CURRICULUM VITAE Personal Information: Name: Silva Markovic ...

CURRICULUM VITAE Personal Information: Name: Silva Markovic-Plese Education: Ph.D. University of Zagreb, Neurobiology Postgraduate Studies, 2011 Zagreb, Croatia Research Associate Neuroimmunology Branch of National Institute of Neurological

Diseases and Stroke, National Institutes of Health, Bethesda, MD 1998-2001

Neurology Resident Yale New Haven Hospital, Yale University School of 1995-1998

Medicine, New Haven, CT

Medical Intern Hospital of St Raphael, Yale University School of Medicine, 1994-1995 New Haven, CT

Postdoctoral Fellow Center for Neurological Diseases, Brigham and Women's 1991-1994 Hospital, Harvard Medical School, Boston, MA

M.S. University of Zagreb, Neurobiology Postgraduate Studies, 1989-1991 Zagreb, Croatia Clinical Fellow Department of Neurology, University Hospital Rebro, Zagreb 1989-1991

Croatia

Medical Intern Vrapce Hospital for Psychiatric Diseases, Zagreb, Croatia 1988-1989

M.D. University of Zagreb Medical School, Zagreb, Croatia 1982-1988 Professional Experience—Employment History: Associate Professor of Neurology, Immunology and Microbiology with permanent tenure, University of North Carolina at Chapel Hill, Chapel Hill, NC 5/2008-present Associate Professor of Immunology and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 9/2004-present

Associate Professor of Neurology, Chief, Neuroimmunology Division, Director of Multiple Sclerosis Clinic, University of North Carolina at Chapel Hill, Chapel Hill, NC 8/2003-present Assistant Professor of Neurology Yale University School of Medicine, New Haven, CT, 7/2001-7/2003

Markovic-Plese, M.D.

Instructor in Neurology Department of Neurology, Yale University School of Medicine, New Haven, CT 7/1997-7/1998 Awards and Honors: Co-chair, oral presentation session, Multiple Sclerosis, Novel Mechanisms of Action, 2013 AAN Annual Meeting, San Diego Reviewer for MS and Related Diseases abstracts for the 2013 AAN Annual Meeting, San Diego 2013 Co-chair, oral presentation session, 6th Dubrovnik International Conference on Multiple Sclerosis, Dubrovnik, Croatia 2012 5th Dubrovnik International Conference on Multiple Sclerosis, Program Organizing Committee, Co-chair, oral presentation session, Dubrovnik, Croatia 2009 National Multiple Sclerosis Society, Eastern North Carolina Chapter, Distinguished Clinician Award 2007 UNC MS Center Director, UNC MS Center Affiliated with National MS Society 2005 Member of Clinical Advisory Committee, Eastern North Carolina Chapter, National Multiple Sclerosis Society 2003-present Career Development Award, The Mechanisms of Autoimmune Response Initiation in Multiple Sclerosis, NIH, NINDS, 2003-2008 Co-chair, oral presentation session, Multiple Sclerosis: Clinical Immunology, American Academy of Neurology, Honolulu HI 2002 Co-chair, oral presentation session, Multiple Sclerosis: Animal Models, American Academy of Neurology, Denver, CO 2001 Fellows Award for Research Excellence 2000, National Institutes of Health 2000 Neuroimmunology Fellowship, Neuroimmunology Branch, NIH, NINDS 1998-2001 Memberships: Active Member American Academy of Neurology 2001-present Trainee Member American Academy of Neurology 1993-2001 Member American Association of Immunologists 1999-present Board Certification: 2011 Neurology and Psychiatry Maintenance of Board Certification 2000 Neurology and Psychiatry


Bibliography:

Book Chapters: Montes, M., Jin, J.P., Markovic-Plese, S: Characterization of Cellular Infiltrates from MS Lesions in Various Stages of Development, In: Current Topics in Neuroimmunology, Eds. Tabira, Yamamura, Kira, Medimond, 59-64, 2006 Markovic-Plese, S., Gaylord, S., Mann, D.J.: Chapter 101. Multiple Sclerosis. In: Netters Internal Medicine. Second Edition. Marschall S. Runge and M. Andrew Greganti, Eds. Icon Learning Systems, Teterboro, NJ. 2006.

