand.

VI. Budget FY18 Actual Budget (July 1, 2017 - June 30, 2018)

FY2018 DEBITS CREDITS Salaries $704,946 Supplies $197,722 Service Contracts $119,425 Equipment (> $5,000) $91,029 Other Expenses* $57,171 TOTAL EXPENSES $1,170,295 FY 18 Internal Core Recoveries FY18 External Core Recoveries FY18 State Appropriation**

$130,550 $130

$737,969 TOTAL CREDITS $868,649 Income / (Subsidy)** ($301,646)

*Other expenses consist of the following: Travel, Media/Communications, Maintenance/Repairs, Memberships, Copier Rental and Registration Fees.

Subsidy, prior to the State appropriation: 89% ($1,039,615).

Subsidy, after the State appropriation: 25.7% ($301,646).

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Molecular Resource Center of Excellence (MRC)

Molecular Resource Center of Excellence (MRC) Institutional Research Core Facility Analysis Report- FY18 Written by William Taylor, PhD; and Tiffany N. Seagroves, PhD

1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The MRC core designation as an institutional core is appropriate since it served 91 total users (79 internal and 12 external) across 19 departments and four Colleges and 7 external institutions (UTK and 5 other academic centers and 1 commercial user).

2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. In FY18, this core processed >15,000 total units of service on behalf of 79 unique internal users across 19 departments and three Colleges (COM, COP, CON and COD). The MRC also served 12 unique external users from six external academic centers and one commercial entity, including the Memphis VA, Rhodes College, University of Nebraska, and Genome Explorations. The two Departments with the largest number of unique users were the Department of Pediatrics (COM) and Department of Anatomy & Neurobiology (COM), with 12 and eight unique users, respectively. The top five users, based on the percentage of collected revenues per PI versus total core revenues ($264,401), accounted for 41.89% of total revenues. These investigators were: 1) Robert Williams (GGI, 15.56%), 2) Steven Youngentob (Anatomy & Neurobiology, COM, 13.18%) 3) P. David Rogers (Clinical Pharmacy, COP, 6.08%), 4) Subhash Chauhan (Pharmaceutical Sciences, COP, 3.6%) and 5) Ivan Gerling (Medicine, COM, 3.47%). The remaining internal core users accounted for the other 58.11% of revenues.

3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. There were 79 unique internal users who were served across 19 departments and four Colleges at UTHSC.

4. Can the services for the core be outsourced more economically? No. Moreover, few academic cores continue to offer Affymetrix microarray services, which are still processed in high-volume at the MRC.

5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led to 215 PubMed-indexed publications. A total of 51 grants and contracts were supported by the MRC in FY18. In addition, Dr. Taylor provided expert consultation for over 70 proposed projects. Dr. Taylor and the MRC staff also provided hands-on training in molecular technologies to >20 new core users, primarily new students, residents and/or postdocs. 6. Is the core currently self-sufficient, or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution and by the THEC appropriation. FY18 ended with a net income of $31,338.

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Accomplishments this past year: • Optimized workflow for use of the Hamilton Starlet Liquid Handling Robot (subsidized by the VC for Research in FY17) for next-generation sequencing (NGS) library preparation protocols. • The MRC core supported numerous publications, abstract presentations and extramural and intramural awards, as well as sponsored five special technology seminars that were well-attended. • The MRC also continued its mission of education providing hands-on training to laboratory personnel. • The MRC Director conducted lab tours and information sessions for 14 prospective faculty members. • The MRC Director provided >70 experimental design consultations for clients. Financial Overview - FY18:

TOTALS FY17 FY18 Revenues 408,427 264,401 State Appropriation 602,887 620,121 Revenues & Appropriation 1,011,314 884,522 Expenses (1,033,779) (853,184) Income (Subsidy) (22,465) 31,338 Equipment* 100,651 0 Net Income (Subsidy) (123,116) 31,338 Subsidy, %* 10.8%* --

*All equipment in FY17 was subsidized by the VC for Research startup fund.

7. Suggested outcomes: It is recommended that the MRC continue as an institutional core.

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Molecular Resource Center of Excellence (MRC) Core Summary of Institutional Core Activities for FY18 Written by William Taylor, PhD; Lorne Rose, BS; Cotina Williams; Natalie Smith, MS; and Tiffany N. Seagroves, PhD I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018) Full-length published articles (UTHSC faculty investigators are indicated in bold font)

1. Computational analysis of envelope glycoproteins from diverse geographical isolates of bovine leukemia virus identifies highly conserved peptide motifs. Pluta A, Albritton LM, Rola-Łuszczak M, Kuźmak J. Retrovirology. 2018 Jan 8;15(1):2. doi: 10.1186/s12977-017-0383-0. PMID:29310678

2. Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy. Wang L, Chandaka GK, Foehring RC, Callaway JC, Armstrong WE. J Neurophysiol. 2018 May 1;119(5):1745-1752. doi: 10.1152/jn.00608.2017. PMID:29537926

3. Phosphatidylinositol 4,5-bisphosphate (PIP2) modulates afterhyperpolarizations in oxytocin neurons of the supraoptic nucleus. Kirchner MK, Foehring RC, Wang L, Chandaka GK, Callaway JC, Armstrong WE. J Physiol. 2017 Jul 15;595(14):4927-4946. doi: 10.1113/JP274219. PMID:28383826

4. Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece. Avgeris S, Fostira F, Vagena A, Ninios Y, Delimitsou A, Vodicka R, Vrtel R, Youroukos S, Stravopodis DJ, Vlassi M, Astrinidis A, Yannoukakos D, Voutsinas GE. Sci Rep. 2017 Dec 1;7(1):16697. doi: 10.1038/s41598-017-16988-w. PMID:29196670

5. Generation, clearance, toxicity and monitoring possibilities of unaccounted uremic toxins for improved dialysis prescriptions. Atherton JG, Hains DS, Bissler JJ, Pendley BD, Lindner E. Am J Physiol Renal Physiol. 2018 Mar 14. doi: 10.1152/ajprenal.00106.2017. PMID:29537310

6. The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma. Bissler JJ, Franz DN, Frost MD, Belousova E, Bebin EM, Sparagana S, Berkowitz N, Ridolfi A, Kingswood JC. Pediatr Nephrol. 2018 Jan;33(1):101-109. doi: 10.1007/s00467-017-3806-1. Epub 2017 Oct 9. PMID:28993887

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7. Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study. Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Belousova E, Frost MD, Sauter M, Brakemeier S, de Vries PJ, Berkowitz N, Voi M, Peyrard S, Budde K. PLoS One. 2017 Aug 9;12(8):e0180939. doi: 10.1371/journal.pone.0180939. eCollection 2017. PMID:28792952

8. Anterior Skull Base Reconstruction: Does Fat Preparation Matter? Wood J, Densky J, Boughter J, Sebelik M, Shires C. J Neurol Surg Rep. 2018 Apr;79(2):e31-e35. doi: 10.1055/s-0038-1645886. PMID:29761066

9. Overlapping Representation of Primary Tastes in a Defined Region of the Gustatory Cortex. Fletcher ML, Ogg MC, Lu L, Ogg RJ, Boughter JD Jr. J Neurosci. 2017 Aug 9;37(32):7595-7605. doi: 10.1523/JNEUROSCI.0649-17.2017. PMID:28674169

10. Comparing Cancellous Bone Volume of the Manubrium to Iliac Crest in Fresh Cadavers. Smith A, Kortebein S, Eid A, Boughter J, Cary N, Brooks J, Sebelik M. Otolaryngol Head Neck Surg. 2017 Jul;157(1):36-41. doi: 10.1177/0194599817692961. PMID:28669310

11. Genetic control of oromotor phenotypes: A survey of licking and ingestive behaviors in highly diverse strains of mice. St John SJ, Lu L, Williams RW, Saputra J, Boughter JD Jr. Physiol Behav. 2017 Aug 1;177:34-43. doi: 10.1016/j.physbeh.2017.04.007. PMID:28411104

12. Classification system for lateral pharyngotomy: systematic study of anatomic exposure in a human cadaver model. Shires C, Smith A, Lee J, Boughter J, Sebelik M. Surg Radiol Anat. 2017 Sep;39(9):975-979. doi: 10.1007/s00276-017-1827-x. PMID:28243697

13. Calcium- and voltage-gated BK channels in vascular smooth muscle. Dopico AM, Bukiya AN, Jaggar JH. Pflugers Arch. 2018 May 11. doi: 10.1007/s00424-018-2151-y. Review. PMID:29748711

14. Fetal Cerebral Circulation as Target of Maternal Alcohol Consumption. Bukiya AN, Dopico AM. Alcohol Clin Exp Res. 2018 Jun;42(6):1006-1018. doi: 10.1111/acer.13755. Review. PMID:29672868

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15. Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. Dopico AM, Bukiya AN, Bettinger JC. Handb Exp Pharmacol. 2017 Dec 5. doi: 10.1007/164_2017_78. PMID:29204711

16. The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy. Tobiasz AM, Duncan JR, Bursac Z, Sullivan RD, Tate DL, Dopico AM, Bukiya AN, Mari G. Reprod Sci. 2018 Jul;25(7):1116-1123. doi: 10.1177/1933719117734317. PMID:28982294

17. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle. Simakova MN, Bisen S, Dopico AM, Bukiya AN. Biochem Pharmacol. 2017 Dec 1;145:81-93. doi: 10.1016/j.bcp.2017.08.022. PMID:28865873

18. Regulation of Ca2+-Sensitive K+ Channels by Cholesterol and Bile Acids via Distinct Channel Subunits and Sites. Dopico AM, Bukiya AN. Curr Top Membr. 2017;80:53-93. doi: 10.1016/bs.ctm.2017.07.001. Review. PMID:28863822

19. Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy. Almabadi HM, Nagesh PKB, Sahay P, Bhandari S, Eckstein EC, Jaggi M, Chauhan SC, Yallappu MM, Pradhan P. J Biophotonics. 2018 Jun 5:e201800056. doi: 10.1002/jbio.201800056. PMID:29869394

20. Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposes. Tripathi MK, Doxtater K, Keramatnia F, Zacheaus C, Yallapu MM, Jaggi M, Chauhan SC. Drug Discov Today. 2018 Apr 23. pii: S1359-6446(18)30071-0. doi: 10.1016/j.drudis.2018.04.010. Review. PMID:29698834

21. Antibody-Drug Conjugates for Cancer Therapy: Chemistry to Clinical Implications. Dan N, Setua S, Kashyap VK, Khan S, Jaggi M, Yallapu MM, Chauhan SC. Pharmaceuticals (Basel). 2018 Apr 9;11(2). pii: E32. doi: 10.3390/ph11020032. Review. PMID:29642542

22. Tannic Acid Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Prostate Cancer. Nagesh PKB, Hatami E, Chowdhury P, Kashyap VK, Khan S, Hafeez BB, Chauhan SC, Jaggi M, Yallapu MM. Cancers (Basel). 2018 Mar 7;10(3). pii: E68. doi: 10.3390/cancers10030068. PMID:29518944

23. Targeting IκappaB kinases for cancer therapy. Awasthee N, Rai V, Chava S, Nallasamy P, Kunnumakkara AB, Bishayee A, Chauhan SC, Challagundla KB, Gupta SC. Semin Cancer Biol. 2018 Feb 24. pii: S1044-579X(17)30046-9. doi: 10.1016/j.semcancer.2018.02.007. Review. PMID:29486318

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24. MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer.

Kumari S, Khan S, Gupta SC, Kashyap VK, Yallapu MM, Chauhan SC, Jaggi M. Oncogenesis. 2018 Feb 22;7(2):19. doi: 10.1038/s41389-018-0031-0. PMID:29467405

25. Protein kinase D1 regulates subcellular localisation and metastatic function of metastasis-associated protein 1. Ganju A, Chauhan SC, Hafeez BB, Doxtater K, Tripathi MK, Zafar N, Yallapu MM, Kumar R, Jaggi M. Br J Cancer. 2018 Feb 20;118(4):587-599. doi: 10.1038/bjc.2017.431. PMID:29465084

26. Clinical significance of MUC13 in pancreatic ductal adenocarcinoma. Khan S, Zafar N, Khan SS, Setua S, Behrman SW, Stiles ZE, Yallapu MM, Sahay P, Ghimire H, Ise T, Nagata S, Wang L, Wan JY, Pradhan P, Jaggi M, Chauhan SC. HPB (Oxford). 2018 Jun;20(6):563-572. doi: 10.1016/j.hpb.2017.12.003. PMID:29352660

27. Quantification of photonic localization properties of targeted nuclear mass density variations: Application in cancer-stage detection. Sahay P, Ganju A, Almabadi HM, Ghimire HM, Yallapu MM, Skalli O, Jaggi M, Chauhan SC, Pradhan P. J Biophotonics. 2018 May;11(5):e201700257. doi: 10.1002/jbio.201700257. PMID:29222925

28. Knockdown of survivin results in inhibition of epithelial to mesenchymal transition in retinal pigment epithelial cells by attenuating the TGFβ pathway. Zhang P, Zhao G, Ji L, Yin J, Lu L, Li W, Zhou G, Chaum E, Yue J. Biochem Biophys Res Commun. 2018 Apr 6;498(3):573-578. doi: 10.1016/j.bbrc.2018.03.021. PMID:29522718

29. Recent Advances in Retinal Stem Cell Therapy. Bhattacharya S, Gangaraju R, Chaum E. Curr Mol Biol Rep. 2017 Sep;3(3):172-182. doi: 10.1007/s40610-017-0069-3. PMID:29152454

30. Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment Epithelium. Bhattacharya S, Yin J, Winborn CS, Zhang Q, Yue J, Chaum E. Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):2366-2387. doi: 10.1167/iovs.16-21162. PMID:28437526

31. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells. Huo W, Zhao G, Yin J, Ouyang X, Wang Y, Yang C, Wang B, Dong P, Wang Z, Watari H, Chaum E, Pfeffer LM, Yue J. J Cancer. 2017 Jan 1;8(1):57-64. doi: 10.7150/jca.16723. eCollection 2017. PMID:28123598

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32. Novel Small Molecule JP-153 Targets the Src-FAK-Paxillin Signaling Complex to Inhibit VEGF-Induced Retinal Angiogenesis. Toutounchian JJ, Pagadala J, Miller DD, Baudry J, Park F, Chaum E, Yates CR. Mol Pharmacol. 2017 Jan;91(1):1-13. PMID:27913654

33. The rice terpene synthase gene OsTPS19 functions as an (S)-limonene synthase in planta, and its overexpression leads to enhanced resistance to the blast fungus Magnaporthe oryzae. Chen X, Chen H, Yuan JS, Köllner TG, Chen Y, Guo Y, Zhuang X, Chen X, Zhang YJ, Fu J, Nebenführ A, Guo Z, Chen F. Plant Biotechnol J. 2018 Mar 6. doi: 10.1111/pbi.12914. [PMID:29509987

34. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression. Raghavan NS, Chen H, Schipma M, Luo W, Chung S, Wang L, Redei EE. Front Endocrinol (Lausanne). 2018 Jan 22;8:373. doi: 10.3389/fendo.2017.00373. eCollection 2017. PMID:29403433

35. Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis. Xiao Z, Baudry J, Cao L, Huang J, Chen H, Yates CR, Li W, Dong B, Waters CM, Smith JC, Quarles LD. J Clin Invest. 2018 Jan 2;128(1):157-174. doi: 10.1172/JCI93725. Epub 2017 Nov 27. PMID:29202470

36. 1α,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structure and Route of Chemical Synthesis. Lin Z, Chen H, Belorusova AY, Bollinger JC, Tang EKY, Janjetovic Z, Kim TK, Wu Z, Miller DD, Slominski AT, Postlethwaite AE, Tuckey RC, Rochel N, Li W. Sci Rep. 2017 Aug 31;7(1):10193. doi: 10.1038/s41598-017-10917-7. PMID:28860545

37. Social learning promotes nicotine self-administration by facilitating the extinction of conditioned aversion in isogenic strains of rats. Han W, Wang T, Chen H. Sci Rep. 2017 Aug 14;7(1):8052. doi: 10.1038/s41598-017-08291-5. PMID:28808247

38. Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy. Chen H, Lin Z, Arnst KE, Miller DD, Li W. Molecules. 2017 Aug 1;22(8). pii: E1281. doi:10.3390/molecules22081281. Review. PMID:28763044

39. Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons. Kridsada K, Niu J, Haldipur P, Wang Z, Ding L, Li JJ, Lindgren AG, Herrera E, Thomas GM, Chizhikov VV, Millen KJ, Luo W. Cell Rep. 2018 Jun 5;23(10):2928-2941. doi: 10.1016/j.celrep.2018.05.025. PMID:29874580

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40. A Phosphatidylserine Source of Docosahexanoic Acid Improves Neurodevelopment and Survival of Preterm Pigs. Buddington RK, Chizhikov VV, Iskusnykh IY, Sable HJ, Sable JJ, Holloway ZR, Blumenfeld Katzir T, van der Merwe M, Yakimkova T, Buddington KK, Lifshitz Y, Tessler S, Gilbert A. Nutrients. 2018 May 18;10(5). pii: E637. doi: 10.3390/nu10050637. PMID:29783637

41. Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia. Iskusnykh IY, Buddington RK, Chizhikov VV. Exp Neurol. 2018 Aug;306:209-221. doi: 10.1016/j.expneurol.2018.05.015. Epub 2018 May 14. PMID:29772246

42. Wilhelm His' lasting insights into hindbrain and cranial ganglia development and evolution. Glover JC, Elliott KL, Erives A, Chizhikov VV, Fritzsch B. Dev Biol. 2018 Feb 12. pii: S0012-1606(17)30584-5. doi: 10.1016/j.ydbio.2018.02.001. [Epub ahead of print] Review. PMID:29447907

43. Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress. Bhatti FUR, Kim SJ, Yi AK, Hasty KA, Cho H. Cell Tissue Res. 2018 Jun 27. doi: 10.1007/s00441-018-2857-3. [Epub ahead of print] PMID:29951700

44. Noninvasive visualization of early osteoarthritic cartilage using targeted nanosomes in a destabilization of the medial meniscus mouse model. Cho H, Kim BJ, Park SH, Hasty KA, Min BH. Int J Nanomedicine. 2018 Mar 1;13:1215-1224. doi: 10.2147/IJN.S149375. eCollection 2018. PMID:29535518

45. A 16.7 kb deletion in Sipa1l3 is associated with juvenile cataract in mice. Walker LR, Tosky ER, Sutton KM, Griess R, Abebe MD, Barnes SY, Cunnigham T, Kachman SD, Nielsen MK, Ciobanu DC. Mamm Genome. 2017 Dec;28(11-12):515-519. doi: 10.1007/s00335-017-9720-9. PMID:28951961

46. Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6). Azumaya CM, Sierra-Valdez F, Cordero-Morales JF, Nakagawa T. J Biol Chem. 2018 Jun 29;293(26):10381-10391. doi:10.1074/jbc.RA118.003183. PMID:29752403

47. How lipids contribute to ion channel function, a fat perspective on direct and indirect interactions. Cordero-Morales JF, Vásquez V. Curr Opin Struct Biol. 2018 Mar 28;51:92-98. doi: 10.1016/j.sbi.2018.03.015. Review. PMID:29602157

48. Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling. Caires R, Sierra-Valdez FJ, Millet JRM, Herwig JD, Roan E,

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Vásquez V, Cordero-Morales JF. Cell Rep. 2017 Oct 3;21(1):246-258. doi: 10.1016/j.celrep.2017.09.029. PMID:28978477

49. Expression and Purification of the Pain Receptor TRPV1 for Spectroscopic Analysis. Velisetty P, Stein RA, Sierra-Valdez FJ, Vásquez V, Cordero-Morales JF. Sci Rep. 2017 Aug 29;7(1):9861. doi: 10.1038/s41598-017-10426-7. PMID:28852163

50. New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis. Kimura D, Saravia J, Jaligama S, McNamara I, Vu LD, Sullivan RD, Mancarella S, You D, Cormier SA. Am J Physiol Heart Circ Physiol. 2018 Jun 15. doi: 10.1152/ajpheart.00627.2017. PMID:29906223

51. Radical containing combustion derived particulate matter enhance pulmonary Th17 inflammation via the aryl hydrocarbon receptor. Jaligama S, Patel VS, Wang P, Sallam A, Harding J, Kelley M, Mancuso SR, Dugas TR, Cormier SA. Part Fibre Toxicol. 2018 May 3;15(1):20. doi: 10.1186/s12989-018-0255-3. PMID:29724254

52. NKG2D is Required for Regulation of Lung Pathology and Dendritic Cell Function Following RSV Infection. Liu H, Osterburg AR, Flury J, Huang S, McCormack FX, Cormier SA, Borchers MT. J Infect Dis. 2018 Mar 15. doi: 10.1093/infdis/jiy151. PMID:29554301

53. A Scalable Field Study Protocol and Rationale for Passive Ambient Air Sampling: A Spatial Phytosampling for Leaf Data Collection. Oyana TJ, Lomnicki SM, Guo C, Cormier SA. Environ Sci Technol. 2017 Sep 19;51(18):10663-10673. doi: 10.1021/acs.est.7b03643. PMID:28805054

54. Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants. Brint ME, Hughes JM, Shah A, Miller CR, Harrison LG, Meals EA, Blanch J, Thompson CR, Cormier SA, DeVincenzo JP. Pediatr Res. 2017 Nov;82(5):872-880. doi: 10.1038/pr.2017.173. PMID:28723886

55. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy. Ponnusamy S, Sullivan RD, You D, Zafar N, He Yang C, Thiyagarajan T, Johnson DL, Barrett ML, Koehler NJ, Star M, Stephenson EJ, Bridges D, Cormier SA, Pfeffer LM, Narayanan R. Hum Mol Genet. 2017 Jul 1;26(13):2526-2540. doi: 10.1093/hmg/ddx150. PMID:28453658

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56. Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged with Respiratory Syncytial Virus: A Placebo-Controlled Study. Stevens M, Rusch S, DeVincenzo J, Kim YI, Harrison L, Meals EA, Boyers A, Fok-Seang J, Huntjens D, Lounis N, Mari N K, Remmerie B, Roymans D, Koul A, Verloes R. J Infect Dis. 2018 Apr 19. doi: 10.1093/infdis/jiy227. [Epub ahead of print] PMID:29684148

57. Do asymptomatic respiratory viral infections occur? Tomlinson RH, Harrison LG, Meals EA, DeVincenzo JP. J Clin Virol. 2018 May;102:93-94. doi: 10.1016/j.jcv.2018.03.002. Epub 2018 Mar 5. No abstract available. PMID:29529485

58. The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin. Kim YI, Pareek R, Murphy R, Harrison L, Farrell E, Cook R, DeVincenzo J. Influenza Other Respir Viruses. 2017 Nov;11(6):525-530. doi: 10.1111/irv.12503. Epub 2017 Oct 30. PMID:28990339

59. Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines. Kim L, Rha B, Abramson JS, Anderson LJ, Byington CL, Chen GL, DeVincenzo J, Edwards KM, Englund JA, Falsey AR, Griffin MR, Karron RA, Martin KG, Meissner HC, Munoz FM, Pavia AT, Piedra PA, Schaffner W, Simões EAF, Singleton R, Talbot HK, Walsh EE, Zucker JR, Gerber SI. Clin Infect Dis. 2017 Sep 15;65(6):1020-1025. doi: 10.1093/cid/cix432. PMID:28903503

60. Deep sequencing of RSV from an adult challenge study and from naturally infected infants reveals heterogeneous diversification dynamics. Lau JW, Kim YI, Murphy R, Newman R, Yang X, Zody M, DeVincenzo J, Grad YH. Virology. 2017 Oct;510:289-296. doi: 10.1016/j.virol.2017.07.017. PMID:28779686

61. SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans. Allen EK, Randolph AG, Bhangale T, Dogra P, Ohlson M, Oshansky CM, Zamora AE, Shannon JP, Finkelstein D, Dressen A, DeVincenzo J, Caniza M, Youngblood B, Rosenberger CM, Thomas PG. Nat Med. 2017 Aug;23(8):975-983. doi: 10.1038/nm.4370. PMID:28714988

62. Preclinical Characterization of PC786, an Inhaled Small-Molecule Respiratory Syncytial Virus L Protein Polymerase Inhibitor. Coates M, Brookes D, Kim YI, Allen H, Fordyce EAF, Meals EA, Colley T, Ciana CL, Parra GF, Sherbukhin V, Stockwell JA, Thomas JC, Hunt SF, Anderson-Dring L, Onions ST, Cass L, Murray PJ, Ito K, Strong P, DeVincenzo JP, Rapeport G. Antimicrob Agents Chemother. 2017 Aug 24;61(9). pii: e00737-17. doi: 10.1128/AAC.00737-17. Print 2017 Sep. PMID:28652242

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63. A human challenge model for respiratory syncytial virus kinetics, the

pharmacological effect of a novel fusion inhibitor, and the modelling of symptoms scores. Korell J, Green B, DeVincenzo J, Huntjens D. Eur J Pharm Sci. 2017 Nov 15;109S:S154-S160. doi: 10.1016/j.ejps.2017.05.070. PMID:28606804

64. Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes. Okeke E, Dokun AO. Exp Biol Med (Maywood). 2018 Jan;243(2):190-197. doi: 10.1177/1535370217743460. PMID:29199462

65. Modulation of miR29a improves impaired post-ischemic angiogenesis in hyperglycemia. Chen L, Okeke E, Ayalew D, Wang D, Shahid L, Dokun AO. Exp Biol Med (Maywood). 2017 Aug;242(14):1432-1443. doi: 10.1177/1535370217716424. PMID:28637396

66. BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy. McClung JM, McCord TJ, Ryan TE, Schmidt CA, Green TD, Southerland KW, Reinardy JL, Mueller SB, Venkatraman TN, Lascola CD, Keum S, Marchuk DA, Spangenburg EE, Dokun A, Annex BH, Kontos CD. Circulation. 2017 Jul 18;136(3):281-296. doi: 10.1161/CIRCULATIONAHA.116.024873. PMID:28442482

67. Role of Fibroblast Growth Factor-23 in Innate Immune Responses. Fitzpatrick EA, Han X, Xiao Z, Quarles LD. Front Endocrinol (Lausanne). 2018 Jun 12;9:320. Doi: 10.3389/fendo.2018.00320. eCollection 2018. Review. PMID:29946298

68. A Neonatal Murine Model of MRSA Pneumonia. Fitzpatrick EA, You D, Shrestha B, Siefker D, Patel VS, Yadav N, Jaligama S, Cormier SA. PLoS One. 2017 Jan 6;12(1):e0169273. doi: 10.1371/journal.pone.0169273. eCollection 2017. PMID:28060871

69. Olfactory bulb acetylcholine release dishabituates odor responses and reinstates odor investigation. Ogg MC, Ross JM, Bendahmane M, Fletcher ML. Nat Commun. 2018 May 14;9(1):1868. doi: 10.1038/s41467-018-04371-w. PMID:29760390

70. Learning-Dependent and -Independent Enhancement of Mitral/Tufted Cell Glomerular Odor Responses Following Olfactory Fear Conditioning in Awake Mice. Ross JM, Fletcher ML. J Neurosci. 2018 May 16;38(20):4623-4640. doi: 10.1523/JNEUROSCI.3559-17.2018. Epub 2018 Apr 18. PMID:29669746

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71. Commonly Used Oncology Drugs Decrease Antifungal Effectiveness against Candida and Aspergillus Species. Butts A, Reitler P, Ge W, Fortwendel JR, Palmer GE. Antimicrob Agents Chemother. 2018 Jun 26;62(7). pii: e00504-18. doi: 10.1128/AAC.00504-18. Print 2018 Jul. PMID:29712657

72. C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus. Al Abdallah Q, Martin-Vicente A, Souza ACO, Ge W, Fortwendel JR. Front Microbiol. 2018 Mar 26;9:562. doi: 10.3389/fmicb.2018.00562. eCollection 2018. PMID:29632525

73. A Simple and Universal System for Gene Manipulation in Aspergillus fumigatus: In Vitro-Assembled Cas9-Guide RNA Ribonucleoproteins Coupled with Microhomology Repair Templates. Al Abdallah Q, Ge W, Fortwendel JR. mSphere. 2017 Nov 22;2(6). pii: e00446-17. doi: 10.1128/mSphere.00446-17. eCollection 2017 Nov-Dec. PMID:29202040

74. Abnormal islet sphingolipid metabolism in type 1 diabetes. Holm LJ, Krogvold L, Hasselby JP, Kaur S, Claessens LA, Russell MA, Mathews CE, Hanssen KF, Morgan NG, Koeleman BPC, Roep BO, Gerling IC, Pociot F, Dahl-Jørgensen K, Buschard K. Diabetologia. 2018 Jul;61(7):1650-1661. doi: 10.1007/s00125-018-4614-2. PMID:29671030

75. Comparative quantitative proteomic analysis of disease stratified laser captured microdissected human islets identifies proteins and pathways potentially related to type 1 diabetes. Nyalwidhe JO, Grzesik WJ, Burch TC, Semeraro ML, Waseem T, Gerling IC, Mirmira RG, Morris MA, Nadler JL. PLoS One. 2017 Sep 6;12(9):e0183908. doi: 10.1371/journal.pone.0183908. eCollection 2017. PMID:28877242

76. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge. Elam MB, Majumdar G, Mozhui K, Gerling IC, Vera SR, Fish-Trotter H, Williams RW, Childress RD, Raghow R. PLoS One. 2017 Aug 3;12(8):e0181308. doi: 10.1371/journal.pone.0181308. eCollection 2017. PMID:28771594

77. Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy. Tripathi R, Sullivan R, Fan TM, Wang D, Sun Y, Reed GL, Gladysheva IP. PLoS One. 2017 Dec 14;12(12):e0189315. doi: 10.1371/journal.pone.0189315. eCollection 2017. PMID:29240788

78. What's New in Critical Illness and Injury Science? Case reports: The first step on a path toward cure. Gosain A. Int J Crit Illn Inj Sci. 2018 Apr-Jun;8(2):55-56. doi: 10.4103/2229-5151.234585. PMID:29963406

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79. A Roadmap for Aspiring Surgeon-Scientists in Today's Healthcare Environment. Goldstein AM, Blair AB, Keswani SG, Gosain A, Morowitz M, Kuo J, Levine M, Ahuja N, Hackam DJ; Basic Science Committee of the Society of University Surgeons. Ann Surg. 2018 Jun 28. doi: 10.1097/SLA.0000000000002840. PMID:29958227

80. Using Bradford's law of scattering to identify the core journals of pediatric surgery. Desai N, Veras L, Gosain A. J Surg Res. 2018 Sep;229:90-95. doi: 10.1016/j.jss.2018.03.062. PMID:29937022

81. Impaired growth outcomes in children with congenital colorectal diseases. Veras LV, Chotai PN, Tumen AZ, Gosain A. J Surg Res. 2018 Sep;229:102-107. doi: 10.1016/j.jss.2018.03.069. PMID:29936975

82. Association of Comorbidities With Adverse Outcomes After Enterostomy Closure in Premature Neonates. Lucas DJ, Gosain A. JAMA Surg. 2018 May 16. doi: 10.1001/jamasurg.2018.0880. No abstract available. PMID:29799909

83. Extracorporeal Membrane Oxygenation (ECMO) Risk Stratification in Newborns with Congenital Diaphragmatic Hernia (CDH). Jancelewicz T, Brindle ME, Harting MT, Tolley EA, Langham MR Jr, Lally PA, Gosain A, Storgion SA, Kays DW; Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg. 2018 Apr 14. pii: S0022-3468(18)30254-9. doi: 10.1016/j.jpedsurg.2018.04.014. PMID:29754878

84. Using bibliometrics to analyze the state of academic productivity in US pediatric surgery training programs. Desai N, Veras LV, Gosain A. J Pediatr Surg. 2018 Jun;53(6):1098-1104. doi: 10.1016/j.jpedsurg.2018.02.063. PMID:29580787

85. Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis. Johnson CD, Barlow-Anacker AJ, Pierre JF, Touw K, Erickson CS, Furness JB, Epstein ML, Gosain A. FASEB J. 2018 Mar 23:fj201701474RR. doi: 10.1096/fj.201701474RR. PMID:29570391

86. Time to appendectomy for acute appendicitis: A systematic review. Cameron DB, Williams R, Geng Y, Gosain A, Arnold MA, Guner YS, Blakely ML, Downard CD, Goldin AB, Grabowski J, Lal DR, Dasgupta R, Baird R, Gates RL, Shelton J, Jancelewicz T, Rangel SJ, Austin MT. J Pediatr Surg. 2018 Mar;53(3):396-405. doi: 10.1016/j.jpedsurg.2017.11.042. Review. PMID:29241958

87. Ovarian torsion in pediatric and adolescent patients: A systematic review. Dasgupta R, Renaud E, Goldin AB, Baird R, Cameron DB, Arnold MA, Diefenbach KA, Gosain A, Grabowski J, Guner YS, Jancelewicz T, Kawaguchi A, Lal DR, Oyetunji TA, Ricca RL, Shelton J, Somme S, Williams RF, Downard CD. J Pediatr

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88. Pyloric stenosis: an enigma more than a century after the first successful treatment. El-Gohary Y, Abdelhafeez A, Paton E, Gosain A, Murphy AJ. Pediatr Surg Int. 2018 Jan;34(1):21-27. doi: 10.1007/s00383-017-4196-y. Review. PMID:29030700

89. Comprehensive selection of reference genes for quantitative RT-PCR analysis of murine extramedullary hematopoiesis during development. Medrano G, Guan P, Barlow-Anacker AJ, Gosain A. PLoS One. 2017 Jul 21;12(7):e0181881. doi: 10.1371/journal.pone.0181881. eCollection 2017. PMID:28732075

90. Pediatric near-drowning events: do they warrant trauma team activation? Chotai PN, Manning L, Eithun B, Ross JC, Eubanks JW 3rd, Hamner C, Gosain A. J Surg Res. 2017 Sep;217:246. doi: 10.1016/j.jss.2017.06.015. Epub 2017 Jun 27. PMID:28666527

91. Potential effect on molecular pathways in different targeted genes in the VEGF family in retina - From the genomic point of view. Cui J, Liu L, Lu H, Wei D, Jiao Y, Jablonski MM, Williams RW, Gu W, Chen H. Exp Eye Res. 2018 Jun 23. pii: S0014-4835(17)30904-1. doi: 10.1016/j.exer.2018.06.024. [Epub ahead of print] PMID:29944851

92. Evaluation of Detection Methods and Values of Circulating Vascular Endothelial Growth Factor in Lung Cancer. Guo S, Martin MG, Tian C, Cui J, Wang L, Wu S, Gu W. J Cancer. 2018 Mar 22;9(7):1287-1300. doi: 10.7150/jca.22020. eCollection 2018. Review. PMID:29675110

93. Rheumatoid arthritis and periodontal disease: What are the similarities and differences? Li R, Tian C, Postlethwaite A, Jiao Y, Garcia-Godoy F, Pattanaik D, Wei D, Gu W, Li J. Int J Rheum Dis. 2017 Dec;20(12):1887-1901. doi: 10.1111/1756-185X.13240. Epub 2018 Jan 9. Review. PMID:29341486

94. Factors Affecting the Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer. Wang L, Shan B, Gu W. JAMA Oncol. 2018 Feb 1;4(2):263. doi: 10.1001/jamaoncol.2016.6615. PMID:29098276

95. Time-restricted feeding of a high fat diet in C57BL/6 male mice reduces adiposity, but does not protect against increased systemic inflammation. Delahaye LB, Bloomer RJ, Butawan MB, Wyman JM, Hill JL, Lee HW, Liu AC, McAllan L, Han JC, van der Merwe M. Appl Physiol Nutr Metab. 2018 May 2. doi: 10.1139/apnm-2017-0706. PMID:29717885

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96. Delayed Onset of Sleep in Adolescents With PAX6 Haploinsufficiency. Hanish AE, Han JC. Biol Res Nurs. 2018 Mar;20(2):237-243. doi: 10.1177/1099800417753670. PMID:29343077

97. Interdisciplinary Management of Pediatric Obesity: Lessons Learned in the Midsouth. Burton ET, Smith WA, Thurston IB, Gray E, Perry V, Jogal S, Han JC. Clin Pediatr (Phila). 2018 May;57(5):509-518. doi: 10.1177/0009922817730345. PMID:28905651

98. Characteristics of cardiomyopathy in Alström syndrome: Prospective single-center data on 38 patients. Brofferio A, Sachdev V, Hannoush H, Marshall JD, Naggert JK, Sidenko S, Noreuil A, Sirajuddin A, Bryant J, Han JC, Arai AE, Gahl WA, Gunay-Aygun M. Mol Genet Metab. 2017 Aug;121(4):336-343. doi: 10.1016/j.ymgme.2017.05.017. Epub 2017 May 30. PMID:28610912

99. A case for revisiting peer review: Implications for professional self-regulation and quality improvement. Hill TE, Martelli PF, Kuo JH. PLoS One. 2018 Jun 28;13(6):e0199961. doi: 10.1371/journal.pone.0199961. eCollection 2018. PMID:29953510

100. A recurrent de novo missense mutation in UBTF causes developmental neuroregression. Toro C, Hori RT, Malicdan MCV, Tifft CJ, Goldstein A, Gahl WA, Adams DR, Fauni HB, Wolfe LA, Xiao J, Khan MM, Tian J, Hope KA, Reiter LT, Tremblay MG, Moss T, Franks AL, Balak C; C4RCD Research Group, LeDoux MS. Hum Mol Genet. 2018 Apr 1;27(7):1310. doi: 10.1093/hmg/ddy049. PMID:29447355

101. Elevated plasma catecholamines functionally compensate for the reduced myogenic tone in smooth muscle STIM1 knockout mice but with deleterious cardiac effects. Pichavaram P, Yin W, Evanson KW, Jaggar JH, Mancarella S. Cardiovasc Res. 2018 Apr 1;114(5):668-678. doi: 10.1093/cvr/cvy015. PMID:29360991

102. Trafficking of BK channel subunits controls arterial contractility. Leo MD, Jaggar JH. Oncotarget. 2017 Nov 3;8(63):106149-106150. doi: 10.18632/oncotarget.22280. eCollection 2017 Dec 5. PMID:29290926

103. KV channel trafficking and control of vascular tone. Hasan R, Jaggar JH. Microcirculation. 2018 Jan;25(1). doi: 10.1111/micc.12418. Review. PMID:28963858

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104. Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177 Phosphorylation. Zhai X, Leo MD, Jaggar JH. Circ Res. 2017 Sep 1;121(6):650-661. doi: 10.1161/CIRCRESAHA.117.311102. PMID:28696251

105. Models of cytokine dynamics in the inflammatory response of viral zoonotic

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106. Natural infection of Neotropical bats with hantavirus in Brazil. Sabino-

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107. Rate of hepatitis C viral clearance by human livers in human patients: Liver

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108. The role of Syk in peripheral T cells. Park JE, Majumdar S, Brand DD,

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109. The Role of Leukocyte-Associated Ig-like Receptor-1 in Suppressing

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110. Fluorescence Imaging of Mycobacterial Infection in Live Mice Using

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111. Recent advances in cancer outcomes in HIV-positive smokers. Ranjit S,

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112. In vitro evaluation of structural analogs of diallyl sulfide as novel CYP2E1

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113. Sofosbuvir + velpatasvir + voxilaprevir for the treatment of hepatitis C infection. Cory TJ, Mu Y, Gong Y, Kodidela S, Kumar S. Expert Opin Pharmacother. 2018 May;19(7):749-757. doi: 10.1080/14656566.2018.1459567. PMID:29634360

114. Polarized macrophage subsets differentially express the drug efflux transporters MRP1 and BCRP, resulting in altered HIV production. He H, Buckley M, Britton B, Mu Y, Warner K, Kumar S, Cory TJ. Antivir Chem Chemother. 2018 Jan-Dec;26:2040206617745168. doi: 10.1177/2040206617745168. PMID:29343083

115. In vivo evidence for the contribution of peripheral circulating inflammatory

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116. Novel elvitegravir nanoformulation approach to suppress the viral load in

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117. Monocyte-derived exosomes upon exposure to cigarette smoke

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118. Kinetic characterizations of diallyl sulfide analogs for their novel role as

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119. Specific packaging and circulation of cytochromes P450, especially 2E1

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120. Whole-exome sequencing for variant discovery in blepharospasm. Tian J,

Vemula SR, Xiao J, Valente EM, Defazio G, Petrucci S, Gigante AF, Rudzińska-Bar M, Wszolek ZK, Kennelly KD, Uitti RJ, van Gerpen JA, Hedera P, Trimble EJ, LeDoux MS. Mol Genet Genomic Med. 2018 May 16. doi: 10.1002/mgg3.411. [Epub ahead of print] PMID:29770609

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121. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses. Luo J, Xu P, Cao P, Wan H, Lv X, Xu S, Wang G, Cook MN, Jones BC, Lu L, Wang X. Front Mol Neurosci. 2018 Apr 5;11:102. doi: 10.3389/fnmol.2018.00102. eCollection 2018. PMID:29674951

122. In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling

Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration. Geng H, Bu HF, Liu F, Wu L, Pfeifer K, Chou PM, Wang X, Sun J, Lu L, Pandey A, Bartolomei MS, De Plaen IG, Wang P, Yu J, Qian J, Tan XD. Gastroenterology. 2018 Jul;155(1):144-155. doi: 10.1053/j.gastro.2018.03.058. \ PMID:29621481

123. The genetic dissection of Myo7a gene expression in the retinas of BXD

mice. Lu Y, Zhou D, King R, Zhu S, Simpson CL, Jones BC, Zhang W, Geisert EE, Lu L. Mol Vis. 2018 Feb 2;24:115-126. eCollection 2018. PMID:29430167

124. Genetic cartography of longevity in humans and mice: Current landscape

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125. Differential Expression of Hypertensive Phenotypes in BXD Mouse Strains

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126. The cumulative burden of surviving childhood cancer: an initial report from

the St Jude Lifetime Cohort Study (SJLIFE). Bhakta N, Liu Q, Ness KK, Baassiri M, Eissa H, Yeo F, Chemaitilly W, Ehrhardt MJ, Bass J, Bishop MW, Shelton K, Lu L, Huang S, Li Z, Caron E, Lanctot J, Howell C, Folse T, Joshi V, Green DM, Mulrooney DA, Armstrong GT, Krull KR, Brinkman TM, Khan RB, Srivastava DK, Hudson MM, Yasui Y, Robison LL. Lancet. 2017 Dec 9;390(10112):2569-2582. doi: 10.1016/S0140-6736(17)31610-0. PMID:28890157

127. High-Resolution Maps of Mouse Reference Populations. Simecek P, Forejt

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128. Electrocardiographic abnormalities and mortality in aging survivors of

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129. Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular

reactivity, reduced blood pressure and neointima formation. Zou Y, Chen Z, Jennings BL, Zhao G, Gu Q, Bhattacharya A, Cui Y, Yu B, Malik KU, Yue J. Sci Rep. 2018 Jan 23;8(1):1468. doi: 10.1038/s41598-018-19660-z. PMID:29362439

130. Brain Cytosolic Phospholipase A2α Mediates Angiotensin II-Induced

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131. Protection by mTOR Inhibition on Zymosan-Induced Systemic Inflammatory

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132. The role of Syk/IĸB-α/NF-ĸB pathway activation in the reversal effect of BAY

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133. Airway Epithelial Repair by a Prebiotic Mannan Derived from

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134. Successful mesenchymal stem cell treatment of leg ulcers complicated by

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135. Isolation of Primary Murine Retinal Ganglion Cells (RGCs) by Flow

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136. In utero exposure to fine particulate matter results in an altered neuroimmune phenotype in adult mice. Kulas JA, Hettwer JV, Sohrabi M, Melvin JE, Manocha GD, Puig KL, Gorr MW, Tanwar V, McDonald MP, Wold LE, Combs CK. Environ Pollut. 2018 May 22;241:279-288. doi: 10.1016/j.envpol.2018.05.047. PMID:29843010

137. IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic

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138. The natural compound Jatrophone interferes with Wnt/β-catenin signaling

and inhibits proliferation and EMT in human triple-negative breast cancer. Fatima I, El-Ayachi I, Taotao L, Lillo MA, Krutilina R, Seagroves TN, Radaszkiewicz TW, Hutnan M, Bryja V, Krum (Miranda) SA, Rivas F, Miranda-Carboni GA. PLoS One. 2017 Dec 27;12(12):e0189864. doi: 10.1371/journal.pone.0189864. eCollection 2017. PMID:29281678

139. Racial disparities in survival outcomes by breast tumor subtype among

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140. Profiling DNA methylation differences between inbred mouse strains on the

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141. Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging

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142. Retinal Vasculitis and Choroidopathy in Pediatric-Onset Mixed Connective

Tissue Disease. Postlethwaite B, Wynn HG, Pattanaik D, Ost S, MacDonald CB, Walton RC, Kim S, Myers LK, Brown Lobbins M. J Clin Rheumatol. 2017 Oct;23(7):400-401. doi: 10.1097/RHU.0000000000000591. No abstract available. PMID:28937479

143. Destroying the androgen receptor (AR)-potential strategy to treat advanced

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144. Novel Selective Agents for the Degradation of Androgen Receptor Variants

to Treat Castration-Resistant Prostate Cancer. Ponnusamy S, Coss CC, Thiyagarajan T, Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G, Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, Narayanan R. Cancer Res. 2017 Nov 15;77(22):6282-6298. doi: 10.1158/0008-5472.CAN-17-0976. PMID:28978635

145. Loss of Upc2p-Inducible ERG3 Transcription Is Sufficient To Confer Niche-

Specific Azole Resistance without Compromising Candida albicans Pathogenicity. Luna-Tapia A, Willems HME, Parker JE, Tournu H, Barker KS, Nishimoto AT, Rogers PD, Kelly SL, Peters BM, Palmer GE. MBio. 2018 May 22;9(3). pii: e00225-18. doi: 10.1128/mBio.00225-18. PMID:29789366

146. Candidalysin drives epithelial signaling, neutrophil recruitment, and

immunopathology at the vaginal mucosa. Richardson JP, Willems HME, Moyes DL, Shoaie S, Barker KS, Tan SL, Palmer GE, Hube B, Naglik JR, Peters BM. Infect Immun. 2017 Nov 6. pii: IAI.00645-17. doi: 10.1128/IAI.00645-17. [PMID:29109176

147. Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid

Identification of Target-Specific and Physiologically Active Chemical Probes. Butts A, DeJarnette C, Peters TL, Parker JE, Kerns ME, Eberle KE, Kelly SL, Palmer GE. mSphere. 2017 Oct 4;2(5). pii: e00379-17. doi: 10.1128/mSphere.00379-17. eCollection 2017 Sep-Oct. PMID:28989971

148. Overexpression of Candida albicans Secreted Aspartyl Proteinases 2 or 5

is not sufficient for exacerbation of immunopathology in a murine model of vaginitis. Willems HME, Bruner WS, Barker KS, Liu J, Palmer GE, Peters BM. Infect Immun. 2017 Jul 31. pii: IAI.00248-17. doi: 10.1128/IAI.00248-17. PMID:28760935

149. In Vivo Indicators of Cytoplasmic, Vacuolar, and Extracellular pH Using

pHluorin2 in Candida albicans. Tournu H, Luna-Tapia A, Peters BM, Palmer GE. mSphere. 2017 Jul 5;2(4). pii: e00276-17. doi: 10.1128/mSphere.00276-17. eCollection 2017 Jul-Aug. PMID:28685162

150. FoxO1 regulates myocardial glucose oxidation rates via transcriptional

control of pyruvate dehydrogenase kinase 4 expression. Gopal K, Saleme B, Al Batran R, Aburasayn H, Eshreif A, Ho KL, Ma WK, Almutairi M, Eaton F, Gandhi

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151. Secretory phospholipase A2 group IIA modulates insulin sensitivity and

metabolism. Kuefner MS, Pham K, Redd JR, Stephenson EJ, Harvey I, Deng X, Bridges D, Boilard E, Elam MB, Park EA. J Lipid Res. 2017 Sep;58(9):1822-1833. doi: 10.1194/jlr.M076141. PMID:8663239

152. Identification of the KPC plasmid pCY-KPC334: new insights on the

evolution pathway of the epidemic plasmids harboring fosA3-blaKPC-2 genes. Liu J, Xie J, Yang L, Chen D, Peters BM, Xu Z, Shirtliff ME. Int J Antimicrob Agents. 2018 Apr 20. pii: S0924-8579(18)30115-8. doi: 10.1016/j.ijantimicag.2018.04.013. PMID:29684435

153. Complete genomic analysis of multidrug-resistance Pseudomonas

aeruginosa Guangzhou-Pae617, the host of megaplasmid pBM413. Liu J, Li L, Peters BM, Li B, Chen D, Xu Z, Shirtliff ME. Microb Pathog. 2018 Apr;117:265-269. doi: 10.1016/j.micpath.2018.02.049. PMID:29486277

154. Microbial infection pattern, pathogenic features and resistance mechanism

of carbapenem-resistant Gram negative bacilli during long-term hospitalization. Wen S, Feng D, Lu Z, Liu J, Peters BM, Tang H, Su D, Lin YP, Yang L, Xu Z, Shirtliff ME, Chen D. Microb Pathog. 2018 Apr;117:356-360. doi: 10.1016/j.micpath.2018.02.025. Epub 2018 Feb 13. PMID:29452198

155. Novel Mechanism behind the Immunopathogenesis of Vulvovaginal

Candidiasis: "Neutrophil Anergy". Yano J, Peters BM, Noverr MC, Fidel PL Jr. Infect Immun. 2018 Feb 20;86(3). pii: e00684-17. doi: 10.1128/IAI.00684-17. Print 2018 Mar. Review. PMID:29203543

156. Complete sequence of pBM413, a novel multidrug resistance megaplasmid

carrying qnrVC6 and blaIMP-45 from pseudomonas aeruginosa. Liu J, Yang L, Chen D, Peters BM, Li L, Li B, Xu Z, Shirtliff ME. Int J Antimicrob Agents. 2018 Jan;51(1):145-150. doi: 10.1016/j.ijantimicag.2017.09.008. PMID:28923459

157. Complete Sequence of pCY-CTX, a Plasmid Carrying a Phage-Like Region

and an ISEcp1-Mediated Tn2 Element from Enterobacter cloacae. Xu Z, Xie J, Yang L, Chen D, Peters BM, Shirtliff ME. Microb Drug Resist. 2018 Apr;24(3):307-313. doi: 10.1089/mdr.2017.0146. PMID:28876168

158. The viable but nonculturable state induction and genomic analyses of

Lactobacillus casei BM-LC14617, a beer-spoilage bacterium. Liu J, Li L, Peters

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159. Study on spoilage capability and VBNC state formation and recovery of

Lactobacillus plantarum. Liu J, Li L, Li B, Peters BM, Deng Y, Xu Z, Shirtliff ME. Microb Pathog. 2017 Sep;110:257-261. doi: 10.1016/j.micpath.2017.06.044. PMID:28668605

160. A 16-year retrospective surveillance report on the pathogenic features and

antimicrobial susceptibility of Pseudomonas aeruginosa isolates from FAHJU in Guangzhou representative of Southern China. Xie J, Yang L, Peters BM, Chen L, Chen D, Li B, Li L, Yu G, Xu Z, Shirtliff ME. Microb Pathog. 2017 Sep;110:37-41. doi: 10.1016/j.micpath.2017.06.018. PMID:28629721

161. The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction

in glioma. Ganguly D, Fan M, Yang CH, Zbytek B, Finkelstein D, Roussel MF, Pfeffer LM. Oncotarget. 2018 Apr 24;9(31):22095-22112. doi: 10.18632/oncotarget.25188. eCollection 2018 Apr 24. PMID:29774125

162. Lentiviral vector mediated-ASAP1 expression promotes epithelial to

mesenchymal transition in ovarian cancer cells. Zhang T, Zhao G, Yang C, Dong P, Watari H, Zeng L, Pfeffer LM, Yue J. Oncol Lett. 2018 Apr;15(4):4432-4438. doi: 10.3892/ol.2018.7834. Epub 2018 Jan 22. PMID:29541211

163. MicroRNA203a suppresses glioma tumorigenesis through an ATM-

dependent interferon response pathway. Yang CH, Wang Y, Sims M, Cai C, He P, Häcker H, Yue J, Cheng J, Boop FA, Pfeffer LM. Oncotarget. 2017 Dec 6;8(68):112980-112991. doi: 10.18632/oncotarget.22945. eCollection 2017 Dec 22. PMID:29348882

164. The effects of type I interferon on glioblastoma cancer stem cells. Du Z,

Cai C, Sims M, Boop FA, Davidoff AM, Pfeffer LM. Biochem Biophys Res Commun. 2017 Sep 16;491(2):343-348. doi: 10.1016/j.bbrc.2017.07.098. Epub 2017 Jul 18. PMID:28728846

165. Synergism between apolipoprotein E Ɛ4 allele and paraoxonase (PON1)

55-M allele is associated with risk of systemic lupus erythematosus. Tanhapour M, Miri A, Vaisi-Raygani A, Bahrehmand F, Kiani A, Rahimi Z, Pourmotabbed T, Shakiba E. Clin Rheumatol. 2018 Apr;37(4):971-977. doi: 10.1007/s10067-017-3859-3. PMID:29273831

166. Crocin has anti-inflammatory and protective effects in ischemia-reperfusion

induced renal injuries. Yarijani ZM, Pourmotabbed A, Pourmotabbed T, Najafi H.