Referred article: Original research:

Sha, Y., Troiani, L., Chopra, M., Markovic-Plese, S.: Activated IL-1RI Signaling Pathway Induces Th17 Cell Differentiation in Patients with Multiple Sclerosis of IRF4 signaling cascade, J. Immunol, In Submission, 2013 Blauth, K., Zhang, X., Chopra, M., Troiani, L., Markovic-Plese, S.: Fractalkine upregulates ICAM-1 selectively in CD4+ T lymphocytes: implications for multiple sclerosis, J. Autoimm, In Submission, 2013

Tao, Y., Zhang, X., Chopra, M., Troiani, L., Kim, M., Jin, J., Tang, Y., Jewells, V., Markovic-Plese, S.: Decreased endogenous IFN� secretion contributes to the Th17-cell-mediated autoimmune response in patients with relapsing-remitting MS, In Submission, Neurology, 2013 Zhang, X., Tao, Y., Chopra, M., Troiani, L., Marcus, K., Choudhary, N., Krolczyk, S., Wray, S., Markovic-Plese, S.: Immunological Reconstitution Following Alemtuzumab (�CD52 mAb) Treatment in Patients with Relapsing Remitting Multiple Sclerosis, In Revision, Science Translational Medicine, 2013 Zhang, X., Tao, Y., Jin, J., Tang, Y., Markovic-Plese, S.: IL-11-producing CD4+ T-cells induce Th17-cell differentiation and expansion in patients with first clinical presentation of multiple sclerosis, In Revision, Journal of Clinical Investigations, 2013

Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators (Markovic-Plese, S): Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Zhang, X., Tao, Y., Wang, J., Garcia-Mata, R., Markovic-Plese, S.: Simvastatin Inhibits Dendritic Cells’ Th17-polarizing Cytokine Secretion and Antigen Presentation in Patients with Relapsing Remitting Multiple Sclerosis, Eur. J. Immunol, 2013, 43(1):281-9


Li, Y., Jewells, C., Kim, M., Chen, Y., Moon, A., Armao, D., Troiani, L., Markovic-Plese, S., Lin, W., Shen, D.: Diffusion Tensor Imaging Based Network Analysis Detects Alterations in Neuroconnectivity in Patients with Relapsing Remitting Multiple Sclerosis, Brain Mapping, 2012, doi: 10.1002/hbm.22158 Brück, W., Popescu, B., Lucchinetti, C.F., Markovic-Plese, S., Gold, R., Thal, D.R., Metz, I.: Neuromyelitis Optica Lesions May Inform Multiple Sclerosis Heterogeneity Debate, Ann Neurol, 2012 Sep;72(3):385-94. doi: 10.1002/ana.23621. Broux, B., Pannemans, K., Zhang, X., Markovic-Plese, S., Broekmans, T., Eijnde, B.O., Van Wijmeersch, B., Somers, V., Geusens, P., van der Pol, S., van Horssen, J., Stinissen, P., Hellings, N.: CX(3)CR1 drives cytotoxic CD4(+)CD28(-) T cells into the brain of multiple sclerosis patients. J Autoimmun, 38(1):10-19, 2012

Zhang, X., Tao, Y., Wang, J, Luigi Troiani,, L., Garcia-Mata, S., Markovic-Plese, S: Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell differentiation in CD4+ T cells derived from patients with multiple sclerosis, J Immunol, 187(6):3431-3437, 2011