87


Iran J Basic Med Sci. 2017 Jul;20(7):753-759. doi: 10.22038/IJBMS.2017.9005. PMID:28852439

167. Pediatric and adult dilated cardiomyopathy represent distinct pathological

entities. Patel MD, Mohan J, Schneider C, Bajpai G, Purevjav E, Canter CE, Towbin J, Bredemeyer A, Lavine KJ. JCI Insight. 2017 Jul 20;2(14). pii: 94382. doi: 10.1172/jci.insight.94382. [Epub ahead of print] PMID:28724792

168. GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG

in Green Tea. Pi M, Kapoor K, Ye R, Smith JC, Baudry J, Quarles LD. Mol Nutr Food Res. 2018 Apr;62(8):e1700770. doi: 10.1002/mnfr.201700770. PMID: 29468843

169. Cellular and Molecular Mechanisms of Anti-Phospholipid Syndrome. Radic

M, Pattanaik D. Front Immunol. 2018 May 7;9:969. doi: 10.3389/fimmu.2018.00969. eCollection 2018. Review. PMID:29867951

170. Localized Delivery of Cl-Amidine From Electrospun Polydioxanone

Templates to Regulate Acute Neutrophil NETosis: A Preliminary Evaluation of the PAD4 Inhibitor for Tissue Engineering. Fetz AE, Neeli I, Buddington KK, Read RW, Smeltzer MP, Radic MZ, Bowlin GL. Front Pharmacol. 2018 Mar 28;9:289. doi: 10.3389/fphar.2018.00289. eCollection 2018. PMID:29643810

171. Editorial: NETosis 2: The Excitement Continues. Muñoz LE, Kaplan MJ,

Radic M, Herrmann M. Front Immunol. 2017 Oct 20;8:1318. doi: 10.3389/fimmu.2017.01318. eCollection 2017. No abstract available. PMID:29104572

172. Lactobacillus plantarum prevents and mitigates alcohol-induced disruption

of colonic epithelial tight junctions, endotoxemia, and liver damage by an EGF receptor-dependent mechanism. Shukla PK, Meena AS, Manda B, Gomes-Solecki M, Dietrich P, Dragatsis I, Rao R. FASEB J. 2018 Jun 18:fj201800351R. doi: 10.1096/fj.201800351R. PMID:29912589

173. Phosphorylation hotspot in the C-terminal domain of occludin regulates the

dynamics of epithelial junctional complexes. Manda B, Mir H, Gangwar R, Meena AS, Amin S, Shukla PK, Dalal K, Suzuki T, Rao R. J Cell Sci. 2018 Apr 6;131(7). pii: jcs206789. doi: 10.1242/jcs.206789. PMID:29507118

174. Association between Pulmonary Hypertension and Clinical Outcomes in

Hospitalized Sickle Cell Disease Patients. Agarwal MA, Shah M, Patel B, Nolan VG, Reed GL, Oudiz RJ, Choudhary G, Maron BA. Am J Respir Crit Care Med. 2018 Apr 12. doi: 10.1164/rccm.201802-0261LE. PMID:29648884

88


175. Impact of family history of coronary artery disease on in-hospital clinical outcomes in ST-segment myocardial infarction. Agarwal MA, Garg L, Lavie CJ, Reed GL, Khouzam RN. Ann Transl Med. 2018 Jan;6(1):3. doi: 10.21037/atm.2017.09.27. PMID:29404349

176. Impact of smoking in patients undergoing transcatheter aortic valve

replacement. Agarwal M, Agrawal S, Garg L, Reed GL, Khouzam RN, Ibebuogu UN. Ann Transl Med. 2018 Jan;6(1):2. doi: 10.21037/atm.2017.11.32. PMID:29404348

177. Matrix Metalloproteinase-9 Mediates the Deleterious Effects of α2-

Antiplasmin on Blood-Brain Barrier Breakdown and Ischemic Brain Injury in Experimental Stroke. Singh S, Houng AK, Reed GL. Neuroscience. 2018 Apr 15;376:40-47. doi: 10.1016/j.neuroscience.2017.12.021. PMID:29294343

178. A web-based tool to predict acute kidney injury in patients with ST-elevation

myocardial infarction: Development, internal validation and comparison. Zambetti BR, Thomas F, Hwang I, Brown AC, Chumpia M, Ellis RT, Naik D, Khouzam RN, Ibebuogu UN, Reed GL. PLoS One. 2017 Jul 31;12(7):e0181658. doi: 10.1371/journal.pone.0181658. eCollection 2017. PMID:28759604

179. Disrupted striatal neuron inputs and outputs in Huntington's disease.

Reiner A, Deng YP. CNS Neurosci Ther. 2018 Apr;24(4):250-280. doi: 10.1111/cns.12844. Review. PMID:29582587

180. Neural control of choroidal blood flow. Reiner A, Fitzgerald MEC, Del Mar

N, Li C. Prog Retin Eye Res. 2018 May;64:96-130. doi: 10.1016/j.preteyeres.2017.12.001. Epub 2017 Dec 8. Review. PMID:29229444

181. Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain

Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189. Liu Y, McAfee SS, Guley NM, Del Mar N, Bu W, Heldt SA, Honig MG, Moore BM 2nd, Reiner A, Heck DH. eNeuro. 2017 Aug 18;4(4). pii: ENEURO.0387-16.2017. doi: 10.1523/ENEURO.0387-16.2017. eCollection 2017 Jul-Aug. PMID:28828401

182. Significant transcriptional changes in 15q duplication but not Angelman

syndrome deletion stem cell-derived neurons. Urraca N, Hope K, Victor AK, Belgard TG, Memon R, Goorha S, Valdez C, Tran QT, Sanchez S, Ramirez J, Donaldson M, Bridges D, Reiter LT. Mol Autism. 2018 Jan 27;9:6. doi: 10.1186/s13229-018-0191-y. eCollection 2018. PMID:29423132

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183. Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome: Study Protocol and Early Uses. Ajayi OJ, Smith EJ, Viangteeravat T, Huang EY, Nagisetty NSVR, Urraca N, Lusk L, Finucane B, Arkilo D, Young J, Jeste S, Thibert R; Dup15q Alliance, Reiter LT. JMIR Res Protoc. 2017 Oct 18;6(10):e194. doi: 10.2196/resprot.7989. PMID:29046268

184. Neuronal overexpression of Ube3a isoform 2 causes behavioral

impairments and neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome. Copping NA, Christian SGB, Ritter DJ, Islam MS, Buscher N, Zolkowska D, Pride MC, Berg EL, LaSalle JM, Ellegood J, Lerch JP, Reiter LT, Silverman JL, Dindot SV. Hum Mol Genet. 2017 Oct 15;26(20):3995-4010. doi: 10.1093/hmg/ddx289. PMID:29016856

185. Dental pulp stem cells for the study of neurogenetic disorders. Victor AK,

Reiter LT. Hum Mol Genet. 2017 Oct 1;26(R2):R166-R171. doi: 10.1093/hmg/ddx208. Review. PMID:28582499

186. Shared epitope-aryl hydrocarbon receptor crosstalk underlies the

mechanism of gene-environment interaction in autoimmune arthritis. Fu J, Nogueira SV, Drongelen VV, Coit P, Ling S, Rosloniec EF, Sawalha AH, Holoshitz J. Proc Natl Acad Sci U S A. 2018 May 1;115(18):4755-4760. doi: 10.1073/pnas.1722124115. PMID:29666259

187. Platelet Transfusions in the PICU: Does Disease Severity Matter? Saini A,

West AN, Harrell C, Jones TL, Nellis ME, Joshi AD, Cowan KM, Gatewood CW, Ryder AB, Reiss UM. Pediatr Crit Care Med. 2018 Jun 20. doi: 10.1097/PCC.0000000000001653. [ PMID:29927877

188. Unit conversions between LOINC codes. Hauser RG, Quine DB, Ryder A,

Campbell S. J Am Med Inform Assoc. 2018 Feb 1;25(2):192-196. doi: 10.1093/jamia/ocx056. PMID:28637208

189. LabRS: A Rosetta stone for retrospective standardization of clinical

laboratory test results. Hauser RG, Quine DB, Ryder A. J Am Med Inform Assoc. 2018 Feb 1;25(2):121-126. doi: 10.1093/jamia/ocx046. PMID:28505339

190. Fluorescence-Activated Cell Sorting of Murine Mammary Cancer Stem-Like

Cell Subpopulations with HIF Activity. Brooks DL, Seagroves TN. Methods Mol Biol. 2018;1742:247-263. doi: 10.1007/978-1-4939-7665-2_22. PMID:29330806

191. Chromatin Immunoprecipitation of HIF-α in Breast Tumor Cells Using Wild

Type and Loss of Function Models. Brooks DL, Seagroves TN. Methods Mol Biol. 2018;1742:67-79. doi: 10.1007/978-1-4939-7665-2_7. PMID:29330791

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192. Novel Common Genetic Susceptibility Loci for Colorectal Cancer. Schmit SL, Edlund CK, Schumacher FR, Gong J, Harrison TA, Huyghe JR, Qu C, Melas M, Van Den Berg DJ, Wang H, Tring S, Plummer SJ, Albanes D, Alonso MH, Amos CI, Anton K, Aragaki AK, Arndt V, Barry EL, Berndt SI, Bezieau S, Bien S, Bloomer A, Boehm J, Boutron-Ruault MC, Brenner H, Brezina S, Buchanan DD, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Castelao JE, Chan AT, Chang-Claude J, Chanock SJ, Cheng I, Cheng YW, Chin LS, Church JM, Church T, Coetzee GA, Cotterchio M, Cruz Correa M, Curtis KR, Duggan D, Easton DF, English D, Feskens EJM, Fischer R, FitzGerald LM, Fortini BK, Fritsche LG, Fuchs CS, Gago-Dominguez M, Gala M, Gallinger SJ, Gauderman WJ, Giles GG, Giovannucci EL, Gogarten SM, Gonzalez-Villalpando C, Gonzalez-Villalpando EM, Grady WM, Greenson JK, Gsur A, Gunter M, Haiman CA, Hampe J, Harlid S, Harju JF, Hayes RB, Hofer P, Hoffmeister M, Hopper JL, Huang SC, Huerta JM, Hudson TJ, Hunter DJ, Idos GE, Iwasaki M, Jackson RD, Jacobs EJ, Jee SH, Jenkins MA, Jia WH, Jiao S, Joshi AD, Kolonel LN, Kono S, Kooperberg C, Krogh V, Kuehn T, Küry S, LaCroix A, Laurie CA, Lejbkowicz F, Lemire M, Lenz HJ, Levine D, Li CI, Li L, Lieb W, Lin Y, Lindor NM, Liu YR, Loupakis F, Lu Y, Luh F, Ma J, Mancao C, Manion FJ, Markowitz SD, Martin V, Matsuda K, Matsuo K, McDonnell KJ, McNeil CE, Milne R, Molina AJ, Mukherjee B, Murphy N, Newcomb PA, Offit K, Omichessan H, Palli D, Cotoré JPP, Pérez-Mayoral J, Pharoah PD, Potter JD, Qu C, Raskin L, Rennert G, Rennert HS, Riggs BM, Schafmayer C, Schoen RE, Sellers TA, Seminara D, Severi G, Shi W, Shibata D, Shu XO, Siegel EM, Slattery ML, Southey M, Stadler ZK, Stern MC, Stintzing S, Taverna D, Thibodeau SN, Thomas DC, Trichopoulou A, Tsugane S, Ulrich CM, van Duijnhoven FJB, van Guelpan B, Vijai J, Virtamo J, Weinstein SJ, White E, Win AK, Wolk A, Woods M, Wu AH, Wu K, Xiang YB, Yen Y, Zanke BW, Zeng YX, Zhang B, Zubair N, Kweon SS, Figueiredo JC, Zheng W, Marchand LL, Lindblom A, Moreno V, Peters U, Casey G, Hsu L, Conti DV, Gruber SB. J Natl Cancer Inst. 2018 Jun 16. doi: 10.1093/jnci/djy099. PMID:29917119

193. Designing for impact: identifying stakeholder-driven interventions to support

recovery after major cancer surgery. McMullen C, Nielsen M, Firemark A, Price PM, Nakatani D, Tuthill J, McMyn R, Odisho A, Meyers M, Shibata D, Gilbert S. Support Care Cancer. 2018 Jun 6. doi: 10.1007/s00520-018-4276-0. PMID:29876832

194. Early experience with cytoreduction and hyperthermic intraperitoneal

chemotherapy at a newly developed center for peritoneal malignancy. Guerrero WL, Munene G, Dickson PV, Darby D, Davidoff AM, Martin MG, Glazer ES, Shibata D, Deneve JL. J Gastrointest Oncol. 2018 Apr;9(2):338-347. doi: 10.21037/jgo.2018.01.02. PMID:29755773

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195. Recruitment Techniques and Strategies in a Community-Based Colorectal Cancer Screening Study of Men and Women of African Ancestry. Davis SN, Govindaraju S, Jackson B, Williams KR, Christy SM, Vadaparampil ST, Quinn GP, Shibata D, Roetzheim R, Meade CD, Gwede CK. Nurs Res. 2018 May/Jun;67(3):212-221. doi: 10.1097/NNR.0000000000000274. PMID:29698327

196. NCCN Guidelines Insights: Colon Cancer, Version 2.2018. Benson AB 3rd,

Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF, Garrido-Laguna I, Grem JL, Grothey A, Hochster HS, Hoffe S, Hunt S, Kamel A, Kirilcuk N, Krishnamurthi S, Messersmith WA, Meyerhardt J, Miller ED, Mulcahy MF, Murphy JD, Nurkin S, Saltz L, Sharma S, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Wuthrick E, Gregory KM, Freedman-Cass DA. J Natl Compr Canc Netw. 2018 Apr;16(4):359-369. doi: 10.6004/jnccn.2018.0021. PMID:29632055

197. Molecular Alterations Associated with DNA Repair in Pancreatic

Adenocarcinoma Are Associated with Sites of Recurrence. Ferguson MD, Dong L, Wan J, Deneve JL, Dickson PV, Behrman SW, Shibata D, Martin MG, Glazer ES. J Gastrointest Cancer. 2018 Feb 10. doi: 10.1007/s12029-018-0073-8. PMID:29427136

198. Examining the Durability of Colorectal Cancer Screening Awareness and

Health Beliefs Among Medically Underserved Patients: Baseline to 12 months Post-Intervention. Christy SM, Sutton SK, Gwede CK, Chavarria EA, Davis SN, Abdulla R, Schultz I, Roetzheim R, Shibata D, Meade CD. J Cancer Educ. 2017 Nov 25. doi: 10.1007/s13187-017-1301-9. PMID:29177920

199. Better Late than Never? Adherence to Adjuvant Therapy Guidelines for

Stage III Colon Cancer in an Underserved Region. Guerrero W, Wise A, Lim G, Dong L, Wan J, Deneve J, Glazer E, Dickson P, Daugherty RS, Fleming M, Shibata D. J Gastrointest Surg. 2018 Jan;22(1):138-145. doi: 10.1007/s11605-017-3620-x. PMID:29119529

200. Multiplexed Liquid Chromatography-Multiple Reaction Monitoring Mass

Spectrometry Quantification of Cancer Signaling Proteins. Chen Y, Fisher KJ, Lloyd M, Wood ER, Coppola D, Siegel E, Shibata D, Chen YA, Koomen JM. Methods Mol Biol. 2017;1647:19-45. doi: 10.1007/978-1-4939-7201-2_2. PMID:28808993

201. Impact of body mass index on the short-term outcomes of resected

gastrointestinal stromal tumors. Stiles ZE, Rist TM, Dickson PV, Glazer ES, Fleming MD, Shibata D, Deneve JL. J Surg Res. 2017 Sep;217:123-130. doi: 10.1016/j.jss.2017.05.010. PMID:28595816

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202. Primer in Genetics and Genomics, Article 7-Multifactorial Concepts: Gene-Gene Interactions. Stanfill AG, Starlard-Davenport A. Biol Res Nurs. 2018 May;20(3):359-364. doi: 10.1177/1099800418761098. PMID:29514459

203. Symptom Science: Omics Supports Common Biological Underpinnings

Across Symptoms. McCall MK, Stanfill AG, Skrovanek E, Pforr JR, Wesmiller SW, Conley YP. Biol Res Nurs. 2018 Mar;20(2):183-191. doi: 10.1177/1099800417751069. PMID:29325450

204. The current state of biomarkers of mild traumatic brain injury. Kim HJ, Tsao

JW, Stanfill AG. JCI Insight. 2018 Jan 11;3(1). pii: 97105. doi: 10.1172/jci.insight.97105. Review. PMID:2932137

205. Evaluation of APOE Genotype and Ability to Perform Activities of Daily Living Following Aneurysmal Subarachnoid Hemorrhage. Heinsberg LW, Turi E, Ren D, Crago E, Alexander S, Stanfill AG, Conley YP. Biol Res Nurs. 2018 Mar;20(2):177-182. doi: 10.1177/1099800417746504. PMID:29258400

206. Primer in Genetics and Genomics, Article 7-Multifactorial Concepts: Gene-

Gene Interactions. Stanfill AG, Starlard-Davenport A. Biol Res Nurs. 2018 May;20(3):359-364. doi: 10.1177/1099800418761098. PMID:29514459

207. Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the

Ca2+ Sensitivity of Insulin Secretion Vesicles. Huang C, Walker EM, Dadi PK, Hu R, Xu Y, Zhang W, Sanavia T, Mun J, Liu J, Nair GG, Tan HYA, Wang S, Magnuson MA, Stoeckert CJ Jr, Hebrok M, Gannon M, Han W, Stein R, Jacobson DA, Gu G. Dev Cell. 2018 May 7;45(3):347-361.e5. doi: 10.1016/j.devcel.2018.03.013. PMID:29656931

208. α Cell Function and Gene Expression Are Compromised in Type 1

Diabetes. Brissova M, Haliyur R, Saunders D, Shrestha S, Dai C, Blodgett DM, Bottino R, Campbell-Thompson M, Aramandla R, Poffenberger G, Lindner J, Pan FC, von Herrath MG, Greiner DL, Shultz LD, Sanyoura M, Philipson LH, Atkinson M, Harlan DM, Levy SE, Prasad N, Stein R, Powers AC. Cell Rep. 2018 Mar 6;22(10):2667-2676. doi: 10.1016/j.celrep.2018.02.032. PMID:29514095

209. Compulsive sucrose- and cocaine-seeking behaviors in male and female Wistar rats. Datta U, Martini M, Fan M, Sun W. Psychopharmacology (Berl). 2018 Jun 15. doi: 10.1007/s00213-018-4937-1. PMID:29947917

210. Different functional domains measured by cocaine self-administration under the progressive-ratio and punishment schedules in male Wistar rats. Datta U, Martini M, Sun W. Psychopharmacology (Berl). 2018 Mar;235(3):897-907. doi: 10.1007/s00213-017-4808-1. PMID:29214467

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211. Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase. Brejc K, Bian Q, Uzawa S, Wheeler BS, Anderson EC, King DS, Kranzusch PJ, Preston CG, Meyer BJ. Cell. 2017 Sep 21;171(1):85-102.e23. doi: 10.1016/j.cell.2017.07.041. PMID:28867287

212. Modulation of endoplasmic reticulum stress and the unfolded protein

response in cancerous and noncancerous cells. Purnell MC, Butawan MB, Bingol K, Tolley EA, Whitt MA. SAGE Open Med. 2018 Jun 20;6:2050312118783412. doi: 10.1177/2050312118783412. eCollection 2018. PMID:29977552

213. Reduced oxidative capacity in macrophages results in systemic insulin

resistance. Jung SB, Choi MJ, Ryu D, Yi HS, Lee SE, Chang JY, Chung HK, Kim YK, Kang SG, Lee JH, Kim KS, Kim HJ, Kim CS, Lee CH, Williams RW, Kim H, Lee HK, Auwerx J, Shong M. Nat Commun. 2018 Apr 19;9(1):1551. doi: 10.1038/s41467-018-03998-z. PMID:29674655

214. A Spontaneous Mutation in Taar1 Impacts Methamphetamine-Related

Traits Exclusively in DBA/2 Mice from a Single Vendor. Reed C, Baba H, Zhu Z, Erk J, Mootz JR, Varra NM, Williams RW, Phillips TJ. Front Pharmacol. 2018 Jan 22;8:993. doi: 10.3389/fphar.2017.00993. eCollection 2017. PMID:29403379

215. Teaching with Big Data: Report from the 2016 Society for Neuroscience

Teaching Workshop. Grisham W, Brumberg JC, Gilbert T, Lanyon L, Williams RW, Olivo R. J Undergrad Neurosci Educ. 2017 Nov 15;16(1):A68-A76. eCollection 2017 Fall. PMID:29371844

216. Reproducibility and replicability of rodent phenotyping in preclinical studies.

Kafkafi N, Agassi J, Chesler EJ, Crabbe JC, Crusio WE, Eilam D, Gerlai R, Golani I, Gomez-Marin A, Heller R, Iraqi F, Jaljuli I, Karp NA, Morgan H, Nicholson G, Pfaff DW, Richter SH, Stark PB, Stiedl O, Stodden V, Tarantino LM, Tucci V, Valdar W, Williams RW, Würbel H, Benjamini Y. Neurosci Biobehav Rev. 2018 Apr;87:218-232. doi: 10.1016/j.neubiorev.2018.01.003. Review. PMID:29357292

217. An Integrated Systems Genetics and Omics Toolkit to Probe Gene

Function. Li H, Wang X, Rukina D, Huang Q, Lin T, Sorrentino V, Zhang H, Bou Sleiman M, Arends D, McDaid A, Luan P, Ziari N, Velázquez-Villegas LA, Gariani K, Kutalik Z, Schoonjans K, Radcliffe RA, Prins P, Morgenthaler S, Williams RW, Auwerx J. Cell Syst. 2018 Jan 24;6(1):90-102.e4. doi: 10.1016/j.cels.2017.10.016. PMID:29199021

218. Systems genetics identifies a role for Cacna2d1 regulation in elevated

intraocular pressure and glaucoma susceptibility. Chintalapudi SR, Maria D, Di Wang X, Bailey JNC; NEIGHBORHOOD consortium; International Glaucoma

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Genetics consortium, Hysi PG, Wiggs JL, Williams RW, Jablonski MM. Nat Commun. 2017 Nov 24;8(1):1755. doi: 10.1038/s41467-017-00837-5. PMID:29176626

219. Bayesian association scan reveals loci associated with human lifespan and

linked biomarkers. McDaid AF, Joshi PK, Porcu E, Komljenovic A, Li H, Sorrentino V, Litovchenko M, Bevers RPJ, Rüeger S, Reymond A, Bochud M, Deplancke B, Williams RW, Robinson-Rechavi M, Paccaud F, Rousson V, Auwerx J, Wilson JF, Kutalik Z. Nat Commun. 2017 Jul 27;8:15842. doi: 10.1038/ncomms15842. PMID:28748955

220. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. Quirós PM, Prado MA, Zamboni N, D'Amico D, Williams RW, Finley D, Gygi SP, Auwerx J. J Cell Biol. 2017 Jul 3;216(7):2027-2045. doi: 10.1083/jcb.201702058. Epub 2017 May 31. PMID:28566324

221. CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription. Huang S, Chi Y, Qin Y, Wang Z, Xiu B, Su Y, Guo R, Guo L, Sun H, Zeng C, Zhou S, Hu X, Liu S, Shao Z, Wu Z, Jin W, Wu J. Theranostics. 2018 Apr 3;8(9):2549-2564.

222. Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer. Kumar BNP, Puvvada N, Rajput S, Sarkar S, Mahto MK, Yallapu MM, Pathak A, Emdad L, Das SK, Reis RL, Kundu SC, Fisher PB, Mandal M. Mol Pharm. 2018 Jul 2;15(7):2698-2713. doi: 10.1021/acs.molpharmaceut.8b00218. PMID:29787277

223. Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids. Kong S, Zhang YH, Zhang W. Biomed Res Int. 2018 May 9;2018:2819154. doi: 10.1155/2018/2819154. eCollection 2018. Review. PMID:29854738

224. CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia. Zhang W, Zhang Z, Zhang Y, Naren AP. Int J Mol Sci. 2017 Sep 4;18(9). pii: E1896. doi: 10.3390/ijms18091896. Review. PMID:28869532

II. PRESENTATIONS GIVEN TO PROMOTE CORE USAGE AND LETTERS OF SUPPORT

• The MRC sponsored vendor seminars from Qiagen, Ion Torrent, Affymetrix, 10X Genomics and Illumina.

95


• The MRC conducted laboratory tours and informational sessions for 14 prospective faculty from Pediatrics, Clinical Pharmacy, Anatomy and Neurobiology, Micorbiology, Immunology and Biochemistry, Physiology, and Ophthalmology. The Core Director also provided >70 consultations with clients during this time.

• The Director prepared 13 support letters for grant submissions for eight

independent investigators, one grant was funded (PI: Ashley Stanfill).

III. SUMMARY OF ACTIVITIES A. Personnel

Executive Director: Tiffany Seagroves (5% effort) Director: William Taylor (100% effort) Associate Director: Thomas Cunningham (100% effort) Research Specialist: currently recruiting replacement for Microarray tech. Research Specialist: Lorne Rose (100% effort) Research Specialist: Felicia Waller (100% effort) Business Manager: Natalie Smith (50% effort)

B. Internal Advisory Board (IAB)

P. David Rogers (Clinical Pharmacy, COP), IAB Chair Lu Lu (Genetics, Genomics and Informatics, COM) Lawrence Reiter (Neurology, COM) Ramesh Narayanan (Medicine, COM) Ed Chaum (Opthalmology, COM)

C. Major Equipment (>$5,000)

Equipment MRC Cost

Funding source; Year purchased

Ion Torrent Proton sequencer and server $87,149 MRC/CITG cost-share, $174,298

2013 Ion Torrent PGM sequencer $49,635 MRC/CITG cost-

share, $99,270 2013

Affymetrix Scanner $41,483 MRC/CITG cost-share $80,000

2010 Fluidigm BioMark qPCR system $41,484 MRC/ARRA

funds/VCR, cost-share, $203,149

2010 ABI 3130XL Genetic Analyzer $131,483 MRC

2001 Nanodrop Spectrophotometer $7,153 MRC

2003

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D.Service Contracts

Specialty Underwriters: Cost:

Ion One Touch original system $1,920 Ion One Touch 2.0 System (2 units) $4,366 ABI Genetic Analyzer, 3130XL $9,710 Ion Proton sequencer $16,374 Ion PGM sequencer $4,550 SpectraMax M2E plate reader $3,680 Qiagen Qiacube $1,513 Roche LightCycler 480 (2 units) $7,755 SU total: $49,868 Affymetrix (OEM): Cost: Microarray equipment $42,701 Hamilton Robotics (OEM): Starlet Liquid handling robot $10,153 Total, Service Contracts: $102,722

Zeiss Axiphot Microscope $43,631 Gift 1993

Genepix 4000B Microarray Scanner $55,265 MRC 2001

Qiacube Robot $14,900 MRC 2007

LightCycler 480 qPCR instruments (2) $39,900 MRC 2007

Agilent Bioanalyzer (2) $20,717 MRC/CITG 2002

Light Cycler 480 384-well block $7,500 MRC 2014

Nanodrop 8 sample Spectrophotometer $20,000 MRC 2007

Spectramax M2e Microplate Reader $41,123 MRC 2007

Eppendorf EPmotion Robot $35,500 MRC 2009

Dell Precision T7500 workstation for Partek Software

$10,570 MRC 2011

SWT Dual Xeon Server for Partek Flow Software

$8,359 MRC 2014

Illumina iScan $125,000 COM (Shibata package); 2015

Illumina NextSeq500 $202,000 VC Research 2016

Hamilton Robotics Starlet robot $100,651 VC Research 2017

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E. Advertisement of Core MRC participated in the FY18 new faculty orientation program, provided tours during National Postdoc week, provided tours for prospective and current faculty and sponsored several seminars from companies like Thermo-Fisher, Illumina, and 10X Genomics. Dr. Taylor provided lectures and tours to the BIOE824 class and to PATH804 on behalf of the Course Directors, Drs. Mozhui and Lothstein, respectively.

F. Usage Volumes

FY18 Services: Affymetrix Microarrays: 1,056 chips, 9 UTHSC investigators Illumina Microarays: 16 chips, 1 UTHSC investigator Next-gen library prep: 389 libraries for 7 UTHSC investigators Proton/PGM: 44 runs for 6 UTHSC investigators and 2 external

investigators Agilent Bioanalyzer: 312 chips for 33 UTHSC investigators Illumina (NextSeq): 8 runs for 5 UTHSC and 2 external investigators Sanger sequencing: 7,394 samples for 31 UTHSC investigators and 20

external investigators GeneWiz sequencing: 417 samples for 9 UTHSC investigators Qiacube: 646 samples for 9 UTHSC investigators, 1 external

investigator LC 480 qPCR: 551 runs for 26 UTHSC investigators Transnetyx: 2,912 samples for 20 UTHSC investigators Qbit fluorometer: 502 samples for 11 UTHSC investigators

Use of equipment available at no recharge: Zeiss Axiphot microscope: 155 samples for 3 UTHSC investigators SpectraMax plate Reader: 153 plates for 11 UTHSC investigators Eppendorf EP motion robot: 30 runs for 7 UTHSC investigators Covaris Sonicator: 216 runs for 10 UTHSC investigators

Total volume: 15,341 units of service

G. Multi-year trends Affymetrix Microarrays

Year Usage

FY18 1,056

FY17 735

FY16 396

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Next-Generation Sequencing, library preps

Year Usage

FY18 389

FY17 949

FY16 602

Next-Generation Sequencing, runs

Year Proton, PGM or

NextSeq500platforms

FY18 52

FY17 106

FY16 174

Agilent Bioanalyzer, samples

Year Usage

FY18 312

FY17 279

FY16 257

Sanger sequencing (ABI 3130XL), samples

Year Usage

FY18 7,394

FY17 7,979

FY16 8,773

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GeneWiz (External sequencing vendor), samples

Year Usage

FY18 417

FY17 652

FY16 667*

*New began in FY16

QiaCube automated nucleic acid preparation, samples

Year Usage

FY18 646

FY17 652

FY16 525

LC480 quantitative PCR, runs

Year Usage

FY18 551

FY17 662

FY16 481

Transnetyx genotyping, samples

Year Usage

FY18 2,912

FY17 3,014

FY16 2,685

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Total MRC Revenues, All Services

FY Total

Revenues: FY18 $264,401 FY17 $429,816 FY16 $401,738 FY15 $403,449 FY14 $573,143 FY13 $488,214

H. Fee structure During FY16, the MRC began billing for services on the basis of market pricing for other academic institutions; each FY the prices for services are increased by 3%. In FY18, Affymetrix array costs were either held at FY17 levels, or were slightly reduced to reflect decreased costs of reagents/supplies ordered from this vendor.

Affymetrix Arrays

Product Internal Cost External, Academic

Commercial

Affymetrix Human Gene ST 2.0 $352.00 $423.00 $528.00 Clariom S $231.00 $277.00 $346.00 Clariom D $376.00 $452.00 $565.00 Affymetrix miRNA 4.0 $387.00 $464.00 $580.00

Agilent


Commercial

Agilent DNA High Sensitivity chip $54.00 $65.00 $82.00 Agient RNA Nano Chip $36.00 $43.00 $54.00 Agilent DNA 1000 Chip $36.00 $43.00 $54.00 Agilent RNA Pico Chip $36.00 $43.00 $54.00 Agilent RNA small RNA Chip $45.00 $54.00 $68.00 Agilent DNA 7500 Chip $36.00 $43.00 $54.00

Next Gen Sequencing


Commercial

CHIP-seq libraries $113 $136 $170 Covaris Tubes $5.15 $6.00 $8.00 DNA Libraries $113 $136 $170 Fragment Library $113 $136 $170

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Ion Torrent P1 chips $680 $816 $1019 Ion Torrent PGM 314 Chip $361.00 $433.00 $541 Lexogen RNA-Seq Libraries $155.00 $185.00 $231.00 RNA seq Libraries $155.00 $185.00 $232.00 Nextera Libraries $113 $136 $170

Eppendorf Robot Supplies


Commercial

EpMotion reservoir 30ml $3.09 $3.60 $4.64 Eppendorf 96 deep well plates $5.15 $6.00 $7.70 Eppendorf epTips Motion 1-50, sterile

$7.21 $8.40 $10.82

Fluidigm


Commercial

Fluidigm qdPCR37k digital PCR chip

$113.00 $132.00 $170.00

Fluidigm 48x48 Genotyping $480.00 $560 $720 Fluidigm 48 x 48 Gene Expression

$479.00 $560 $720

Fluidigm 96 sample gene expression chip

$731.00 $852 $1097

LC480


Commercial

LC480 384-well plate $6.00 $7.20 $9.00 LC480 96-well plates $5.00 $6.00 $7.50 LC480 RT-PCR machine Time $10.00 $12.00 $15.00 LC480 SyBr Green Master Mix $49.00 $58.80 $73.50 LC480 TaqMan Master Mix $44.00 $48.40 $52.80 LC480 Transcriptor First Strand Kit

$175.00 $210 $262.50

LC480 UPL probe $8.00 $9.60 $12.00

Qiacube


Commercial

Qiacube, RNA $10.30 $12.36 $15.45 Qiacube, DNA $7.21 $8.65 $10.82 Qiacube, RNA w/o kit $10.30 $12.36 $15.45

Sanger Sequencing

Product Internal Cost External, Commercial

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Academic Sequencing $4.12 $4.94 $6.18 Sequencing- Fragment Analysis $37.08 $44.50 $55.62 Sequencing- Templiphi Preparation

$2.58 $3.09 $3.86

Sequencing, complex/difficult samples

$12.36 $14.83 $18.54

Miscellaneous


Commercial

Qubit, Per sample $1.00 $2.40 $3.00 GeneWiz sequencing $4.00 N/A N/A

IV. GRANTS THAT SUPPORTED THE CORE, FY18

• Williams, Robert o NIH AG043930, Translational Systems Genetics of Mitochondria;

Metabolism; And Aging • Youngentob, Steven

o SUNY Binghamton Subcontract to NIH AA017823, Developmental Exposure Alcohol Research Center

• Gerling, Ivan o NIH DK104155, Defining Islet Heterogeneity Using Single Islet

Transcriptomics • Chauhan, Subhash

o NIH CA210192, Targeted Nanotherapy for Pancreatic Cancer • Chauhan, Subhash

o NIH CA204552, Muc13 Mucin in Colorectal Cancer Health Disparity • Reiner, Anton

o Department of Defense W81XWH-16-1-0076, CB2 Receptor Therapy Using the FDA-Approved Drug Raloxifene to Mitigate Visual Deficits After Mild TBI and/or Ocular Trauma

• Rogers, Phillip o NIH AI058145, Novel Azole Resistance Mechanisms in Candida Albicans

• Rogers, Phillip o NIH AI131620, Upc2A: A Central Regulator and 'Achilles' Heel' of

Fluconazole Resistance in Candida Glabrata • Jaggar, Jonathan

o NIH HL067061, Vascular Control by K+ Channel Trafficking • Jaggar, Jonathan

o NIH HL137745, Endothelial Cell Potassium Channels • Laribee, Ronald

o NIH GM10704005, Mechanisms of Transcription Coregulator Usage by the Target of Rapamycin Pathway

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• Gosain, Ankush o NIH DK098271, Gastrointestinal Mucosal Immune Defects in

Hirschsprung’s Disease • Gosain, Ankush

o NIH DK114543, Validating Intestinal Enteroids to Study Hirschsprung's Associated Enterocolitis

• Hamre, Kristin o NIH AA023508, Maternal Genotype; Choline Intervention; & Epigenetics in

Fetal Alcohol Syndrome • Ledoux, Mark

o NIH NS082296, Genetics and Biology of CIZ1 in Cervical Dystonia • Ledoux, Mark

o Northwestern University Subcontract, A Randomized Double-Blind, Placebo-Controlled, Phase Iia, Parallel Group, Two-Cohort Study to Define the Safety, Tolerability, Clinical and Exploratory Biological Activity of the Chronic Administration of Nilotinib In Participants with Parkinson's Disease

• Lu, Lu o NIH HL128350, Genetic Modulation of Hypertrophic Cardiomyopathy

Severity • Reiter, Lawrence

o Foundation for Prader-Willi Research, Identify Proteome-Wide Differences in Prader-Willi Syndrome Subjects Versus Control Dpsc-Derived Neurons

• Reiter, Lawrence o NIH HD091541, An In Vivo Chemical Screen for Seizure Suppression in

Duplication 15q Syndrome. • Palmer, Glen

o NIH AI099080, Molecular and Chemical Validation of The Vacuole as a New Antifungal Target

• Palmer, Glen o NIH AI127607, Broad Spectrum Antifungals Targeting Fatty Acid

Biosynthesis • Mozhui, Khyobeni

o NIH AG055841, DNA Methylation and Gene Expression Study of Aging and Lifespan Differences

• Chen, Hao o UCSD Subcontract to DA037844, Integrated GWAS of Complex

Behavioral and Gene Expression Traits in Outbred Rats • Cordero-Morales, Julio

o American Heart Association 15SDG25700146, The Role of Bioactive Lipids in Transient Receptor Potential Channels Gating

• Vasquez, Valeria o Israel Binational Science Foundation, Studying Prolonged Nociceptors

Activation by TRPV1 Combining A Spider Toxin and C. Elegans

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• Quarles, Leigh

o NIH AR073518, Polycystins/Taz As A Novel Therapeutic Target to Treat Osteoporosis

• Chizhikov, Viktor o NIH NS093009, Mesenchymal-Neuroepithelial Interactions in the

Developing Telencephalon. • Zhang, Weiqiang

o NIH HL123535, Characterization of an Inhibitory Protein Complex for Cystic Fibrosis Therapy

• Miranda, Susan o NIH AR064354, Determining the Mechanism of How GATA4 Directs

Eralpha Binding in Osteoblasts • Gadiparthi, Rao

o NIH HL069908, NFATs And Vascular Injury • Gadiparthi, Rao

o NIH HL103575, GPCR Signaling and Vascular Wall Remodeling • Myers, Linda

o NIH AR069010, Inhibitory Receptors and Autoimmune Arthritis • Bhattacharya, Sujoy

o Shulsky Foundation Grant, Phenotype Modeling and Therapeutic Approaches to Melas

• Jonsson, Colleen o NIH AI103053, Evolutonary Mechanisms of RNA Virus Host Switching

• Narayanan, Ramesh o GTx Inc - SARDs, Discovery and Development of Novel Selective

Androgen Receptor Degraders (SARDS)-Indollnes, Quinolines, Isoquinollnes, And Carbazoles Structure

• Jablonski, Monica o William & Ella Owens Med Res Foundation, Retinal Inflammasomes

Mediate Ganglion Cell Death in Glaucoma • Dopico, Alejandro

o NIH AA011560, Ethanol Actions on SLO Channels from Arteries vs. Brain • Gu, Weikuan

o Tiantan Hospital Agreement, Center of Integrating Genomics and Bioinformatics for International Study Of Stroke (CIGB-ISS)

• Hori, Roderick o NIH GM118962, The Role of Ubtf In Undiagnosed Neurodevelopmental

Disorders • Cho, Hongsik

o Oxnard Foundation Grant, Novel Targeted Therapy in Early Osteoarthritis Using Innovative Fluorescent Guided Arthroscopy

• Sun, Wen Lin o NIH DA034776, Cocaine Addiction: Neuropharmacological Mechanisms of

Compulsive Cocaine Use

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• Rosloniec, Edward o NIH AR071633, Chimeric Antigen Receptor (CAR) Therapy for

Autoimmune Arthritis • Kumar, Santosh

o NIH DA042374, Exosomes in Tobacco-And HIV-Mediated Neurotoxcity • Rao, Radhakrishna

o NIH DK055532, Intestinal Mucosal Protection by Epidermal Growth Factor • Reiter, Lawrence

o Dup15q Alliance Fellowship Award, Investigation of Synergistic Interactions Among Genes in the 15q Duplication Syndrome

• Bissler, John o Department of Defense W81XWH-14-1-0343-Bissler, Prevention of TSC

Renal Disease • Jonsson, Colleen

o Univ of Louisville Subcontract to NSF 1516011, Collaborative Research: Modeling Immune Dynamics of RNA Viruses in Reservoir and Nonreservoir Species

• Seagroves, Tiffany o Department of Defense, W81XWH-16-1-0061, Targeting Creatine Kinase,

Brain Isoform (CKB) to Inhibit Metastatic Breast Cancer (MBC) • Miranda-Carboni, Gustavo

o Beckman Res Inst-City of Hope-subcobtract to CA189283, Combined Breast MRIi/Biomarker Strategies to Identify Aggressive Biology

• McDonald, Michael o NIH AG054562, Effects of Glycomacropeptide on Memory and Alzheimer-

Related Neuropathology • McDonald, Michael

o NIH NS094595, Effects of Modified Erythropoietin on Cognition and Neuropathology

V. BUSINESS DEVELOPMENT A. Market Assessment

The MRC provides state of the art molecular and genomics resources and facilities for users on the UTHSC campus and other campuses worldwide. We also have the expertise to aid investigators from start to finish in answering their research questions. The typical experiment flows from experimental design to the isolation of nucleic acids to next-generation sequencing (NGS), ending with downstream data analyses through referral to the Molecular Bioinformatics (mBIO) core. Additional in-demand services include robotic DNA/RNA isolation, microarrays offered by Affymetrix, real time qPCR, Sanger sequencing of plasmids and PCR products, and all forms of NGS. Next-generation sequencing services include whole genome, whole exome, whole transcriptome, ChIP-seq, targeting sequencing and de novo genome assembly, among other applications. For all services, the MRC Director and staff are available locally and on demand to answer questions and to provide technical support.

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Overall usage of the MRC declined in FY18 by $164,415 (~40%) as an increasing number of our investigators selected commercial vendors for completing NGS experiments. Decisions about where to peform NGS experiments are primarily price driven, as the MRC does not offer highthroughput NGS platforms that allow pricing to be based on high volume. In particular, decreased use of the MRC by the Department of Genetics, Genomics & Informatics is responsible for the majority of the decline in FY18 revenues. The MRC offers a few pieces of equipment free of charge that may not be available in individual labs including the Nanodrop Spectrophotometer, Spectramax M2e plate reader, the Covaris S2 sonicator, the Genepix microarray scanner, and the Eppendorf EPmotion robot. These items are used predominantly by UTHSC investigators but occasionally by other local labs (U of M, or Rhodes). The MRC added two new large instruments in FY16: 1) the Illumina iScan Microarray Scanner and 2) an Illumina NextSeq500 next-generation sequencer. In FY17, we added the Hamilton Starlet robot system to automate preparation of next-generation sequencing (NGS) libraries, and in FY18, we optimized protocols for using the Starlet to prepare NGS libraries. Although it was predicted that onboarding the iScan and the NextSeq500 instruments would significantly increase our user base, by allowing the MRC to provide relatively inexpensive genotyping and methylation analyses using the iScan, and by meeting demand for the frequently requested Illumina next-generation sequencing pipeline using the NextSeq500, respectively, the instruments were not used to capacity in FY17 or FY18. Customers have been slow to adopt the Illumina NextSeq platform for two reasons: 1) comparisons of new data to legacy data generated on the LifeTech Proton machines are required, or 2) the NextSeq capacity/throughput is too high for users who are profiling small genomes (like fungi, viruses), but is too low/inefficient to perform whole genome DNA-seq experiments for human or rodent samples. We have also lost customers from several PIs based in the GGI Dept. (for DNA-seq applications) to other academic cores or commercial services (like Hudson Alpha, GeneWiz or BGI) who have Illumina Hi-Seq or X10 platforms; the higher throughput of these instruments reduces the per sample price significantly. MRC can compete on turnaround time since our instruments are not used to full capacity, but investigators tend to choose lower price over faster turnaround time. We do not have currently sufficient sample volume at this time on the UTHSC campus to process NGS experiments for research samples to justify investment in a higher-throughput NGS instrument than the NextSeq 500. We are also recently competing with individual labs who have purchased their own “personal” sequencers (such as the PGM, or MiSeq). The iScan instrument was not used at all in FY17, although use by the Shibata laboratory (Dept. of Medicine) began in FY18. Purchase of the iScan by the COM for placement in the MRC was part of the recruitment package for Dr. Shibata.

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Because only the Shibata lab used the iScan throughout FY18, it was relocated from the MRC to the PI lab space as of the Fall of 2018 (FY19). Dr. Shibata will work with the MRC to process other laboratories’ samples, if these assays are requested by other PIs through the MRC. Overall, our user base in FY18 included 91 unique investigators from UTHSC and from 13 external academic institutions or commercial vendors, including 79 investigators based at UTHSC. Many of the external users maintain active collaborations with UTHSC faculty and utilize our services because of the pricing and excellent recommendation from the UTHSC community. We offer a very competitive markup rate for these “Friends of UTHSC” at the MRC, currently 10% above internal rates.

B. Competitive Analysis The MRC is one of three Genomics core labs in the Memphis area. One core, located at St Jude Children’s Research Hospital, does not take outside samples and the other local vendor is commercial (Genome Explorations), and therefore, much more expensive. In addition, there are many commercial services that offer large-scale next generation sequencing services and can provide competitive pricing due to economy of scale (BGI, Beijing, China and HudsonAlpha, Birmingham, AL). However, the value-added of the MRC is direct personal interaction and the ability of the MRC to assist in troubleshooting protocols that these organizations do not provide. In addition, the MRC has a direct pipeline to feed data for analysis by the Molecular Bioinformatics (mBIO) core, which is located adjacent to the MRC in the TSRB Suite 110.

C. Marketing Plans to Obtain New Business

Probably the best marketing a core lab can receive is to have direct recommendations from their clients. We will continue to encourage our clients to tell their collaborators and colleagues about our services; many of our external clients have resulted from such interactions. In order to showcase the MRC, we have, and will also continue to participate in, several campus activities, such as new faculty orientation sessions, participation in Hot Topics seminars, and presentations to postdoctoral fellows and graduate students. As for external advertisement, the MRC website has recently been renovated by the Office of Research and should prove to be more accessible to our clientele and others. Additionally, posters related to MRC services or protocols refined in the MRC were presented at the national ABRF annual meeting in March 2018 and will continue to be presented at local and national meetings, including the regional Southeastern Association of Shared Resources (SEASR) in Atlanta, GA in June of 2019. However, it should be noted that duplication of genomics resources in other departments as part of faculty recruitment packages (including next-generation sequencers provided in startup packages that are to be managed by individual faculty and will not be recharge centers) do pose a direct threat to the continued high demand for NGS technologies.

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D. Forecasted Volumes for New Business Predictions of new business are typically educated guesses based on current trends. Since many new research projects require genomic approaches, internal business should increase on that basis alone. The University has also recruited, and is still recruiting, new faculty, many using genomic techniques, so this effort should also increase campus utilization of the MRC. Increased core usage by new faculty and existing faculty in-house may also lead to increased external usage as users recommend the MRC to external investigators, as a result from collaborations with other institutions. Although total support from grants and contracts for the UTHSC campus increased in FY18 over FY17, the total support from federal sources, which typically fund research performed in core facilities, decreased, which likely contributed to the decrease in MRC revenues in FY18 vs. FY17.

VI. BUDGET FY18 Actual Budget (July 1, 2017- June 30, 2018)

FY2018 DEBITS CREDITS

Salaries/Fringe Benefits $387,419

Supplies $228,013 Service Contracts $102,722 Equipment (> $5,000) $0 Other Expenses $135,030 TOTAL EXPENSES $853,184 FY18 Core Recoveries $264,401 FY18 THEC Appropriation $620,121 TOTAL CREDITS $884,522 Income (Subsidy) $31,338

Income: $31,338, after the THEC appropriation.

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Molecular Bioinformatics (mBIO)

Molecular Bioinformatics Core (mBIO) Institutional Research Core Facility Analysis Report- FY18 Written by Daniel Johnson, PhD; Natalie Smith, MS; and Tiffany N. Seagroves, PhD 1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The mBIO core designation as an institutional core is appropriate since it served 36 total users across multiple departments and Colleges. 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. In FY18, this core processed 661 analysis requests as well as 80.5 hours of custom data mining and scripting from 36 unique users across thirteen departments and three Colleges (COM, COP, and CGHS) as well as external users. The departments with the largest number of users were the Department of Medicine (COM) and the Department of Pharmaceutical Sciences (COP), with twelve and three users, respectively. The top five users, based on the percentage of collected revenues versus total core revenues, were Dr. Dave Rogers (COP, 37.57%), Dr. Mark Miller (COM, 14.63%), Dr. Viktor Chizhikov (COM, 7.38%), Dr. Santosh Kumar (COP, 6.68%) and Dr. Jarrod Fortwendel (COP, 5.60%). 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. 36 unique users were served across multiple departments, Colleges, out-of-state users, and other UT campuses. 4. Can the services for the core be outsourced more economically? No. The internal prices are very competitive relative to other similar academic cores (in bottom tertile), or to commercial vendors. 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led to four PubMed-indexed publications co-authored by Dr. Johnson, 18 letters of support provided for grant applications, and four pending grant applications that included Dr. Johnson as a paid co-PI. In addition, Dr. Johnson provided workshops and seminars related to bioinformatics that were well attended. 6. Is the core currently self-sufficient or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution. The net subsidy was 30.3% of the FY18 budget. Accomplishments this past year: The mBIO core was well-received in its third year of operation as the inaugural institutional molecular bioinformatics core on the UTHSC campus. Dr. Johnson was included as an author on four articles and he supported multiple grant applications. The mBIO interfaced well with the Molecular Resource Center (MRC) and Proteomics and Metabolomics (PMC) institutional cores, establishing a streamlined, collaborative and “one-stop shop”

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approach to support genomics and proteomics experiments from experimental design to data analysis. The mBIO also actively participated in joint staffing sessions with the Biostats, Epidemiology, and Research Design (BERD) clinic referrals to the mBIO core, when appropriate. In FY18, Dr. Johnson served as a member of the proposed STATED advisory board for a new, statewide biostatistics core. Dr. Johnson and Mr. Winston Miller of the mBIO core attended the Midsouth Computational Biology and Bioinformatics Society (MCBIOS) conference at the regional level as well as the Association of Biomolecular Resource Facilities (ABRF) conference at the national level. Dr. Johnson and his student, Mr. Miller, presented their new analysis tool, Extended Automated Bioinformatics Analysis Package System on Chip at both conferences. This presentation was a semi-finalist for the Beckman Award at the ARBF national competition for computational biology tools.

Financial Overview - FY18:

TOTALS FY17 FY18 Revenues 30,006 30,046 Expenses (134,902) (132,520) Income (Subsidy) (104,896) (102,474) Other Costs 0 0 Equipment 0 0 Net Income (Subsidy/Loss) (104,896) (102,474) State Appropriation 68,495 62,302 Net Income (Subsidy/Loss) (36,401) (40,172) Subsidy, % before State Appropriation

78% 77.3%


27% 30.3%

7. Suggested outcomes: It is recommended that mBIO continue as an institutional core.

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Molecular Bioinformatics (mBIO) Institutional Core Facility Summary of Institutional Core Activities for FY 2018 (July 1, 2017- June 30, 2018) I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018) Full-length published articles (UTHSC faculty investigators are indicated in bold font, the Core Director is underlined)

1. Chen H, Sirupangi T, Wu ZH, Johnson DL, Laribee RN. The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function. Sci Rep. 2018 May 25;8(1):8163. doi: 10.1038/s41598-018-26576-1. PMID: 29802328. 2. Ponnusamy S, Coss CC, Thiyagarajan T, Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G, Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, Narayanan R. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2017 Nov 15;77(22):6282-6298. doi: 10.1158/0008-5472. PMID: 28978635. 3. Ponnusamy S, Sullivan RD, You D, Zafar N, He Yang C, Thiyagarajan T, Johnson DL, Barrett ML, Koehler NJ, Star M, Stephenson EJ, Bridges D, Cormier SA, Pfeffer LM, Narayanan R. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy. Hum Mol Genet. 2017 Jul 1;26(13):2526-2540. doi:10.1093/hmg/ddx150. PMID: 28453658. 4. Rybak JM, Dickens CM, Parker JE, Caudle KE, Manigaba K, Whaley SG, Nishimoto AT, Luna-Tapia A, Roy S, Zhang Q, Barker KS, Palmer GE, Sutter TR, Homayouni R,Wiederhold NP, Kelly SL, Rogers PD. Loss of C-5 Sterol Desaturase Activity Results in Increased Resistance to Azole and Echinocandin Antifungals in a Clinical Isolate of Candida parapsilosis. Antimicrob Agents Chemother. 2017 Aug 24;61(9). pii: e00651-17. doi: 10.1128/AAC.00651-17. PMID: 28630186. 5. Popp C, Hampe IAI, Hertlein T, Ohlsen K, Rogers PD, Morschhäuser J. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains. Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: e00584-17. doi: 10.1128/AAC.00584-17. PMID: 28461316. 6. Norton TS, Al Abdallah Q, Hill AM, Lovingood RV, Fortwendel JR. The Aspergillus fumigatus farnesyltransferase β-subunit, RamA, mediates growth, virulence, and antifungal susceptibility. Virulence. 2017 Oct 3;8(7):1401-1416. doi: 10.1080/21505594.2017.1328343. PMID: 28489963.

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7. Al Abdallah Q, Ge W, Fortwendel JR. A Simple and Universal System for Gene Manipulation in Aspergillus fumigatus: In Vitro-Assembled Cas9-Guide RNA Ribonucleoproteins Coupled with Microhomology Repair Templates. mSphere. 2017 Nov 22;2(6). pii: e00446-17. doi: 10.1128/mSphere.00446-17. PMID: 29202040. 8. Al Abdallah Q, Martin-Vicente A, Souza ACO, Ge W, Fortwendel JR. C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus. Front Microbiol. 2018 Mar 26;9:562. doi:10.3389/fmicb.2018.00562. PMID: 29632525. 9. Butts A, Reitler P, Ge W, Fortwendel JR, Palmer GE. Commonly used oncology drugs decrease antifungal effectiveness against Candida and Aspergillus species. Antimicrob Agents Chemother. 2018 Apr 30. pii: AAC.00504-18. doi:10.1128/AAC.00504-18. PMID: 29712657. 10. Tripathi MK, Doxtater K, Keramatnia F, Zacheaus C, Yallapu MM, Jaggi M, Chauhan SC. Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposes. Drug Discov Today. 2018 Apr 23. pii: S1359-6446(18)30071-0. doi: 10.1016/j.drudis.2018.04.010. PMID:29698834. 11. Li JJ, Wang B, Kodali MC, Chen C, Kim E, Patters BJ, Lan L, Kumar S, Wang X,Yue J, Liao FF. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation. 2018 Jan 8;15(1):8. doi: 10.1186/s12974-017-1038-8. PMID: 29310666.

II. Conferences / Presentations

A. Dr. Johnson and Mr. Miller attended the 2017 Midsouth Computational Biology and Bioinformatics Society (MCBIOS) conference and presented the Core’s new automated biostatistical package Automated Bioinfomatics Analysis Package System on Chip (ABAP-SOC). This new package extends the idea of using the Raspberry Pi for bioinformatics and allows the automation of microarray, RNA Seq and Proteomics data analysis. The analysis data is handled by an automated Python and R workflow that starts with alignment and that is completed with biostatistics and publication ready graphics.

B. Dr. Johnson and Mr. Miller attended the national Association of Biomolecular Resource Facilities (ABRF) conference in 2018. They presented the new analysis tools at the national conference. The project was placed into the semifinals in the computational biology category.

III. PRESENTATIONS GIVEN TO PROMOTE CORE RESOURCES AND CORE USAGE

A. Tours 1. Office of Research booth for new faculty 2. Five tours for new postdocs 3. Six individual tours of core for new faculty

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B. Invited Talks 1. “The future of automation and bioinformatics”, Arkansas State University,

Jonesboro, AR 2. “Systems Management for Clinical and Research Data”, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 3. Bioinformatics Seminar Series, University of Memphis, Memphis, TN

C. Courses and Internal Presentations

1. Co-Course Director, PATH942, Web-Based Bioinformatics and Computational Biology Tools (Dr. Johnson also developed the course materials.) 2. Director, Spring 2017 Bioinformatics Workshop Course (Dr. Johnson also developed the course materials.) 3. Molecular Bioinformatics Core presentation for the Department of Microbiology, Immunology, and Biochemistry 4. Molecular Bioinformatics Core presentation for the Cancer Research Building Seminar Series 5. Guest instructor for University of Memphis Bioinformatics course

IV. SUMMARY OF ACTIVITIES

A. Personnel Director: Daniel L. Johnson, Ph.D., Bioinformatics Analyst (staff), 100% effort

Student Assistant: Phillip Winston Miller (MSc. Bioinformatics student, University of Memphis) Started: July 2017, 50% effort (20 hours per week) Staff Bioinformatics Analyst: Phillip Winston Miller (MSc. Bioinformatics), recruited in June 2018 (transitioned to full-time staff after external search)

B. Oversight Committee

The following faculty were members of the FY18 Molecular Bioinformatics Core Internal Advisory Board (IAB):

Lawrence Reiter (Neurology), IAB Chair P. David Rogers (Clinical Pharmacy and Pediatrics) Ramesh Narayanan (Medicine – Hematology) Megan Mulligan (Genetics, Genomics, and Informatics)

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C. Equipment

Equipment currently maintained in the core (all functional):

Equipment Cost Funding Source Analysis Server $3,400 Office of Research Analysis Server $3,400 Office of Research Analysis Server $3,400 Recharge Fees, mBIO Analysis Server $3,400 Recharge Fees, mBIO Deep Storage System $5,400 Office of Research Galaxy Slipstream Server (for individual PIs to access common data analysis tools) $30,000

Office of the Chancellor (initial core investment)

D. Service Contracts No service contracts are needed since all equipment is maintained locally by Dr. Johnson.

E. Usage Volumes by service request type

• Alignment: 94 • Biostatistics: 161 • Custom Scripting: 80.5 • Data Mining: 10 • GraphPad Prism 7 licenses: 32 • Heatmap: 28 • iPathway Guide: 10 • Normalization: 27 • Pearson’s Correlation: 15 • Principle Component Analysis: 15 • Quality Assurance: 231 • SNP Analysis: 8 • String Analysis: 8 • Venn Diagram: 15 • Volcano Plot: 7

Overall usage of the Core Lab:

• 661 requests and 80.5 hours of custom scripting / data mining from 32 PIs, 2 residents, and 2 graduate students from 13 departments were completed in FY 18. This includes COM, COP, and CGHS.

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Departments that requested services FY18:

Medicine: 9 investigators Neurology: 6 investigators MIB: 3 investigators Clinical Pharmacology: 4 investigators Pathology: 3 investigators Pediatrics: 2 investigators Orthopaedic Surgery: 1 investigator Physiology: 1 investigator Pharmaceutical Science: 2 Anatomy and Neurobiology: 1 Graduate Students: 2 Residents: 2 External to UTHSC: 1 investigator

F. Multi-year trends (Bioinformatics)

FY18 was the third full-year of service for the mBIO Core. Although the number of individual projects decreased from FY17, the total core revenues remained flat in FY18. The primary reason for the decrease in project volume is that next-generation sequencing projects completed in the MRC core on campus have decreased. In addition, optimization of analysis workflows built in-house in the mBIO core led to lower overall invoices per project, based on time devoted to each project.

G. Fee Structure

In FY18, per recommendation of the mBIO Internal Advisory Board (IAB), the core moved to a flat-fee schedule rather than an hourly or custom scripting/data mining fee structure. The chart below shows the updated costs associated with each type of service task. Type of service: Cost • Alignment to the genome: $30 per sample • Biostatistics: $30 per paired condition • Custom Scripting: $75 per hour • Data Mining: $75 per hour • GraphPad Prism 7 license: $130 per license • Heatmap analysis: $10 per image • iPathway Guide analysis: $57 per paired condition • Normalization workflow: $50 per experiment • Pearson’s Correlation calculation: $20 per image • Principle Component analysis: $10 per image • Quality Assurance analysis: $20 per sample • SNP Analysis: $75 per sample • String Analysis: $50 per paired condition

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• Venn Diagram: $10 per image • Volcano Plot: $10 per image

V. GRANTS THAT SUPPORTED THE CORE, FY18

• Dave Rogers o NIH AI131620, Novel Azole Resistance Mechanisms in Candida

Albicans o NIH AI058145, UPC2A: A Central Regulator and 'Achilles' Heel' of

Fluconazole Resistance in Candida Glabrata • Santosh Kumar

o NIH AA022063, Role of Cytochrome P450 in Alcohol-Mediated Effects on Antiretroviral and HIV-1

• Ronald Laribee o NIH GM107040, Mechanisms of Transcription Coregulator Usage

by the Target of Rapamycin Pathway • Subhash Chauhan

o NIH CA210192, Targeted Nanotherapy for Pancreatic Cancer o NIH CA204552, MUC13 Mucin in Colorectal Cancer Health

Disparity o NIH CA206069, Development of Targeted Nanotechnology

Platform for Pancreatic Cancer • Ayotunde Dokun

o NIH HL130399, Modulation of mir29A and ADAM12 to Improve Peripheral Arterial Disease Outcomes in Diabetes

• Wen Lin Sun o NIH DA034776, Cocaine Addiction: Neuropharmacological

Mechanisms of Compulsive Cocaine Use • Michael McDonald

o NIH NS094595, Effects of Modified Erythropoietin on Cognition And Neuropathology

• Salvatore Mancarella o NIH HL114869, Stim-Dependent Signaling in Cardiac

Pathophysiology • Raja Shekhar Gangaraju

o Cell Care Therapeutics Contract-Gangaraju • Lawrence Reiter

o NIH HD091541, An In Vivo Chemical Screen for Seizure Suppression In Duplication 15q Syndrome.

• Tiffany Seagroves o METAvivor Research Foundation, Targeting Creatine Kinases to

Inhibit Metastatic Breast Cancer (MBC) • Roderick Hori

o NIH GM118962, The Role of UBTF in Undiagnosed Neurodevelopmental Disorders

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• Michio Kurosu o Cal Tech Subcontract to NIH GM114611, Mechanistic Details of

Key Integral-Membrane Enzymes for Antimicrobial Discovery

Pending Grants • Hao Chen

o NIH/R01 - “Reduced complexity mapping of oxycodone self-administration and stress responsiveness in rats”

• Gustavo A. Miranda-Carboni o NIH/R01 - “Treating Metastatic Chemoresistant Triple Negative

Breast Cancer” • Lawrence T. Reiter

o NIH/R01 - “Therapeutic Compound Discovery for Treatment of Seizures in Dup15q Syndrome”

Salary support of 7% for Dr. Johnson was included in the budget of all pending grants.

VI. BUSINESS DEVELOPMENT A. Market Assessment

In FY18, the mBIO core serviced 651 projects for 32 investigators across three Colleges: COM, COP and CGHS. The core provided e d u c a t i o n a l workshops and one-on-one training to 48 investigators and students. Eleven accounts were created on the Slipstream GALAXY server to allow PIs to perform their own data analysis. The core provided 18 letters of support for extramural grant applications.

We hired one FTE bioinformatics staff member, Mr. Phillip Winston Miller, in June 2018. The core attended the MidSouth Computational Biology and Bioinformatics Society (MCBIOS) and the Association for Biomedical Resource Facilities (ABRF) conferences in order to recruit external customers.

B. Marketing Plans to Obtain New Business

The focus of marketing for the mBIO core in FY19 will be to continue expanding the core customer base throughout the UTHSC system and the Mid-South/Delta region. We will continue participating in events sponsored by the Office of Research, holding seminars and workshops, and expand the mBIO core website. Dr. Johnson presents a series of talks each Spring in order to educate new researchers, and to advertise the mBIO core services. The core will also be working with the new Metabolomics data produced by the new Metabolic Phenotyping Mass Spectrometry (MPMS) unit of the PMC in FY19.

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C. Forecasted Volumes for New Business

The core increased pricing 3% for the FY19 period. This new rate structure became effective July 1, 2018 and continues to place UTHSC in the bottom-half to bottom-third of peer academic institutions that offer bioinformatics services. Based on the IAB recommendations, the core moved to a flat fee structure for all services other than custom scripting and data mining.

In FY17, iPathway Guide, which maps pathway interactomes, was purchased by the mBIO core. The pricing structure was set to charge for individual analyses ($57/project analysis). This new analysis tool can be accessed anywhere online, although Dr. Johnson’s account must make the analysis request. He is then able to share the results with the PIs online.

The external customer markup rate for services will continue to be 50%, which is the rate approved for the mBIO service center, and the rate approved by the Office of Finance in 2017. This level of markup is consistent with other regional cores that offer bioinformatics services to external customers. However, to attract regional extramural customers, we may need to lower the external markup rate to 20-25%.

D. Forecasted Volumes for New Business The core increased pricing 3% for the FY19 period. This new rate structure, which became effective July 1, 2018, continues to place UTHSC in the bottom-half to bottom-third of peer academic institutions that offer bioinformatics services. We continue the trend of sample-based fee rather than hourly rates.

A local deep storage system located in the mBIO core is fully functional for UTHSC-Memphis campus investigators. In addition, Dr. Johnson has been involved with optimizing protocols for data transfer to the Oak Ridge National Laboratories (ORNL) UT-Advance Compute Facility (ACF). He has an approved transfer node to the ACF and he has been trained to access the portal to access computational resources or to store data long-term. However, using the ACF requires coding expertise since it is not currently in a graphical-user-interface (GUI) format for use by the average MRC customer who requests NGS analysis. In FY18, demand for iPathway Guide network mapping software increased as did the resale of Prism (GraphPad) institutional site licenses through the mBIO core (these must be renewed each year).

To obtain external customers, Dr. Johnson will continue to advertise the core at national and regional meetings, including the upcoming Southeastern Association of Shared Resources (SEASR) ABRF regional meeting in June 2019. Overall, it is expected the volume will remain the same in FY20 as in FY19, unless newly recruited faculty begin to use the mBIO core.

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VI. Actual Budget FY18 (July 1, 2017 to June 30, 2018)

FY2018 DEBITS CREDITS Salaries/Fringe Benefits $118,247

Supplies $14,273 Service Contracts $0

Equipment (> $5,000) $0 TOTAL EXPENSES $132,520

FY18 Core Recoveries $30,046 FY18 State Appropriation $62,302

TOTAL CREDITS $92,348 Income (Subsidy) ($40,172)

Subsidy, before State appropriation, % 77.3% Subsidy, after State appropriation, % 30.3%

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Proteomics and Metabolomics (PMC)

Proteomics and Metabolomics (PMC) Institutional Research Core Facility Analysis Report- FY18 Written by David Kakhniashvili, PhD; Natalie Smith, MS; and Tiffany N. Seagroves, PhD 1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The PMC core designation as an institutional core is appropriate since it served multiple investigators from six departments and two Colleges in FY18 and one external, academic customer from Michigan State University. 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. The core served nine independent investigators from six Departments and two Colleges (COM, COP) and one external academic customer. The top five users as a percentage of total core revenues were: Santosh Kumar (26.6%, Pharmaceutical Sciences, COP), Rajendra Raghow (23.3%, Pharmacology, COM), Anna Bukiya (16.0%, Pharmacology, COM), Salvatore Mancarella (10.1%, Physiology, COM) and Elna Saah (8.7%, Michigan State University). 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. The core has been used by six departments within COM, one department within COP and by one external, academic user. In addition, several grants were submitted that proposed to use core services or that incorporated analyzed data generated in the PMC. 4. Can the services for the core be outsourced more economically? No. Based on market-based analysis conducted by Dr. Kakhniashvili in July 2017, the UTHSC core’s prices are within the bottom half to third relative to our academic peer institutions. Only cores with Orbitrap instruments, or equivalent instruments, were compared by Dr. Kakhniashvili. These include the cores located at the Dana Farber/Harvard, the Beth Israel Deaconess Medical Center/Harvard, Duke University, Northwestern University, Yale University/Keck Center, Rochester University, Cornell University, Emory University, Oregon Health Science Center (OHSU) and the University of California San Diego (UCSD). 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting (e.g. grants funded through investigator use, publications, etc.)? Yes. Reviewers of federal grant applications (NIH, Dept. of Defense) expect that investigators have access to proteomics and metabolomics technologies. Data generated in the core led to five manuscripts in FY18, including submission of two manuscripts currently in revision, and three other manuscripts currently in preparation. The core supported 11 grant applications either included core services as essential to complete their proposed scientific aims, or have included preliminary data generated in the core to support their hypotheses; these are detailed in the core activity report. One federal grant from NIH/NIAMS was awarded to M. Elam and R. Raghow.

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Proteomics and Metabolomics (PMC)

6. Is the core currently self-sufficient or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution, with a net subsidy of 20% after the State appropriation. 7. Accomplishments, FY18

• Increased the volume of provided services more than two-fold for internal and external users

• Installed the latest versions of software packages to support advanced proteomics and metabolomics research

• Adapted utilization of longer analytical columns with higher resolving power • The PMC core supported 11 extramural and intramural award applications; one • application was funded, 4 applications are still pending • The PMC core supported 5 manuscripts (2 submitted and in revision and 3 others in

preparation) • Presented seminar entitled “PMC: Instrumentation, Applications, and Services” at the

2017 mBIO Core Bioinformatics Workshop • Led PMC tour for Dr. Zhongjie Sun (new Chair of the Physiology dept.) and lab staff • The PMC participated in the Annual Faculty Recognition and Resource Fair • Director submitted as PI, with the assistance of the IAB Chair, Dr. Heather Smallwood,

a pending S10 grant application to the NIH (Shared Instrumentation Grant, SIG Program) for acquisition of a high-end MS instrument to dedicate to advanced metabolomics and lipidomics research

• Participated in the 2018 annual meeting of the Association of Biomolecular Resource Facilities (ABRF)


TOTALS FY17 FY18 Revenues 26,470 37,827 Expenses (143,921) (163,712) Income (Subsidy) (117,451) (125,885) Other Costs 0 0 Equipment 5,356 0 Net Income (Subsidy) (122,807) (125,885) State Appropriation 90,640 93,360 Net Income (Subsidy) (32,167) (32,525) Subsidy, % before State Appropriation

85% 77%


22% 20%

7. Suggested outcomes: It is recommended that PMC continue as an institutional core.

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Proteomics & Metabolomics (PMC)

Proteomics & Metabolomics Core (PMC) Summary of Institutional Core Activities for FY18 Written by David Kakhniashvili, PhD; Natalie Smith, MS; and Tiffany Seagroves, PhD

I. PUBLICATIONS (where Core Resources have been utilized)

A. Full-length published articles N/A

B. Articles in Press/Preparation There are two manuscripts in revision and three manuscripts in preparation supported by the core.

II. PRESENTATIONS GIVEN TO PROMOTE CORE USAGE 10-2017 Fall 2017 mBIO Core Bioinformatics Workshop Series: “Common

Molecular Tools and Data Analysis Workflow to Accelerate Your Research”

02-2018: Tour for Dr. Zhongjie Sun (incoming Chair of Physiology and staff 04-2018 Annual Faculty Recognition and Resource Fair Research Related Resources – Institutional Research Cores

III.SUMMARY OF ACTIVITIES A. Personnel

Director – David Kakhniashvili, Ph.D. (100% effort) B. Oversight Committee (Internal Advisory Board)

IAB Members: Heather Smallwood, Ph.D. (Pediatrics), IAB Chair Sarka Beranova, Ph.D. (Pharmaceutical Sciences) Ivan Gerling, Ph.D. (Medicine-Endocrinology) Larry Reiter, Ph.D. (Neurology)

C. Equipment Used

Equipment Cost Funding Source Fiscal Year Purchased

Mass Spectrometer – Thermo Fisher Orbitrap Fusion Lumos* + UHPLC units* $1,027150

Office of Research 2016

UHPLC – Thermo Fisher UltiMate 3000 RSLC Nano*

UHPLC – Thermo Fisher Vanquish*

SpeedVac – Thermo Fisher SPD1010-115 $10,629


NanoDrop One – Thermo Fisher $8,984 Office of Research

2016

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Server Computer $6,272 Office of Research

2016 SW – Protein Metrics Bionic $7,700


Micro-centrifuge Legend Micro 21R Sorvall w/RTR $5,356


Total cost of equipment (>$5,000) $1,066,091 *Equipment necessary to launch the core.