Meeker, R.B., Poulton, W., Markovic-Plese, S., C, Hall, K. Robertson: Protein changes in CSF of HIV-infected patients: evidence for loss of neuroprotection. Journal of Neurovirology, 17(3):258-73, 2011. Ramgolam, V., Sha, Y., Marcus, K.L., Choudhary, N., Troiani, L., Chopra, M. Markovic-Plese, S: B cells as a Therapeutic target for IFNb-1b in Relapsing-Remitting MS, J Immunol, 186(7):4518-26, 2011 Ramgolam VS, DeGregorio SD, Rao GK, Collinge M, Subaran SS, Markovic-Plese S, Pardi R, Bender JR.: T cell LFA-1 engagement induces HuR-dependent cytokine mRNA stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 signaling cascade., PLoS One. 2010 Dec 29;5(12):e14450. Ramgolam, V., Sha, Y., Jin, J., Zhang, X., Markovic-Plese, S.: Interferon-beta Inhibits Human Th17 Cell Differentiation, J Immunol, 15;183(8): 5418-5427, 2009 Buie, L.K., Rasmussen, C.A., Porterfield, E.C., Ramgolam, V., Makovic-Plese, S., Chon, V.W., Samulski, R.J., Kaufman, P.L., Borras, T.: Self-complementary AAV Virus (scAAV) Override AAV Transduction Inability and Confer Long-term Expression to the Trabecular Meshwork of Living Animals, Investigative ophthalmology and visual sciences, [Epub ahead of print], 2009 Markovic-Plese, S., Jewells, V., Speer, D.: Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis, Neurology, 72(22):1965-1966, 2009

Cohen, J.A., Imrey, P.B., Calabresi, P.A., Edwards, K.R., Eickenhorst, T., Felton, W.L. 3rd, Fisher, E., Fox, R.J., Goodman, A.D., Hara-Cleaver, C., Hutton, G.J., Mandell, B.F., Scott, T.F., Zhang, H., Apperson-Hansen, C., Beck, G.J., Houghtaling, P.L., Karafa, M.T., Stadtler, M., ACT Investigators (Markovic-Plese, S.): Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS, Neurology, 72(6): 535-41, 2009


Zhang, X., Jin, J., Tang, Y., Speer, D., Sujkowska, D., Markovic-Plese, S.: IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation, J Immunol, 182(6):3928-3936, 2009

Montes, M., Zhang, X., Berthelot, L., Laplaud, D.A., Brouard, D., Jin, J., Armao, D., Jewells, V., Soulillou, J.P., Markovic-Plese, S.: Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells, Clin Immunol, 130(2): 133-144, 2009

Zhang, X., Jin, J., Tang, Y., Ramgolam, V., Markovic-Plese, S.: Simvastatin Inhibits IL-17 Secretion by Targeting Multiple IL-17-regulatory Cytokines and by Inhibiting the Expression of IL-17 Transcription Factor RORC in CD4+ Lymphocytes. J Immunol. 2008,180(10):6988-6996. Zhang, X., Tang, Y., Danuta, S., Wang, J., Ramgolam, V., Sospedra, M., Adams, J., Martin, R., Pinilla, C., Markovic-Plese, S.: Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis. Eur J Immunol. 2008 May;38(5):1297-1309. Cohen, J.A., Calabresi, P.A., Chakraborty, S., Edwards, K.R., Eickenhorst, T., Felton, W.L. 3rd, Fisher, E., Fox, R.J., Goodman, A.D., Hara-Cleaver, C., Hutton, G.J., Imrey, P.B., Ivancic, D.M., Mandell, B.F., Perryman, J.E., Scott, T.F., Skaramagas, T.T., Zhang, H.; ACT Investigators (including Markovic-Plese, S.): Avonex Combination Trial in relapsing--remitting MS: rationale, design and baseline data. Mult Scler. 2008 Apr;14(3):370-82. Kasper, L.H., Everitt, D., Leist, T.P., Ryan, K.A., Mascelli, M.A., Johnson, K., Rayehaudhri, A., Vollmer, T. Markovic-Plese, S. The Multiple Sclerosis Investigators. A phase I trial of an Interleukin-12/23 monoclonal antibody in relapsing remitting multiple sclerosis. Curr Med Res Opin, 2006: 22(9): 1671-1678, Erratum published in Curr Med Res Opin. Nov 2007 Tyor, W.R., Singh, I., Vollmer, T.L., Key, L., Corboy, L., Markovic-Plese, S., Preningerova, J., Durkalski, V., Rizzo, M.: The Use of Statins in Multiple Sclerosis, Int MS Care, 8:10-12, 2006 Peng, X., Jin, J, Giri, S., Montes, M, Sujkowski D, Tang Y, Smrtka, J, Vollmer, T.L., Singh, I., Markovic-Plese, S: Immunomodulatory Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme-A Reductase Inhibitors, Potential Therapy for Relapsing Remitting Multiple Sclerosis, J Neuroimmunol, 178:130-139, 2006 Markovic-Plese, S., Hemmer, B., Pinilla, Zhao, Y., Martin R. High Level of Cross-Reactivity in Influenza Virus Hemagglutinin-Specific CD4+T Cell Response: Implications for the Initiation of Autoimmune Response in Multiple Sclerosis, J Neuroimmunol, 169: 31-38, 2005 Lindzen, E., Gilani, A., Markovic-Plese, S., Mann, D. Acute Disseminated Encephalomyelitis Following Liver Transplant, Arch Neurol, 62(4):650-652, 2005