Orbitrap and HPLC service contracts: (December 1, 2017 – November 30, 2018)

Service Contract #

Equipment Covered Vendor Cost, $

40235987 Mass spectrometer Orbitrap Fusion Lumos

Thermo Electron North America

52,092.00

UHPLC Ultimate 3000RSLCnano Pump

5,442.00

UHPLC Ultimate 3000RSLCnano Auto-sampler WPS-3000TPL RS

2,450.00

UHPLC Vanquish Pump

3,180.00

UHPLC Vanquish Autosampler

2,635.00

UHPLC Vanquish Column compartment

728.00

Sub-Total 66,527.00 Discount, 10% -6,652.70

Total 59,874.30

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E. Usage Volumes (by Service Type, PI and Department) PI Name Service Types

Service Codes Service Code

Charge per Unit,

$

Units, #

Fees, $

Raghow, R. (Pharmacology)

Sample Preparation Service Codes 101-120

113 200.00 1 200.00 113A 50.00 26 1,300.00 119 1,350.00 3 4,050.00 110 160.00 3 480.00

Diff. Prot. Expr. Analysis Service Codes 500-533

503 140.00 24 3,360.00

PI Total 9,390.00 Bukiya, A. (Pharmacology)


113 200.00 1 200.00 113A 50.00 20 1,000.00 119 1,350.00 2 2,700.00 110 160.00 2 320.00


503 140.00 16 2,240.00

PI Total 6,460.00 Dept. Total 15,850.00

Han, J. (Pediatrics)

Protein ID Service Codes 300-312

301 110.00 3 330.00

302 180.00 1 180.00 †Total †510.00

PI & Dept. Total 510.00 Guntaka, R (MIB)


101

40.00

2

80.00

Protein ID and PTMs Service Codes 401-404

401 110.00 2 220.00

PI Total 300.00 Nishimoto, S. (MIB)

Protein ID Service Codes 300-

312

301 110.00 1 110.00

PI Total 110.00

Dept. Total 410.00

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PI Name Service Types


Charge per Unit,

$

Units, #

Fees, $

Narayanan, R (Medicine)


102 40.00 1 40.00

103 20.00 1 20.00 Protein ID Service Codes 300-312

301 110.00 1 110.00

Total 170.00 Narayanan, R (Medicine)


102 40.00 1 40.00


301 110.00 1 110.00



101 40.00 6 240.00


301 110.00 6 660.00


Sample Preparation 101 40.00 2 80.00 Service Codes 101-120 103 20.00 2 40.00 Protein ID Service Codes 300-312

301 110.00 2 220.00


Sample Preparation 102 40.00 3 120.00 Service Codes 101-120 103 20.00 3 60.00 Protein ID Service Codes 300-312

301 110.00 3 330.00

Total 510.00 PI & Dept. Total 2,210.00

PI Name Service Types Service Codes

Service Code

Charge per Unit,

$

Units, #

Fees, $

Rao, RK. (Physiology)


102 40.00 3 120.00

103 20.00 3 60.00

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Protein ID Service Codes 300-312

301 110.00 3 330.00

Total 510.00 Rao, RK.

(Physiology) Sample Preparation Service Codes 101-120

102 40.00 15 600.00


301 110.00 15 1,650.00

†Total †2,550.00 PI Total 3,060.00

Mancarella, S. (Physiology)


101 40.00 2 80.00


301 110.00 2 220.00

Total 340.00 Mancarella, S. (Physiology


102a 60.00 10 600.00


301 110.00 6 660.00

Total 1,460.00 Mancarella, S. (Physiology


102a 60.00 6 360.00


301 110.00 6 660.00

Total 1,140.00 Mancarella, S. (Physiology


102a 60.00 6 360.00


301 110.00 6 660.00

Total 1,140.00 PI Total 4,080.00

Dept. Total 7,140.00

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PI Name Service Types Service Codes

Service Code

Charge per Unit,

$

Units, #

Fees, $

Kumar, S. (Pharm. Sci.)


113 200.00 1 200.00 113A 50.00 20 1,000.00 119 1,350.00 2 2,700.00 110 160.00 2 320.00


503 140.00 16 2,240.00

Total 6,460.00 Kumar, S. (Pharm. Sci.)


113 200.00 1 200.00 113A 50.00 10 500.00 119 1,350.00 1 1,350.00 110 160.00 1 160.00


503 140.00 8 140.00

Total 3,330.00 Kumar, S. (Pharm. Sci.)


113 200.00 1 200.00 113A 50.00 3 150.00 110 160.00 1 160.00


503 140.00 3 420.00

Total 930.00 PI & Dept.

Total 10,720.00

PI Name Service Types


Charge per Unit,

$

Units, #

Fees, $

Saah, E. (external, MSU)


113 210.00 1 210.00 113A 52.50 10 525.00 119 1,417.50 1 1,417.50 110 168.00 1 168.00


503 147.00 8 1,176.00

Total 3,496.50 PI & Dept.

Total† 3,496.50

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GRAND TOTAL INVOICED, FY18

40,336.50

GRAND TOTAL RECEIVABLES, FY18 †

37,827.00

†: Note: Services were provided to MSU and invoiced in FY18, but payment was not received and credited until FY19 ($3,496.50),

F. Multi-year trends (comparison to previous years) – Internal Users

PI Name (Dept., College)

Usage Volume, $ FY17 FY18

Bukiya, A. (Pharmacology, COM) 0 6,460.00 Raghow, R. (Pharmacology, COM) 550.00 9,390.00

Dept. Total 550.00 15,850.00 Reiter, L. (Neurology, COM) 7,100.00 0

Dept. Total 7,100.00 0 Bissler, J. (Pediatrics, COM) 2,200.00 0

Han, J. (Pediatrics, COM) 0 510.00 Dept. Total 2,200.00 510.00

Waters, C. (Physiology, COM) 300.00 0 Rao, RK (Physiology, COM) 0 3,060.00

Mancarella, S. (Physiology, COM) 4,080.00 Dept. Total 300.00 7,140.00

Wu, Z. (Pathology, COM) 600.00 0 Dept. Total 600.00 0

Narayanan, R. (Medicine, COM) 0 2,210.00 Dept. Total 0 2,210.00

Guntaka, R. (MIB, COM) 0 300.00 Nishimoto, S. (MIB, COM) 0 110.00

Dept. Total 0 410.00 Kumar, S. (Pharm. Sci., COP) 4,190.00 10,720.00

Li, Wei (Pharm. Sci., COP) 440.00 0 Meibohm, B. (Pharm. Sci, COP) 720.00 0

Dept. Total 5,350.00 10,720.00 INTERNAL USERS, VALUE OF SERVICES 16,100.00 36,840.00

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G. Multi-year trends (comparison to previous years) – External Users

PI

Name and Institution Usage Volume, $

FY17 FY18

Vockley, G., University of Pittsburgh 440.00 0

Cowan, A., University of New Mexico 540.00 0

Saah, E., Michigan State University† 0 3,496.50

External Total† 980.00 3,496.50

INTERNAL AND EXTERNAL, TOTAL, FY18† 17,080.00 40,336.50 †: Note: Services were provided to MSU and invoiced in FY18, but payment was not received and credited until FY19.

H. FY18 Service Fee Structure

Sample Preparation Services Service Code

Unit $/unit

Agilent QC test - up to 10 samples per chip 100 per chip 51.50 In-gel trypsin digestion 101 per band 41.20 In-solution trypsin digestion 102 per sample 41.20 In-solution Lys-C/Trypsin digestion 102a per sample 61.80 Reduction/alkylation 103 per sample 20.60 Desalting of peptide mixtures - ZipTip 104 per sample 10.30 Detergent removal/clean-up through acetone precipitation of proteins

105 per sample 20.60

Protein concentration BCA assay in triplicates - at least 3 samples


Peptide (mixture) concentration BCA assay in triplicates - at least 3 samples


High pH Reversed-Phase (HpHRP) Fractionation 8 step fractions


Complete sample processing starting from cleared cell lysate, membrane pellets, or cell pellets

Processing for following LC/MS/MS analysis 111 set-up 206.00 111a per sample 51.50

Processing for following label-free differential protein expression analysis

112 set-up 206.00 112a per sample 51.50

Processing for following TMT/iTRAQ 113 set-up 206.00

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labeling 113a per sample 51.50 TMT/iTRAQ labeling/preparation for LC and MS analysis, 4-plex (set of 4 samples)

114 per set 721.00

TMT/iTRAQ labeling/preparation for LC and MS analysis, 6-plex (set of 6 samples)

116 per set 1030.00


118 per set 1287.50


119 per set 1390.50

Mass Spectrometry Services - Direct Infusion

Determination of the Molecular Mass

Infusion ESI-HRAM MS analysis - small analyte


Intact protein


Identification of Small Analyte

Infusion ESI-MS/MS analysis, spcified transition


Mass Spectrometry Services - Proteomics

Protein Identification

LC/MS/MS, DB search (does not include sample digestin/preparation)

RP LC/MS/MS - 30 min gradient 300 per sample 72.10 RP LC/MS/MS - 60 min gradient 301 per sample 113.30 RP LC/MS/MS - 120 min gradient 302 per sample 185.40 RP LC/MS/MS - 240 min gradient 304 per sample 309.00 MudPIT, DB search (does not include sample digestin/preparation)

6 (SCX or HpHRP) step fractions – 2 hr RP-LC/MS/MS per fraction

310 per fraction 144.20

7-12 (SCX or HpHRP) step fractions – 2 hr RP-LC/MS/MS per fraction


>12 (SCX or HpHRP) step fractions – 2 hr RP-LC/MS/MS per fraction


Protein Identification and Mapping of Specified PTMs

LC/MS/MS, DB/PTM search (does not include sample digestin/preparation)

RP LC/MS/MS - 60 min gradient 401 per sample 113.30 RP LC/MS/MS - 120 min gradient 402 per sample 185.40

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RP LC/MS/MS - 240 min gradient 403 per sample 309.00 Search for specified PTMs 404 per PTM 30.90 Differential Protein Expression Analysis - iTRAQ/TMT Based Analysis (Reporter Ion quantification)

LC/MS/MS, DB search/quantification (does not include sample labeling/preparation)

Unfractionated mixture of labeled peptides – 2 hr RP-LC/MS/MS

500 per run 206.00


510 per run 339.90

MudPIT, DB search/quantification (does not include sample labeling/preparation)







Differential Protein Expression Analysis - SILAC Analysis (Precursor Ion Quantification)

LC/MS/MS, DB search/quantification (does not include sample labeling/preparation)


500 per run 206.00


510 per run 339.90

MudPIT, DB search/quantification (does not include sample labeling/preparation)







Differential Protein Expression Analysis - Label Free Analysis (Precursor ion Peak Area Detection)

RP-LC/HRAM-MS/MS, post-acquisition analysis (does not include sample digestion/preparation)

RP-LC/HRAM-MS/MS - 120 min gradient 521 per run 206.00 RP-LC/HRAM-MS/MS - 240 min gradient 522 per run 339.90 Absolute Quantification of Specified (Target) Proteins - Parallel Reaction Monitoring (PRM)

PRM analysis for peptide quantification (does not include sample digestin/preparation)

RP LC/MS/MS, post-acquisition analysis, Peptide Internal Standard, AUC quantification

RP LC/MS/MS - peptide quantification, 30 min gradient

531 per run 82.40

RP LC/MS/MS - peptide quantification, 532 per run 128.75

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60 min gradient RP LC/MS/MS - peptide quantification, 120 min gradient

533 per run 206.00

Mass Spectrometry Services - Metabolomics

Absolute Quantification of Specified Metabolyte/Small Molecule

LC/MS/MS, post-acquisition analysys, Calibration Curve, Internal Standard, AUC Quantification

Internal and calibration standards are provided by the customer

Standard Run - LC/MS/MS 15 min gradient 601 per run 17.51 Extended Run - LC/MS/MS 30 min gradient 602 per run 30.90 Differential Quantitative Profiling of Metabolytes - Untargeted Analysis

LC/HRAM-MS/MS, post-acquisition analysis, HRAM AUC Quantification, MS/MS identification

Standard Run - LC/HRAM-MS/MS 15 min gradient

611 per run 30.90

Extended Run - LC/HRAM-MS/MS 30 min gradient

612 per run 51.50

Finding Expected Compound/Transformation - Targeted Analysis

RP-LC/HRAM-MS/MS, post-acquisition analysis, MS/MS identification

Standard Run - LC/HRAM-MS/MS 15 min gradient

621 per run 30.90

Extended Run - LC/HRAM-MS/MS 30 min gradient

622 per run 51.50

IV. GRANTS THAT SUPPORT THE CORE A. Grants and Contracts That Supported the Core in FY18

Kumar, Santosh o NIH AA022063, Role of Cytochrome P450 in Alcohol-Mediated Effects on

Antiretroviral and HIV-1 Rao, Radhakrishna

o NIH DK055532, Intestinal Mucosal Protection by Epidermal Growth Factor Mancarella, Salvotore

o NIH HL114869, Stim-Dependent Signaling in Cardiac Pathophysiology Narayanan, Ramesh

o GTx Inc., Discovery and Development of Novel Selective Androgen Receptor Degraders (SARDs)-Indollnes, Quinolines, Isoquinollnes, and Carbazoles Structure

Han, Joan o Jackson Laboratory Subcontract to NIH DK102918, Modulation of AGRP

Neuronal Excitability: Role Of Diet And Body Weight

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Guntaka, Ramareddy o Sudershan Biotech contract, Cloning and Characterization of Hepatitis C

Virus and Therapeutic Proteins Lowe, Tao

o NIH EY023853, Nanogels for Drug Delivery Across the BBB to Treat Diabetic Retinopathy

Sun, Wen Lin o NIH DA034776, Cocaine Addiction: Neuropharmacological Mechanisms of

Compulsive Cocaine Use

B. Letters of support were provided for 11 grant applications including: New Grant Awards: Raghow, R. and Elam, M.

o NIH/NIAMS AR074018, Metabolomics of Statin-induced Myalgia Pending Grant Applications: 1. Zhao, Qi

“Identification of Novel Metabolites for Osteoporosis Risk” NIH

2. Jablonski, Monica “Extended release formulation of a new IOP lowering drug for improved treatment of glaucoma” NIH

3. Reiter, Lawrence “Therapeutic Compound Discovery for Treatment of Seizures in Dup15q Syndrome” NIH

4. Chen, Hao “Reduced complexity mapping of oxycodone self-administration and stress responsiveness in rats” NIH Grant Applications to be Resubmitted

1. Quarles, Leigh. Darryl “Discovery of an Osteocalcin Sensing GPCR Regulating Tissue-Specific Metabolic Functions and Inter-Organ Communications” NIH

2. Mancarella, Salvatore “Role of Orai proteins during pathological cardiac remodeling” NIH

3. Smallwood, Heather “Preclinical Development of a Host Targeting Metabolic Drug for Antiviral Therapy” NIH/NIAID

4. Smallwood, Heather “A Role for Epithelial Metabolic Signaling in Human Respiratory Infection” NIH/NIAID

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5. Davenport, Athena “MicroRNA-based epigenetic approach to induce fetal hemoglobin” NIH

6. Atherton, Jim “Uremic Toxin Levels in Pediatric End-Stage Renal Disease” Le Bonheur’s Children’s Hospital Research Grant

V. BUSINESS DEVELOPMENT PLAN

A. Market Assessment The Vice Chancellor for Research, Dr. Steven Goodman, created the new Proteomics and Metabolomics Core (PMC) in FY2016 to meet the needs of the basic and clinical researchers at UTHSC and to help develop the Precision Medicine initiative on campus. The primary mission of the newly established institutional core was to provide investigators at UTHSC, in the Memphis area and regionally/nationally with access to state of the art proteomics, metabolomics, lipidomics and glycomics technologies and services. In December 2015, the Director of the PMC core was hired and the Thermo Orbitrap Fusion Lumos MS and two high- performance liquid chromatography (HPLC) systems (Vanquish and Nano) were installed. Together, these instruments are capable of sensitively profiling changes in proteins, metabolites and their modifications, making it possible to compare these pathways to system-wide changes previously observed at the genomic and transcriptomic levels. The PMC core is defined as an institutional core based on its potential to serve faculty in multiple Colleges and departments within UTHSC. The potential customers for our base include UTHSC, U of Memphis, the VA, Le Bonheur Hospital, the West Cancer Center, and other commercial and academic partners in the Memphis metropolitan area. Investigators from St. Jude are also potential customers since the queue for their internal proteomics core is currently several weeks long. Our core also has capacity to analyze samples for regional/national academic or commercial customers, and we served two external universities in FY17 and one external university in FY18.

B. Competitive Analysis

Typically, the biggest threats to proteomics and metabolomics cores are other academic core facilities that accept external samples, regional NIH NIH-funded Regional Comprehensive Metabolomics Resource Cores (RCMRCs), and, particularly for metabolomics, commercial vendors like Metabolon. The PMC core offers value-added services that include the scientific expertise and breadth of training of the Director, quick turnaround time and state of the art instrumentation that most core facilities in the United States have not yet adopted. The PMC core is also a highly desired campus resource of several newly recruited faculty, or candidates who have recently interviewed for key positions on our campus, including Department Chairs and the Director for Research for the West Cancer Center. The closest proteomics core facility is

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located at St. Jude Children’s Hospital, which is available for use only by those UTHSC faculty who directly collaborate with St. Jude investigators.

C. Marketing Plans to Obtain New Business A primary focus of the PMC core will be to continue advertisement of core services to the UTHSC campus, throughout the Memphis Medical Center and throughout the University of Tennessee system. The branding strategy will involve enhanced local advertisement on the campus, participation in the Hot Topics in Research seminar series, participation in Office of Research-sponsored institutional “Core Days”, development of a new PMC website by the Office of Research, which launched in November 2017, and development of new print materials, including a comprehensive Institutional Core brochure and specific PMC core workshop print advertisements to be posted around campus. In addition, PMC will host Open Houses for users to tour the facility and to meet new core staff, and will develop workshops for the UTHSC campus focused on proteomics and metabolomics technology and protocol development and design. The PMC core will also host seminars by commercial vendors to advertise onboarding of new equipment or to educate users about new proteomics approaches and technologies (such as iTRAQ, MudPIT). The Director will also continue to schedule individual presentations to departments to directly advertise core capabilities to the faculty. New business will also be generated from the addition of the Metabolic Phenotyping Mass Spectrometry (MPMS) unit of the PMC beginning in FY19, directed by Dr. Michelle Puchowicz (Dept. of Pediatrics). The MPMS unit will provide targeted metabolomics services as part of the PMC such that the Lumos Orbitrap MS can be left in a proteomics profiling mode, without “flipping” the instrument to a metabolomics mode, as per the recommendation of the PMC Internal Advisory Board (IAB). This recommendation was made after discovering that the instrument failed every time a “flip” was executed. To expand core services further, Dr. Kakhniashvili served as PI on a S10 instrumentation grant proposal prepared in FY18 with the purpose to acquire a second dedicated MS instrument for the PMC for untargeted metabolomics profiling to support discovery-based research projects. The S10 application will be reviewed in October 2018.

D. Forecasted Volumes for New Business

In FY19, we project that internal recoveries from PMC proteomics-based services will increase 25% over FY18 levels, based on estimated demand and knowledge of upcoming projects by the Director. In addition, as outlined in the FY18-FY20 core business plans, the MPMS unit of the PMC is expected to generate approximately $40,000 in revenues per fiscal year once the MPMS unit is fully operational. As of Q1 of FY19, the Agilent GC/MS instrument housed by the MPMS unit is being evaluated for quality control, and revenues for these services are not expected until Q2 of FY19.

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VI. Actual Budget FY18 (July 1, 2017 to June 30, 2018)

FY2018 DEBITS CREDITS Salaries/Fringe Benefits $93,317 Supplies $10,521 Service Contracts/Maintenance $59,874 Equipment (> $5,000) $0 TOTAL EXPENSES $163,712 FY18 Internal Recoveries FY18 External Recoveries

$34,330 $3,497

FY18 State Appropriation $ 93,360 TOTAL CREDITS $131,187 Income (Subsidy) ($32,525)

Subsidy, %, before State appropriation: 77% Subsidy, %, after State appropriation: 20%

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Flow Cytometry and Cell Sorting (FCCS)

Flow Cytometry and Cell Sorting (FCCS) Institutional Research Core Facility Analysis Report- FY18 Written by Tony Marion, PhD; Natalie Smith; and Tiffany N. Seagroves, PhD

1. Relative to a specific core’s mission, is the designation as an “institutional core”appropriate?The FCCS core designation as an institutional core is appropriate since it served 36 totalusers across 25 laboratories representing 11 departments and 4 Colleges.

2. Does the Core pass the multi-departmental, multi-investigator litmus test.Yes. In FY18, this core processed 193 cytometry projects and 29 flow sorting projects from36 unique users (25 labs) across 11 departments and four Colleges (COM, COP, COD andCON). The Department with the largest number of unique users was the Department ofMicrobiology, Immunology and Biochemistry (MIB, COM) with 9 unique laboratories. Thetop five users, based on the percentage of collected revenues per PI versus core revenues,accounted for 61.19% of total revenues. These investigators were: 1) Mark A. Miller (MIB,COM, 19.47%), 2) Marko Radic (MIB, COM, 13.61%), 3) Ankush Gosain (Surgery, COM,11.95%), 4) Vanessa Morales-Tirado (Ophthalmology, COM, 8.50%) and 5) ElizabethFitzpatrick (MIB, COM, 7.67%). The other 20 labs accounted for 38.81% of revenues.

3. Is there sufficient intra- and inter-departmental use and if not, why?Yes. 36 unique users were served across multiple Departments and Colleges.

4. Can the services for the core be outsourced more economically?No. It should also be noted that live, stained cells cannot be shipped to other cores forFACS analysis or cell sorting, and must be processed locally.

5. Are there unaccounted benefits beyond fiscal consideration to warrant continuedinstitutional underwriting (e.g. grants funded through investigator use, publications,etc.)?Yes. In FY18, core activities led to at least 8 PubMed-indexed publications and supported19 awarded extramural grants/contracts and multiple intramural grants or startup fundingpackages. Reviewers of federal grant applications (NIH) expect that the investigators haveaccess to flow cytometry facilities. In addition, hands-on cytometry training was provided toeleven new users.

6. Is the core currently self-sufficient, or is it subsidized by the Institution?In FY18, the core was subsidized by the Institution, not including salary of the Director,which was entirely provided by the Department of Microbiology, Immunology andBiochemistry. Overall, FY18 ended with a net subsidy of $137,202.

Accomplishments this past year: • The FCCS core supported multiple publications, abstract presentations and

extramural and intramural awards.• Dr. Tony Marion, FCCS Core Director, hosted a regional comprehensive flow

cytometry

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• course for research professionals representing multiple research platforms. Thecourse was presented by FloCyte in association with the annual Southeast FlowCytometry Interest Group (SEFCIG) meeting.

• Dr. Tony Marion hosted the annual SEFCIG meeting. SEFCIG is a regional resourceto promote research, development, and applications in analytical cytometry for theSoutheast region.

• Dr. Tony Marion will continue as Vice-President and member of the ExecutiveCouncil for SEFCIG.

• Dr. Deidre Daria replaced Dr. Terry-Ann Milford as the Flow Cytometry Specialist inApril 2018. Dr. Daria has an outstanding background and experience in flowcytometry and cell sorting from her graduate school training for the Ph.D.,Universitätsklinikum Ulm Institut für Experimentelle Tumorforschung, Ulm,Germany; her post-doctoral training and experience at Battelle Biomedical ResearchCenter; and as a Researcher at Battelle.

• In April/May 2018, Dr. Deidre Daria attended the Shared Resource Laboratory-FlowCytometry seminar series offered through CYTO University (cytometry educationoffered through ISAC: International Society for Advancement of Cytometry).


TOTALS FY17 FY18 Revenues 24,320 28,892 Expenses* (75,999) (166,094) Income (Subsidy) (51,679) (137,202) Other Costs 0 0 Equipment 286,592 0 Net Income (Subsidy) (338,271) (137,202) Subsidy, %* 93%* 82.6%

*Dr. Tony Marion’s salary is entirely subsidized by the MIB. Dr. Terry-Ann Milford began inthe newly created Flow Cytometry Specialist position at the start of Q4 of FY17 and shevacated the position at the end of FY18. To facilitate cross-training in core services, theincoming Flow Cytometry Specialist salary (Dr. Deidre Daria) over-lapped with the outgoingFlow Cytometry Specialist salary (Dr. Milford) for two months during May/June 2018. Inaddition, during FY17, the ZE5 cytometer was initially covered under the OEM warranty;however, in FY18, a yearly maintenance agreement with BioRad was purchased for$27,000/year.

7. Suggested outcomes:It is recommended that FCCS continue as an institutional core.

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Flow Cytometry and Cell Sorting (FCCS) Institutional Core Facility Summary of Institutional Core Activities for FY18 Written by Deidre Daria, PhD; Tony Marion, PhD; Natalie Smith, MS; and Tiffany N. Seagroves, PhD I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018) Full-length published articles (UTHSC faculty investigators are indicated in bold font) 1. Periasamy R, Elshaer SL, Gangaraju R. CD140b (PDGFRβ) signaling in adipose-

derived stem cells mediates angiogenic behavior of retinal endothelial cells. Regenerative Engineering and Translational Medicine, 2018.

2. Kotla S, Singh NK, Kirchhofer D, Rao GN. Heterodimers of the transcriptional factors NFATc3 and FosB mediate tissue factor expression for 15(S)-hydroxyeicosatetraenoic acid-induced monocyte trafficking. J Biol Chem. 2017 Sep 8;292(36):14885-14901.

3. Toro C, Hori RT, Malicdan MCV, Tifft CJ, Goldstein A, Gahl WA, Adams DR, Harper F, Wolfe LA, Xiao J, Khan MM, Tian J, Hope KA, Reiter LT, Tremblay MG, Moss T, Franks AL, Balak C; C4RCD Research Group, LeDoux MS. A recurrent de novo missense mutation in UBTF causes developmental neuroregression. Hum Mol Genet. 2018 Feb 15;27(4):691-705.

4. Zhu X, Liu J, Yu Z, Chen CA, Aksel H, Azim AA, Huang GT. A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue. Tissue Engineering Part C: Methods 2018 Feb;24(2):108-120.

5. Aksel H, Huang GTJ. Combined effects of vascular endothelial growth factor and bone morphogenetic protein 2 on odonto/osteogenic differentiation of human dental pulp stem cells in vitro. Journal of Endodontics. 2017 Jun;43(6):930-935.

6. Goldsmith ZK, Coppess W, Irvine AS, Yuan K, Barsh SR, Ritter MK, McEwen MW, Flores-Otero J, Garcia-Vargas A, Martinez-Ferrer M, Brennan RC, Morales-Tirado VM, Wilson MW. Targeting the Platelet-Derived Growth Factor-beta Stimulatory Circuitry to Control Retinoblastoma Seeds. Invest Ophthalmol Vis Sci, 2018.

7. Chintalapudi SR, Patel NN, Goldsmith ZK, Djenderedjian L, Wang XD, Marion TN, Jablonski MM, Morales-Tirado VM. Isolation of Primary Murine Retinal Ganglion Cells (RGCs) by Flow Cytometry. J Vis Exp. 2017 Jul 5;(125).

8. Wang W, Zhang B, Mani AM, Wu Z, Fan Y, Li W, Wu ZH. Survivin inhibitors mitigate chemotherapeutic resistance in breast cancer cells by suppressing genotoxic NF-kappaB activation. J Pharmacol Exp Ther. 2018; 366:184-193.

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II. PRESENTATIONS AND MEETINGS TO PROMOTE CORE USAGE AND FUNCTION A. Flow cytometry courses

In FY18, Dr. Tony Marion, hosted a regional comprehensive flow cytometry course in conjunction with FloCyte Associates, which covered topics such as compensation, multiparameter flow cytometry, and assay design. More than ten research professionals attended the course representing multiple research platforms ranging from educational institutes and hospitals to private industry, including the University of Tennessee Health Science Center, St. Jude Children’s Research Hospital, and three biotechnology companies.

B. Meetings to support core functions and instrumentation In 2017, Dr. Marion was elected Vice-President of the Southeast Flow Cytometry Interest Group (SEFCIG), a professional organization associated with the International Society for Advancement of Cytometry (ISAC) which promotes research, development, and applications in analytical cytometry. In April of 2018, Dr. Marion hosted SEFCIG in Memphis which provided an excellent opportunity to showcase our core facility to the meeting attendees. The SEFCIG meeting neither depended upon, nor expected, financial or space commitment from the hosting institution. SEFCIG members at the hosting institution were only requested to assist in identifying and inviting potential speakers. Likewise, no institutional commitment was required to support housing or honoraria costs for invited speakers. The program included more than 20 talks with topics ranging from managing shared resource laboratories, new techniques in flow cytometry, and primary research centered around flow cytometry including research performed at UTHSC. More than 50 people attended the meeting, including Dr. Terry-Ann Milford, Dr. Deidre Daria, and Dr. Tony Marion from the UTHSC FCCS Core. A number of UTHSC and SJCRH staff, students, postdocs, and faculty also attended the meeting. The FCCS core participated in the annual Faculty Fair & Recognition event in Spring of 2018.

C. Training

Eleven new UTHSC users were trained in flow cytometry, representing users from five departments within two Colleges at UTHSC. Currently, about 83% of our users prefer user-operated cytometry following their hands-on training, and 17% of users choose to request assistance of the core to acquire their samples. Of note, training in post-acquisition data analysis using the FlowJo analysis software is now also offered on an as-needed basis free of charge through the FCCS core facility. This offering should accelerate dissemination of results in grant applications and in publications.

III. SUMMARY OF ACTIVITIES

A. Personnel Scientific Director: Tony Marion, Ph.D., Professor (40% effort)

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Technical Director: Terry-Ann Milford, Ph.D., Research Specialist (100% effort through May FY18). Technical Director: Deidre Daria, Ph.D., Research Specialist (100% effort April FY18-present).

B. FCCS Internal Advisory Board (IAB)

The FY18 FCCS Core Advisory Committee consists of the following members: Elizabeth Fitzpatrick (MIB, COM), IAB Chair David Brand (Medicine-Rheumatology, COM and VAMC) Maria Gomes-Solecki (MIB, COM) Santosh Kumar (Pharmaceutical Sciences, COP) Vanessa Morales-Tirado (Ophthalmology, COM)

C. Equipment and research resources

FY18 equipment in the lab (all functional):

Equipment Cost Funding Source FACSAria II sorter $483,000 S10 RR022465 (PI: Marion), 2008 AMO aerosol maintenance incl with FACSAria Lauda recirculating bath incl with FACSAria Bio-Rad ZE5 $286,592* V-C Research 2016 *after discount and LSR II trade-in, List $355,342


BD Biosciences Aria II sorter $26,987

(Cytek Biosciences)

Bio-Rad ZE5 $29,695 (Bio-Rad)

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E. Usage Volumes

Service Types

FY17, volume

FY17, Hours

FY18, volume

FY18, hours

Flow cytometry

148 208.08 193 340.25

Cell sorting 26 55.80 31 63.50 Data

Analysis 5 7.97 46 66.50

Training 5 13.60 11 21.50 Total 184 275.45 279 491.75

F. Multi-year trends

UTHSC users

External or commercial users

Flow cytometry

Cell sorting

(# labs) (# labs) (total # uses) (total # uses) FY18 25 0 193 29 FY17 23 1 148 26 FY16 24 1 287 29 FY15 23 2 283 28 FY14 15 2 163 27 FY13 20 2 347 28 FY12 18 2 279 28 2011 25 2 318 37

G. Fee Structure

The fee structure outlined below is for FY18.

FACSAria (Cell Sorter) UTHSC External, Academic Commercial

2- or 4-way Sorting $123.00 $184.50 Negotiated agreement

Sorting to Plates or Single Cell Sorting $123.00 $184.50 Negotiated agreement

(Sorting charges, based on 1h min.+ 30 min of set-up.)

Bio-Rad ZE5 (Flow Cytometer) UTHSC External, Academic Commercial

Investigator-operated cytometry (billed in 30-minute increments) $52.00 78.00 N/A

Operator-assisted cytometry (billed in 30-minute increments) $72.00 $108.00 Negotiated

agreement

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Raw Data Analysis (30-minute minimum, then billed in 15 minute increments.

$52.00 $78.00 Negotiated agreement

Cytometry instrument and software training (per hour) $82.00 $123.00 N/A

IV. GRANTS THAT SUPPORT THE CORE

• Radic, Marko o Lupus Research Institute, CD19-Targeted Cytotoxic T Cells for Lupus

Therapy • Gosain, Ankush

o NIH DK098271, Gastrointestinal Mucosal Immune Defects in Hirschsprung’s Disease

• Gosain, Ankush o NIH DK114543, Validating Intestinal Enteroids to Study Hirschsprung's

Associated Enterocolitis • Gadiparthi, Rao

o NIH HL074860, Lipid Mediators and Vascular Diseases • Gadiparthi, Rao

o NIH HL103575, GPCR Signaling and Vascular Wall Remodeling • Jablonski, Monica

o William & Ella Owens Medical Research Foundation, Retinal Inflammasomes Mediate Ganglion Cell Death in Glaucoma

• Chauhan, Subhash o NIH CA 204552, MUC13 Mucin in Colorectal Cancer Health Disparity

• Chauhan, Subhash o NIH CA 206069, Development of Targeted Nanotechnology Platform for

Pancreatic Cancer • Li, Wei

o NIH CA148706, Targeting the Colchicine Site in Tubulin for Advanced Melanoma

• Li, Wei o NIH CA 193609, Selective Targeting Survivin for Cancer Therapy

• Miranda, Susan o NIH AR064354, Determining the Mechanism of How GATA4 Directs

ERalpha Binding in Osteoblasts • Miranda-Carboni, Gustavo

o Beckman Research Institute-City of Hope subcontract to U01 CA189283, Combined Breast MRI/Biomarker Strategies to Identify Aggressive Biology

• Jonsson, Colleen o NIH AI103053, Evolutionary Mechanisms of RNA Virus Host Switching

• Jonsson, Colleen o University of Louisville Subcontract to NSF 1516011, Collaborative

Research: Modeling Immune Dynamics of RNA Viruses in Reservoir and Nonreservoir Species

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• Huang, George o Lehigh University Subcontract to IIP-1602057, Preclinical Evaluation pf

Bioactive Tailored Amorphous Multiporous (Tamp) Powder for the Treatment of Dentin Hypersensitivity

• Gangaraju, Raja Shekhar o NIH EY023427, Vascular and Neuronal Repair with Adipose Stromal Cells

in Retinopathy • Zhang, Weiqiang

o NIH HL123535, Characterization of an Inhibitory Protein Complex for Cystic Fibrosis Therapy

• Reiner, Anton o NIH NS098137, Neural Control of Choroidal Blood Flow

• Hori, Roderick o NIH GM118962, The Role of UBTF in Undiagnosed Neurodevelopmental

Disorders V. BUSINESS DEVELOPMENT

A. FCCS Core history The UTHSC Flow Cytometry and Cell Sorting (FCCS) Laboratory was established in 2003. The mission of the Flow Cytometry and Cell Sorting Laboratory and the FCCS Core is to provide the UTHSC and Memphis Research Community with access to state-of-the-art instruments, expertise, and instruction and assistance with experimental design, and data analysis for digital, multicolor flow cytometry and cell sorting including indexed single-cell sorting. Prior to 2003, flow cytometry and cell sorting was part of the Molecular Resource Center (MRC). The acquisition of the BD Biosciences LSR II flow cytometer in 2003 with a shared equipment grant from NIH NCRR (PI: Tony Marion) provided UTHSC researchers with the first capability for the now standard digital "multicolor" flow cytometry. Flow cytometry was separated from the MRC at that time to become an independent research support laboratory. The core laboratory was expanded to include cell sorting in 2008 with the acquisition of the newly developed and state-of-the-art BD Biosciences FACSAria cell sorter also with NIH NCRR grant support (PI: Tony Marion). Dr. Marion initiated the movement to modernize flow cytometry and cell sorting at UTHSC, was PI for both instrumentation grants, and has been Director of the Core Laboratory since its inception. In 2016, the BD Biosciences LSR II flow cytometer was replaced with the Bio-Rad ZE5 21-color cytometer (formally known as the Propel Yeti). This ZE5 has provided the campus with a highly technically sophisticated flow cytometer with a yellow-green laser (561 nm), which the LSR II did not have. That deficiency had previously limited the usefulness of PE and PE-tandem fluorophores and the potential to incorporate red fluorescence proteins and "fruit dyes" into experiments that require those fluorophores, best, and in most cases only, excited by the 561 nm laser. The potential to quantify red fluorescence protein expression in single cells augments protocols that employ red fluorescence protein expression in in vivo imaging studies. In addition to the yellow-green laser with seven fluorescence detectors,

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the ZE5 has a violet, 405 nm; blue, 488 nm; and red, 640nm lasers with 7, 4, 7 and 3 fluorescence detectors for a total of 21 fluorescence detectors. The ZE5 also has a sensitivity FALS (forward angle light scatter) detector on the violet laser to improve detection of small, subcellular particles. In 2018, Dr. Deidre Daria replaced Dr. Terry-Ann Milford, Ph.D. as the full-time Flow cytometry Specialist to assist in the planning and execution of flow cytometry and cell sorting experiments.

B. Market Assessment

The FCCS Core provides access to state-of-the-art multicolor flow cytometry and fluorescence-activated cell sorting (FACS) for the UTHSC and Memphis research community. Services offered by the FCCS Core include training in the use of the flow cytometer as well as advice and assistance for multicolor flow cytometry experimental design and data analysis. The Core can also perform two- and four-way FACS and indexed single-cell FACS into microwells or onto microscope slides. These research services provided by the FCCS Core are competitive with similar flow cytometry and cell sorting research cores at other major research institutions. Pricing for services in the FCCS Core is likewise competitive with southeast regional research institutions. The FCCS Core has experienced relatively stable use of both flow cytometry and cell sorting services for the past five years (Section III.F). Over those five years, the FCCS Core has provided services for 15-25 individual research laboratories from thirteen total different departments, three Colleges and five outside academic institutions or commercial companies. Since the transition to the YETI (ZE5) flow cytometer, the core has doubled the number of trained users in FY18 when compared to FY17 and has seen an approximate 24% increase in the number of hours the ZE5 flow cytometer is in use. The FCCS Core is a critical resource for the grant-supported research mission at UTHSC as well as outsides researchers who depend upon the FCCS Core for critical data collection.

C. Competitive Analysis

There are other flow cytometers and cell sorters available in the Memphis medical center outside of UTHSC, housed within the LeBonheur Children’s Hospital, the Children’s Research Foundation, and the Memphis VA Medical Center, which include BD Biosciences LSR II and Accuri C6 flow cytometers, a Sony SH800 personal sorter, a Bio-Rad S3, and a FACSAria cell sorter. Users who choose these resources do so either because of convenience, or because they are free of charge (VAMC and Departmental “cores”). Although these other services do not advertise their services or actively compete with the FCCS Core, they do siphon away users who might otherwise use the FCCS Core.

D. Marketing Plans to Obtain New Business The capabilities of the FCCS Core, particularly in the area of single-cell analysis, need to be better communicated. The Operational Strategic Plan for Research (OSPR) has recognized the importance of including single-cell analyses into research protocols in all areas of research that involve analyses of cellular

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phenotypes and their manipulation, and the diversity of gene expression among individual cells with similar phenotype or origin. The FCCS Core has the capability to perform indexed single cell sorting based upon up to 12 different fluorescence parameters. The BD Biosciences LSR II flow cytometer was replaced in Q1 of FY17 with the Propel YETI (Bio-Rad ZE5) 21-color cytometer. As an early adopter, we had unlimited technical support and service from Propel. Bio-Rad acquired rights to manufacture and service the Yeti in 2017 as the ZE5. Bio-Rad also acquired rights to the Propel EVO software, now Everest, also in 2017.This ZE5 has provided the campus with a highly technically sophisticated flow cytometer with a yellow-green laser (561 nm), which the LSR II did not have. That deficiency had previously limited the usefulness of PE and PE-tandem fluorophores and the potential to incorporate red fluorescence proteins and "fruit dyes" into experiments that require those fluorophores, best, and in most cases only, excited by the 561 nm laser. In addition to the yellow-green laser with seven fluorescence detectors, the ZE5 has a violet, 405 nm; blue, 488 nm; and red, 640nm lasers with 7, 4, 7 and 3 fluorescence detectors for a total of 21 fluorescence detectors. The ZE5 also has a sensitivity FALS (forward angle light scatter) detector on the violet laser to improve detection of small, subcellular particles. Yellow-green laser excitation of several fluorophores will eliminate, or at least vastly reduce the problem of autofluorescence generated by the 488 nm laser. The potential to quantify red fluorescence protein expression in single cells will also augment protocols that employ red fluorescence protein expression in in vivo imaging studies. Workshops and/or “Hot Topics” dedicated to emphasizing the capabilities of the FCCS Core and how those capabilities can expand the research capabilities of research labs that utilize cell isolation and analysis need to be expanded in order to support the research mission at UTHSC and the viability of the FCCS Core. However, there have not yet been seminars dedicated to use of instrumentation in the core or workshops focused on flow cytometry techniques offered to the campus. To address this deficiency, Dr. Marion will take part in the Clinical Laboratory Sciences Lecture Series to discuss basic flow cytometry and its uses, which will by default highlight the FCCS core’s capabilities. Recruitment of a full-time Flow Cytometry Specialist, initially Terry-Ann Milford, Ph.D. and then Deidre Daria, Ph.D., has vastly improved the technical capabilities of the FCCS Core. Dr. Milford and Dr. Daria combined have more than 20 years of experience in flow cytometry, with extensive knowledge in planning and executing flow cytometry and cell sorting experiments.

E. Forecasted Volumes for New Business

With acquisition of the ZE5 flow cytometer in Q1 FY17, expectations were for increased use of the FCCS Core as newly recruited and existing researchers learn about the capabilities of the new instrument and how those capabilities can be incorporated into their research projects. At that time, we anticipated that it would

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take 1-2 years to transition users to the ZE5, to both allow for sufficient training and to make the campus aware of the unique features such as profiling of exosomes and small molecules offered by the ZE5 vs. the capabilities of previously used instruments (LSR II) or other instruments on campus. Because we have seen a steady increase in FY17 over FY18, we anticipate use of the core will continue to increase in FY19 over FY18. We will continue participating in events sponsored by SEFCIG to further expand our external customer base and we will participate in the Office of Research Hot Topics seminar series and recruit guest speakers for the cores’ special technology seminars that are focused on flow cytometry.

VI. Budget

Actual FY18 Budget: July 1, 2017 - June 30, 2018

FY2018 DEBITS CREDITS Salaries/Fringe Benefits* $94,381 Supplies $10,500 Service Contracts/Maintenance $61,213 Equipment (> $5,000) $0 TOTAL EXPENSES $166,094 FY18 Core Recoveries $28,892 Income (Subsidy) ($137,202)

*Dr. Tony Marion’s salary is entirely subsidized by the MIB. Due to a start date of April, 2018, the incoming Flow Cytometry Specialist salary (Deidre Daria) overlapped with the outgoing Flow Cytometry Specialist salary (Terry-Ann Milford) for two months. The salaries total also includes temporary consultant compensation for assisting with operation of flow sorting when Dr. Marion was unavailable. Subsidy: 82.6%, excluding Dr. Marion’s salary.

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Research Histology Core (RHC)

Research Histology Core (RHC) Institutional Research Core Facility Analysis Report- FY18 Written by Louisa Balazs, MD, PhD; Natalie Smith, MS; and Tiffany N. Seagroves, PhD 1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The RHC core designation as an institutional core is appropriate since it served 36 total unique users across multiple departments and Colleges. 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. In FY18, this core processed 98 sample submission requests for 36 unique users across ten departments and three Colleges (COM, COP, and CGHS). The departments with the largest number of users were the Department of Pediatrics (COM) with 12 users and the Department of Medicine (COM), with five users, respectively. The top five users, based on the percentage of collected revenues versus total core revenues, were Dr. Wei Li (Pharmaceutical Sciences, COP, 14%), Dr. Gustavo Miranda-Carboni (Medicine, COM, 10%), Dr. Tiffany Seagroves (Pathology, COM, 10%), Dr. Aristotelis Astreinidis (Pediatrics, COM, 9%) and Dr. Arnold Postlethwaite (Medicine, COM, 5%). The other 31 users accounted for the other 52% of core revenues. 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes, 36 unique users were served across multiple departments and Colleges. 4. Can the services for the core be outsourced more economically? No. The internal prices are very competitive relative to other similar academic cores (UTHSC is in the bottom quartile), or to commercial vendors. 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting? (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led two letters of support provided for grant applications. In addition, Dr. Balazs provided expert consultation on project design at no cost to the investigators. It is expected that future publications resulting from work performed in FY18 in the core will be reported in the FY19 core reports document. 6. Is the core currently self-sufficient or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution. After the State appropriation, the net subsidy was $56,621. Accomplishments this past year:

• The RHC was well-received in its inaugural year of operation as a partnership between the Office of Research and the Department of Pathology/University Clinical Health (UCH), supporting 36 users.

• The RHC designed and launched an iLab core facilities management module to support core service requests and invoicing, transitioning from paper forms.

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• UCH hired a full-time Pathology Manager, Ms. Deborah Wallin (a new position as of April 2018, which is fully funded by UCH). Ms. Wallin is the primary point of contact for investigators who submit samples to the core. Ms. Wallin has met with Dr. Balazs weekly to streamline core operations.


TOTALS FY17-18 Revenues 19,663 Expenses (94,718) Income (Subsidy) (75,055) Other Costs 0 Equipment 0 Net Income (Subsidy/Loss) (75,055) State Appropriation 18,434 Net Income (Subsidy/Loss) (56,621) Subsidy, % before State Appropriation

79%


59.7%

7. Suggested outcomes: It is recommended that RHC continue as an institutional core.

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Research Histology Core (RHC) Institutional Core Facility Summary of Institutional Core Activities for FY 2018 Written by Louisa Balazs, MD, PhD; Natalie Smith, MS; and Tiffany Seagroves, PhD I. PUBLICATIONS Full-length published articles (UTHSC faculty investigators are indicated in bold font, the Core Director is underlined)

No publications were generated from core activities as of June 30, 2018. Publications are expected in Year 2 of the core’s operation (FY19).

II. Conferences / Presentations

Dr. Balazs attended the Office of Academic, Faculty and Student Affairs faculty recognition event in the Spring of 2018.

III. PRESENTATIONS GIVEN TO PROMOTE CORE RESOURCES AND CORE USAGE

A. Tours Group tours are not provided since core activities are performed in an active clinical laboratory. Individual tours are arranged with Ms. Deborah Wallin at the request of investigators.

B. Courses and Internal Presentations

No courses or internal presentations were offered; advertising directly to departments is planned for FY19.

IV. SUMMARY OF ACTIVITIES A. Personnel

Directors: Louisa Balazs, M.D., Ph.D., Scientific Director (60% of university 0.75 FTE) and Abdallah Azous, M.D., Ph.D., Medical Director. Dr. Balazs consults with investigators about experimental design or evaluates the histopathology of completed research projects. Dr. Azous is the medical director for pathology services for University Clinical Health (UCH).

Laboratory Manager: Ms. Deborah Wallin. Ms. Wallin is a full-time employee of UCH and she was onboarded in April 2018. She is the direct contact for investigators to arrange core services. She is directly involved in processing research specimens and interacting with core customers during sample drop-off and pickup. Administrative Manager: Mr. Tim Hodge. Mr. Hodge supervises the personnel and the operating budget related to clinical pathology services for UCH. He is a full-time employee of UCH.

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Histotechnician: The equivalent of one half-time (50% effort) UCH employee is available to support research services for the RHC. Several histotechnicians rotate to complete research projects.

B. Oversight Committee

The following faculty were members of the FY18 Research Histology Core Internal Advisory Board (IAB):

Gustavo Miranda-Carboni (Medicine) Elena Parfenova (Physiology) RK Rao (Physiology) An IAB Chair has not yet been appointed. A Chair will be recommended in FY19 based on core usage in FY18.

C. Equipment and Service Contracts

All equipment that is maintained by the core is owned by UCH. Per the current contract agreement with UCH, UTHSC shares the costs of equipment maintenance agreements in a 50:50 split with UCH, after maintenance costs are first pro-rated for the fraction of completed research projects.

D. Usage Volumes by service request type

• Paraffin embedding of specimens only (without cut slides): 550 blocks • Sectioning of paraffin-embedded blocks: 3,091 slides • Paraffin embedding/1 cut slide/1 H&E: 664 specimens

Similar to a typical “clinical case” • H&E staining of previously cut slides: 138 stained slides • Non-H&E: special stains of cut slides: 129 stained slides • Frozen sections: 383 sections • Consultation hours (@$30/hr.): 6 hours

In addition to these fee-for-service options, the core trains researchers to properly employ histology and molecular pathology approaches and analysis protocols through consultation and training. The following services are provided at no charge: A) Consultation with investigators and their staff on proposed experimental design for histopathology during the design phase B) Seminars (Hot Topics) and workshops on campus in order to advertise the services offered by the core C) Boilerplate language for histology core facilities and resources for grant applications

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D) Letters of support, including estimated costs of core usage for grant submissions

Overall usage of the Core Lab: • The core processed 98 service requests for 36 independent investigators

across multiple Departments and three Colleges in FY18 (COM, COP, CHP).

UTHSC Departments that requested services FY18: College of Medicine: Pediatrics: 12 investigators Medicine: 5 investigators MIB: 4 investigators Pathology: 4 investigators Physiology: 3 investigators Pharmacology: 2 investigators Orthopaedic Surgery: 1 investigator Ophthalmology: 1 investigator Neurology: 1 investigator Other Colleges: Pharmaceutical Sciences (COP): 1 investigator Clinical Laboratory Services (CHP): 1 investigator

E. Multi-year trends (Bioinformatics)

FY18 was the first full year of service for the RHC Core, therefore, multi-year trend information is not relevant.