Bielekova, B., Richert, N., Howard, T., Blevins, G., Markovic-Plese, S., McCartin, J., Wurfel, J., Ohayon, J., Waldman, T.A., McFarland, H., Martin, R. Humanized Anti-CD25 (Daclizumab) Inhibits Disease Activity in Multiple Sclerosis Patients Failing to Respond to Interferon-Beta, PNAS, 101(23):8705-8708, 2004 Vollmer, T., Key, L., Durkalski, V., Tyor, W., Corboy J., Markovic-Plese, S., Preningerova J., Rizzo, M., Singh, I. High Dose Oral Simvastatin Therapy in Relapsing-Remitting Multiple Sclerosis: An MRI Study, Lancet, 363:1067-1068, 2004 Markovic-Plese, S., Bielekova, B., Kadom, N., Leist, T., Martin, R., Frank, J., McFarland, H.F. Longitudinal Magnetic Resonance Imaging Study: The Effects of Azathioprine in Multiple Sclerosis Patients Refractory to Interferon β-1b, Neurology, 10:60(11): 1849-51, 2003 Taylor, P.J., Tanaka, F., Robistschek, J., Markovic-Plese, S., Raye, A., Sandoval, C.M., Fischbeck, K. H.: Aggaresomes Protect Cells by Accelerating the Degradation of Polyglutamine-Containing Protein, Hum. Molec. Genet. Vol 12, No7: 749-757, 2003 Markovic-Plese, S., Cortese, I., Wendinger, K.P., McFarland, H.F., Martin, R.: CD4+CD28- Costimulation-Independent T-Cells in Multiple Sclerosis, J. Clin Invest. 108:1185-1194, 2001 Kondo, T., Cortese I., Markovic-Plese, S., Wandinger, K.P., Carter C., Brown, M., Leitman, S., Martin, R.: Dendritic Cell-T Cell Interactions in the Absence of Exogenous Antigen Mediate a Unique Pattern of Activation, Nature Immunol , 2 (10): 932-938, 2001 Zhao, Y., Gran, B., Pinilla, C., Markovic-Plese, S., Hemmer, B., Tzou, A., Whitney, L., Biddison, W, Martin, R., Simon, R.: Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic T-Cell Receptors and MHC-Peptide Ligands, J. Immunol 167: 2130-2141, 2001 Martin, R., Gran, B., Zhao, Y., Markovic-Plese, S., Bielekova, B., Marques, A., Sung, M.H., Hemmer, B., Simon, R., McFarland, H., Pinilla, C.: Molecular Mimicry and Antigen-Specific T Cell Response in Multiple Sclerosis and Chronic Central Nervous System Lyme Disease, J. Autoimmun, 16(3):187-192, 2001 Arndt, S.O., Vogt, A.B., Markovic-Plese, S., Martin, R., Moldenhauer, G., Wölpl, A., Sun, Y., Schadendorf, D., Hämmerling G.J., Kropshofer, H.: Functional HLA-DM on the Surface of B Cells and Immature Dendritic Cells, EMBO J. 19 (6): 1241-1251, 2000. Markovic-Plese, S., Pinilla, C., Martin, R.: Molecular Mimicry in Multiple Sclerosis: New Insights from Studying T Cell Receptor Degeneracy. Immunology News, Vol 6: No 4, 1999 Markovic-Plese, S., Fukuara, H., Zhang, J., Al-Sabbagh, A., Southwood, S., Sette, A., Kuchroo, V.K., Hafler, D.A.: T Cell Recognition of Immunodominant and Cryptic Proteolipid Protein Epitopes In Humans. J. Immunol. 155: 982-992, 1995.