F. Fee Structure

The RHC core offers the following services, which are priced in the bottom-third to bottom-half tier relative to peer academic institutions that offer similar histopathology services. Paraffin Blocks and Slides: Processing without paraffin embedding: $2.50/cassette Processing and paraffin embedding: $3.00/block Unstained slides, paraffin block: $2.50/slide Recut of previously faced paraffin block: $2.50/slide H&E-staining of cut slides: $3.50/slide Frozen Embedded Sections: Unstained, cryosectioned slide: $5.00/slide* *cyrosectioning requests require an advance appointment H&E-staining of cryosectioned slide: $3.50/slide

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Special Stains: Please inquire -Special stain prices range from $15-$23/slide Extended consult with Scientific Director: $30.00/hour Applies to non-routine or special projects consultation, or for the evaluation of processed slides by the Core Scientific Director. Consultation related to experimental design should occur by appointment with the Core Scientific Director prior to sample submission and is available at no charge.

V. GRANTS THAT SUPPORTED THE CORE, FY18 • Gladysheva, Inna

o NIH HL115036, Corin in Cardiomyopathy and Heart Failure • Waters, Christopher

o NIH HL123540, CXCR4 Signaling in Lung Epithelial Repair • Li, Wei

o NIH CA148706, Targeting the Colchicine Site in Tubulin for Advanced Melanoma

• Quarles, Leigh o NIH AR045955, Regulation and Function of Fgf23

• Samarasinghe, Amali o NIH AI125481, Eosinophils as Regulators of Host Immunity Against

Influenza Infections • Waters, Christopher

o NIH HL131526, ASK1 and Ventilator-Induced Lung Injury • Yue, Junming

o American Heart Association15GRNT25000015, Role of miR27B in Vascular Wall Remodeling

• Seagroves, Tiffany o University of Minnesota Subcontract to NIH CA192178, Inducible PTK6

Expression Drives Oncogenic Signaling in Breast Cancer • Seagroves, Tiffany

o Department of Defense W81XWH-16-1-0061, Targeting Creatine Kinase, Brain Isoform (CKB) to Inhibit Metastatic Breast Cancer (MBC)

• Li, Wei o NIH CA193609, Selective Targeting Survivin for Cancer Therapy

• McDonald, Michael o NIH AG054562, Effects of Glycomacropeptide on Memory and Alzheimer-

Related Neuropathology • Park, Frank

o NIH DK090123, Ags3 In Ischemic Renal Injury

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• Tigyi, Gabor

o NIH AI107331, IND-Enabling Preclinical Development of a New Radiomitigator

• Bissler, John o Department of Defense W81XWH-14-1-0343, Prevention of TSC Renal

Disease

VI. BUSINESS DEVELOPMENT A. Market Assessment

The market for core services includes investigators who use research animals at UTHSC, LeBonheur and the surrounding Memphis area. Investigators who currently do not use the RHC either pay for their staff to prepare histology specimens, they use outside vendors such as LabCorp, or they use services offered by Methodist University Hospital pathology unit, which directly negotiates with investigators to provide research pathology services at a higher discount rate than the RHC institutional core.

B. Marketing Plans to Obtain New Business

The focus of marketing for the RHC core in FY19 will be to continue to expand the core customer base throughout Memphis and the UTHSC system. The core will continue to participate in events sponsored by the Office of Research, such as the Hot Topics, and the annual faculty fair/recognition event each Spring. The Scientific Director, Dr. Balazs, will also create the RHC core website. Dr. Balazs will also reach out to individual Departments to advertise RHC core services.

C. Forecasted Volumes for New Business

The core increased pricing for all services by 3% for the FY19 period. This new rate structure became effective July 1, 2018, which continues to place UTHSC in the bottom-half to bottom-third of peer academic institutions that offer histology services. Overall, it is expected the core volume will remain the same in FY20 as in FY19, unless newly recruited faculty begin to use the RHC core or the Methodist University Hospital pathology service unit redirects research projects from the hospital to the RHC for completion.

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VII. Actual Budget FY18 (July 1, 2017 to June 30, 2018)

FY2018 DEBITS CREDITS

Salaries $44,428 Supplies $50,290 Service Contracts $0 Equipment (> $5,000) $0 TOTAL EXPENSES $94,718 FY 18 Core Recoveries $19,663 FY18 State Appropriation $18,434 TOTAL CREDITS $38,097 Income / (Subsidy)** ($56,621)

Subsidy, before State appropriation, 79.2%

Subsidy, after State appropriation, 59.7%

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Medicinal Chemistry (MedChem)

Medicinal Chemistry Core (MedChem) Institutional Research Core Facility Analysis Report - FY18 Written by Jiawang Liu, PhD; Natalie Smith, MS; and Tiffany N. Seagroves, PhD 1. Relative to a specific core’s mission, is the designation as an “institutional core” appropriate? The MedChem core designation as an institutional core is appropriate since it served six investigators across multiple Departments and Colleges. The core also served one external investigator at the Louisiana State University Health Sciences Center (LSUHSC). 2. Does the Core pass the multi-departmental, multi-investigator litmus test? Yes. In FY18, this core processed custom synthesis projects and performed instrumental analysis services for six unique users across five departments and two Colleges (COM, and COP), and also served one external user. All six users are based in unique Departments. The top five users, based on the percentage of services fees invoiced, were Dr. Gabor Tigyi (COM, 67.2%), Dr. Glen Palmer (COP, 15.8%), Dr. Yaguang Xi (external, 12.7%), Dr. Qi Zhao (COM, 2.3%) and Dr. Ying Kong (COM, 0.9%). The remaining user, Dr. Madhura Hallman (LeBonheur) accounted for the other 0.9% of core activity. 3. Is there sufficient intra- and inter-departmental use and if not, why? Yes. Six unique users were served across multiple departments, Colleges, including one external, out-of-state user. 4. Can the services for the core be outsourced more economically? No. 5. Are there unaccounted benefits beyond fiscal consideration to warrant continued institutional underwriting? (e.g. grants funded through investigator use, publications, etc.)? Yes. In FY18, core activities led to nine letters of support on grant applications, and two pending grant applications that included Dr. Liu as a paid co-PI. In addition, Dr. Liu provided two internal workshops and seminars on campus related to drug discovery and design that were well-attended. 6. Is the core currently self-sufficient or is it subsidized by the Institution? In FY18, the core was subsidized by the Institution. Overall, FY18 ended with a net subsidy of $163,643 (92.2%), which includes support from the VC for Research fund. Accomplishments this past year: The MedChem core was well-received in its first, partial year of operation as the inaugural institutional medicinal chemistry core on the UTHSC campus. The core signed a contract for future services with a local biotech company, RxBio.

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Financial overview, FY18:

TOTALS FY18 Revenues 13,833 Expenses (12,725) Income (Subsidy) 1,108 Other Costs* (80,000) Equipment** (84,752) Net Income (Subsidy/Loss) (163,643) Subsidy, % 92.2%

*Dr. Liu’s salary was funded by the VC for Research. **All equipment and computer expenses necessary to launch the MedChem core were funded by the VC for Research. The total subsidy, including support from the VC for Research, is 92.2%.

7. Suggested outcomes: It is recommended that MedChem continue as an institutional core.

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Medicinal Chemistry (MedChem) Institutional Core Facility Summary of Institutional Core Activities for FY18 Written by Jiawang Liu, PhD; Natalie Smith, MS; and Tiffany Seagroves, PhD

I. PUBLICATIONS (Journal publication dates: July 1, 2017 to June 30, 2018)Full-length published articles (UTHSC faculty investigators are indicated in boldfont, Director underlined)

None

II. PRESENTATIONS GIVEN TO PROMOTE CORE RESOURCES AND CORE USAGEA. Internal Presentations

1. 08/28/17: the Director presented a special seminar sponsored by the Officeof Research as an update to the Medicinal Chemistry working group to highlight“Services Provided by the Medicinal Chemistry Core”2. 02/28/18: the Director presented at a UTHSC Drug Discovery AdvisoryGroup Meeting, “MedChem Core: A Half-Year Progress Report.”

III. SUMMARY OF ACTIVITIESA. Personnel

Director: Jiawang Liu, Ph.D., 100% effort

B. Oversight CommitteeThe following faculty were members of the FY18 Medicinal Chemistry InternalAdvisory Board (IAB):

Subhash Chauhan, PhD (Pharmaceutical Sciences. COP)Wei Li, PhD (Pharmaceutical Sciences, COP)Len Lothstein, PhD (Pathology, COM)Bernd Meibohm, PhD (Pharmaceutical Sciences, COP)Duane Miller PhD (Pharmaceutical Sciences, COP)Ramesh Narayanan, PhD (Pathology, COM)Gabor Tigyi, PhD (Physiology), IAB Chair

C. EquipmentEquipment currently maintained in the core facility (all functional):

Equipment: Cost: Funding Source: Purchase Date:

Flash column system $52,857 Office of Research 10/01/2017

Microwave Reactor $19,967 Office of Research 10/01/2017

Rotation Evaporator $12,000 On loan by RxBio Not Applicable

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D. Service ContractsNo service contracts were purchased in FY18 for equipment maintenance.

E. Usage Volumes, FY18

By PI Name (Department):

Total Service Fees, FY18:

Percentage of Usage, FY18:

Kong, Ying (MIB)

$160.00 0.9%

Palmer, Glen (Clinical Pharmacy)

$2,580.00 15.8%

Tigyi, Gabor (Physiology)

$10,940.00 67.2%

Xi, Yaguang (LSUHSC, external) †

$2,065.50 12.7%

Zhao, Qi (Preventive Medicine)†

$380.00 2.3%

Hallman, Madhura (LeBonheur)

$152.52 0.9%

TOTAL INVOICED, FY18

$16,278.02 100.0%

TOTAL RECEIVABLES, FY18‡

$13,832.12

†Services were invoiced in FY18, but payment was not received until FY19

F. Multi-year trends

FY18 was the first year of offering services for the MedChem Core. The core wasestablished in the Fall of 2017 and officially began to provide services to campusinvestigators on Jan 1st, 2018. Therefore, the core received revenues only duringQ3-Q4 of FY18.

Custom Synthesis Projects:

Year Total Invoiced

FY18 $15,738.02

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Year Total Invoiced

FY18 $160.00

Chemical Ordering on Behalf of Customers:

Year Total Invoiced

FY18 $380.00

**Note: $2,445.90 in fees for services were invoiced in FY18, but funds were not received until FY19.

G. Fee StructureIn FY18, during its first year of operation, fees for services were developed bythe Director based on a market-based comparison of peer academic institutionsand recommended to be in the bottom-half to the bottom-third tier relative to peeracademic institutions. Prices were approved by the core Internal Advisory Board(IAB) and the Vice Chancellor for Research.

i.) Core Support Services

Service Code Service Description Price, $ P010 Support letter No charge P020 Experimental design/outline No charge P030 Chemical structure figure

and synthetic route scheme No charge

P040 3D Protein and ligand images

No charge

ii.) Research Strategy Assistance

Service Code Service Description Price, $ R010 Literature search for

compounds No charge

R020 Literature search for targets or pathways

No charge

R030 Oral literature search report No charge R040 Well-written, literature

search report provided in Word (Font: Arial; 12; Page size; Letter)

$50/page

R050 Synthetic route design $20/reaction

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Instrumental Analysis:


R060 Drug screening method determination

$100/method

Iii.) Small Molecule Synthesis

Service Code Service Description Price, $ S010 Reaction (10 – 500 mg) $30/hour * S014 Reaction (0.5 – 1.0 gram) $30/hour * S020 General workup (10 – 500

mg) $120/step

S024 General workup (0.5 – 1.0 gram)

$200/step

S030 Column chromatography (10 – 500 mg)

$120/step

S034 Column chromatography (0.5 – 1.0 gram)

$200/step

* The maximum charge for a reaction is $240 (8 hours).

iv.) Instrumental Analysis services:

Service Code Service Description Price, $ S040 1H and 13C NMR $40/sample S050 MS (ESI) or LC/MS $40/sample S055 HPMS $40/sample S060 Melting point No Charge S070 Specific rotation No Charge

Service fee calculation examples: A typical 5-step synthesis project (0.5-1 gram): [$30/hour x 6 hours (mean reaction time for one reaction) + $200/step x 2 steps + $40/analytical assay x 2 assays = $660/step] x 5 steps =$3,300 + costs of starting materials and special reagents

A typical 5-step synthesis project (20-50 mg): [$30/hour x 6 hours (mean reaction time for one reaction) + $120/step x 2 steps + $40/analytical assay x 2 assays = $500/step] x 5 steps =$2,500 + costs of starting materials and special reagents.

Note: The example service fee for a 5-step synthesis protocol does not include the costs of starting materials, anhydrous solvents, or any special reagents. Users must pay for these costs before synthesis services are initiated. A list of common solvents and regular reagents that are included in service fees is provided to core customers prior to initiation of services.

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Service Code Service Description Price, $ W010 Write-up for publication(s),

including supporting information (Times New Roman, 11; Double spacing; Letter)

$100/page

W020 Compound identity and purity report

No charge

W030 NMR and MS spectrum copy No charge

vi.) Chemical Mailing and Processing Services

Service Code Service Description Price, $ M010 Product handling and delivery

fee No charge (internal) $50 (domestic) $200 (intl.)

M020 Starting material quotation No charge M030 Chemical storage and

processing No charge

In addition to these fee-for-service options, the following services are provided to UTHSC investigators at no charge:

1) Face-to-face consultation with investigators on their grant applicationand proposed experimental design.

2) Seminars and workshops provided to campus in order to advertisethe services and expertise offered by the core.

IV. GRANTS THAT SUPPORT THE CORE, FY18Pending• Qi Zhao, MD, PhD (Preventive Medicine, COM), NIH, “Longitudinal Prenatal

Metabolomic Profiling for Predicting Early Childhood Growth and Overweight/Obesity Risk”.

• Darryl Quarles, MD, PhD (Medicine, COM), NIH/NIDDK, “Optimization ofNovel Small Molecules to Antagonize FGF-23”.

Nine letters of support were also written in support of grant applications on behalf of six independent investigators.

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v.) Write-ups for Reports, Publications, and other Purposes


A. Market AssessmentIn August 2017, members of the drug discovery and drug development sub-committee of the OSPR committee drafted an online survey related to drugdiscovery and drug development needs at UTHSC, which was distributed by theOffice of Research. Over 100 respondents completed the survey. Approximatelyhalf of respondents were currently engaged in drug discovery research (52/102),and 43 respondents planned to begin research in this area within the next twoyears (43/80 respondents who replied to this question). Approximately 30respondents were interested in applying for SBIR/SSTR grants to support theirdrug discovery and development projects. The primary research interests offaculty who responded to the survey were focused around drug formulation, leadoptimization, off-label use of existing drugs, and drug target identification.

To further refine the interest in drug discovery and drug development services, aMedical Chemistry Core user interest meeting was held on August 28th, 2017,which was led by Drs. Gabor Tigyi and Jiawang Liu. Contact data for theinvestigators who attended, and who were interested in forming a working groupin this area, were collected. The core facility then began offering consultationswith investigators prior to installation of the equipment necessary to begin drugsynthesis.

The core is defined as an institutional core based on its potential to serve facultyin multiple Colleges and Departments within UTHSC, with initial interest inservices from four primary Colleges, including College of Medicine, College ofPharmacy, College of Nursing, and College of Dentistry. The potential customersfor our base include UTHSC, other UT campuses, the University of Memphis, theVA, Le Bonheur Hospital, and other commercial and academic partners in theMemphis metropolitan area. Based on Dr. Liu’s prior success at Xavier Universitydirecting a similar core, it is also likely that other external users will also use ourcore at UTHSC.

B. Competitive AnalysisThe Medicinal Chemistry Core is essential to the campus to support drugdiscovery efforts and all basic, pre-clinical, clinical and translational research thatimpacts human disease and treatment. It is also critical for the successful hiringof faculty interested in Precision Medicine and Translational Medicine. TheMedChem core will offer value-added services that include the scientific expertiseand breadth of training of the Director, quick turnaround time, and state of the artinstrumentation that most core facilities in the United States have not yet adopted.The Medicinal Chemistry Core is also a highly desired campus resource of severalnewly recruited faculty, or faculty who have recently interviewed for key positionson our campus, including Institute Directors and Department Chairs, such as theDirector for Research for the West Cancer Center, and the new Chair of theDepartment of Physiology.

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V. BUSINESS DEVELOPMENT


C. Marketing Plans to Obtain New BusinessA primary focus of the Medicinal Chemistry Core in FY19 will be to expandadvertisement of core services to the UTHSC campus, throughout the MemphisMedical Center and throughout the University of Tennessee system. The brandingstrategy will involve enhanced local advertisement on the campus, participationin the Hot Topics in Research seminar series, participation in Office of Researchsponsored institutional “Core Days” and in institutional “Core Success” seminars.These activities will be supported by development of a new core website by theOffice of Research and development of new print materials, including acomprehensive Institutional Core brochure and specific Medicinal Chemistry Coreprint advertisements to be posted around campus. In addition, the Core will hostOpen Houses for potential users to tour the facility and meet new core staff, andthe Director will develop workshops for the UTHSC campus that are focused ondrug discovery and development.

In the “Core Success” seminars, users who are highly satisfied with the coreservices will showcase their latest research successes. The envisioned format isthat 2-3 investigators will present data and the outcomes of their projects thatrelied on the core services to the research community. In addition, presenters willbe encouraged to identify roadblocks that were overcome by interactions with theCore Director, which will increase awareness of value-added services. IABmembers have also committed to actively using and advertising the core services.By focusing on core outcomes rather than just advertising ourtechnology/facility/resource capabilities, we will leverage the satisfaction of ourcore users to assist us in advertising the core as a reliable, value-added fee-for-service core.

To maintain expertise and to remain current in evolving medicinal chemistrytechnologies, the Director will attend regional and national meetings, such asconferences sponsored by the American Chemical Society (ACS) and AmericanAssociation for Cancer Research (AACR). Attendance of those meetings will alsobe a venue for advertisement of the medicinal chemistry core at theregional/national level since the core facility will be advertised in all posters or oralpresentations made by the Director.

D. Forecasted Volumes for New BusinessGiven that the core is new to campus and was functional to complete projects foronly one half of FY18, it is difficult to estimate FY19 revenues. We estimate thatrevenues will double in FY19, if demand for services remains the same asobserved during FY18.

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FY2018 DEBITS CREDITS Salaries/Benefits* $80,000 Supplies $12,725 Service Contracts $0 Equipment (> $5,000)* $84,752 TOTAL EXPENSES $177,477 FY18 CORE RECOVERIES $13,833 Income (Subsidy) ($163,643)

*Staff salary and all equipment purchases to launch the core were funded bythe VC for Research.

Subsidy: 92.2%, including the staff salary and equipment provided by the VC for Research.

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VI. FY18 Actual Budget (from September 1, 2017 to June 30, 2018)

Conclusions and Global Recommendations Impacting All Cores Strong support of research cores and shared facilities is essential to maintaining international recognition of research programs, increasing extramural funding and recruiting and retaining outstanding research faculty. Institutional cores are defined as shared resources that are, or will be, widely used among UTHSC faculty from multiple Departments, Colleges and, in the future, Campuses. The Institutional Research Cores currently receive their budget from the State of Tennessee and the Institution, which then receives all fees for service. The fees are set based upon market evaluation. Since FY16, institutional cores are now expected to sit on their financial bottom, to be managed with a business model using business plans to develop budgets and to employ data-based metrics to measure core success. As noted in the sections of the report devoted to individual cores, a number of operating and financial accomplishments were made over the past fiscal year as a result of adoption of the new business plan model to manage core facility operations launched in FY16. The cores increased their promotional efforts through more frequent presentations to individual Departments, through the Office of Research Hot Topics seminar series and through invitation of special guest speakers sponsored by the cores focused on emerging technologies. The cores also revised their websites and developed new marketing materials, such as the one-page core brochures and color printed core booklets, which are distributed in print at the Office of Academic, Faculty and Student Affairs faculty fair and recognition event held each Spring. Additionally, several investments were made in FY18 using the Vice Chancellor for Research funds to support the cores, including the Core Director salary and all necessary equipment to launch the MedChem core ($164,751), and 50% of the new and replacement animal caging for the LACU ($275,476). Overall, since FY16, ~$2.5M of the $5M in funds distributed to the VC for Research startup fund have been used to subsidize core facilities. Although rates for core services were increased by 3% over FY17 levels, these increases were insufficient to offset the decreased revenues attributed to decreased per diem and service fee revenues for the LACU and the RBL. For example, several multi-award investigators using rodents left UTHSC in FY18, leading to decreased per diem and service fee revenues and there were no external users of the RBL in FY18. Cores with increased revenues in FY18 as compared to FY17 included the MRC, FCCS and PMC Cores. Revenues for the mBIO Core remained stable in FY18 relative to FY17. Overall, the net result is that, after accounting for subsidies (“income”) from the State of Tennessee, THEC and the VC for Research startup funds for the cores’ operating budgets, the total subsidy for all UTHSC institutional cores in FY18 was $2,131,536, an increase of $1,624,312 compared to FY17. Through the actions implemented since the initial core business plans were developed in March 2016, the Office of Research has built the foundation to make the institutional cores

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stronger and more streamlined in the future. There has been significant progress made in core operations in FY18, including increased staffing and implementation of quality control/quality assurance protocols in the LACU and RBL, development of new cores (MedChem, RHC) and new core service offerings (RBL and MPMS Unit of the PMC) as well as necessary core renovations and core equipment upgrades. These improvements required additional investment/subsidy relative to FY17. There remain opportunities for further improvements in managing core operations, including vigorous marketing to increased demand for core services, leading to increasing core revenues, increasing State of Tennessee and/or institutional subsidies, and aggressively managing core operational costs to achieve our long-term goal to reduce overall core subsidies while investing in launching one new institutional core per fiscal year, as outlined in the Operational Strategic Plan for Research (OSPR). In FY18, two new Institutional Cores were opened, the Medicinal Chemistry (MedChem) and the Research Histology Core (RHC), and the Metabolic Phenotyping Mass Spectrometry (MPMS) Unit was added to the PMC. In addition, as part of planning for a new Advanced Animal Imaging (AAI) core to address small animal imaging needs, a light sheet fluorescent microscope (LSFM) system was purchased by the VC for Research in FY18 (Dr. WenLin Sun, Director) for accepting specimens in FY19 and a rodent MRI imaging system managed under the AAI Core is planned for a FY20-FY21 launch. The business plan for an additional institutional core, the STATistics and Experimental Design (STATED) core, was approved by Research Council, but was not funded in FY18. Across the board, the specific recommendations for all institutional cores are outlined below:

• All Institutional Cores should continue to incorporate an annual inflationary increase of 3% in user fees to match the 3% inflationary increase that can be requested on NIH grants and other extramural funding sources.

• Continue to promote core capabilities and expertise to internal users, and to expand marketing of core capacities to external users, including commercial users who would pay higher service fees. The cores will also continue to participate in additional faculty fair events sponsored by the Office of Academic, Faculty and Student Affairs in Spring each year.

• To strive to eliminate redundant, underutilized core resources or to outsource commodity services in order to invest in emerging technologies in the core facilities.

• To develop and to invest in new Institutional Core Facilities in congruence with the Operational Strategic Plan for Research (OSPR) to develop new core facilities that support the research strengths of UTHSC. For FY19-21, these new Institutional Cores will include the Advanced Animal Imaging (AAI) core and the STATED core.

• Continue to support the integration of the iLab core facility management solution software on campus so that a unified system for requesting core services and for managing core invoicing and reporting becomes streamlined. At the close of FY19, core metrics for the MRC, FCCS, PMC, RHC, mBIO, MedChem and AAI cores will be readily downloadable direct from iLab. Data for RBL services, but not for rodent per diems, will also be available through iLab.

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• Continue to support distribution of boilerplate language for grant and contracts related to institutional core resources and facilities and update these documents at least bi-annually.

• Survey core users more frequently to receive up-to-date feedback about the quality of core services, the perceived value of core services, turnaround time for sample processing and customer service quality, in order to further improve core operations.

• When feasible, work with Colleges to eliminate redundant purchases of equipment for faculty recruitment that already exists in Institutional Cores and/or may compete with the Institutional Cores.

• When feasible, work with Centers and Institutes to cost-share core capital equipment to be utilized by a broad group of member investigators, such as a rodent MRI system.

• Continue to work with the Office of Development and Alumni Affairs to develop relationships with new philanthropic sources, and to build relationships with equipment vendors, who may provide discounted or gift-in-kind equipment for the cores. As part of this ongoing effort, Greg Harris became a member of the VCR Research Cabinet in FY18.

• If investigators are using uncompensated time of core directors and/or personnel, then it is fair and reasonable that they should be added on the faculty member’s grant application for the percentage of time utilized. We will continue to engage with the Associate Vice Chancellor for Research-Office of Sponsored Programs (Sarah White, MA, Ed.M) to ensure these guidelines are enforced during pre- and post-award review.

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