Zhang, J., Markovic-Plese, S., Lacet, B., Raus, J., Weiner, H.L., Hafler, D.A.: Increased Frequency of Interleukin 2-Responsive T Cells Specific for Myelin Basic Protein and Proteolipid Protein in Peripheral Blood and Cerebrospinal Fluid of Patients with Multiple Sclerosis. J. Exp Med. 179: 973-984, 1994 Markovic, S., Bozicevic, D., Simic, D., Brzovic, M.: Genetic Markers in the Blood of Patients with Multiple Sclerosis. Neurol. Croat. 41 (1-2): 3-12, 1992 Jadro-Santel, D., Markovic, S., Besenski, N., Kalousek, M.: Correlative Tissue Pathology of Intracranial Neurinomas with Computed Tomography Scans. Neurol. Croat. 40 (1): 13-23, 1991

Other Peer Review Articles:

Mark S. Freedman, Johanne M. Kaplan, Silva Markovic-Plese: Insights into the Mechanisms of the Therapeutic Effect of Alemtuzumab in Multiple Sclerosis, Journal of Clinical and Cellular Immunology, In press, 2013

Broux, B., Markovic-Plese, S., Stinissen, P., Hellings. N.: Pathogenic features of CD4(+)CD28(-) T cells in immune disorders. Trends Mol Med. 2012 Jul 9. [Epub ahead of print] Ramgolam, V.S., Markovic-Plese, S: Regulation of suppressors of cytokine signaling as a therapeutic approach in autoimmune diseases, with an emphasis on multiple sclerosis. J Signal Transduct. 2011;635721. Epub 2011 Nov 1. Sha, Y., Markovic-Plese, S: A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases, Self/Nonself, 2011, 2(1):35-42. Zhang, X., Markovic-Plese, S: Interferon beta inhibits the TH17 cell-mediated autoimmune response in patients with relapsing remitting multiple sclerosis, Clin Neurol Neurosurg, 2010, 112:641-645 Ramgolam, V., Markovic-Plese, S: Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclersosis, End, Met Imm Disorders, 2010, 10 (2): 161-167 Ramgolam, V., Markovic-Plese, S.: Interferon-beta Inhibits Th17 Cell Differentiation in Patients with Multiple Sclerosis, Endocrine Metabolic Immune Disorders-Drug Targets, April 2010, [Epub ahead of print]

Markovic-Plese, S.: Degenerate TCR Recognition, Autoreactive T-cells, and the Autoimmune Response in Multiple Sclerosis, An Update, The Neuroscientist, 15(3): 225-231, 2009

Xin Zhang, Silva Markovic-Plese: Statins’ Immunomodulatory Potential Against Th-17 -mediated Autoimmune Response. Immunologic Research. 2008, 41(3): 165-74.


Markovic-Plese, S. The Genetics of Multiple Sclerosis, In: MS News Online, CME-Certified Series by Discovery Institute of Medical Education, Chicago. Available at www.msnewsonline.com, December 17, 2007. Markovic-Plese, S. Modulation of Inflammatory Response in Multiple Sclerosis by Altered Peptide Ligand, MSQR, 24: 5-9, 2005 Markovic-Plese. S., B., Pinilla, C., H.F., Martin, R. The Initiation of Autoimmune Response in Multiple Sclerosis, Clin Neurol Neurosurg, 106(3):218-222, 2004 Markovic-Plese, S.: The Immunological Basis of Multiple Sclerosis: Progress towards a Better Understanding of the Disease, MSQR, 21 (3): 1-7, 2002 Markovic-Plese, S., McFarland H.F.: Immunopathogenesis of the Multiple Sclerosis Lesion: Current View, Current Neurology and Neuroscience Reports, I:257-262, 2001 Markovic-Plese, S: Molecular Mimicry in Neurological Diseases, The Neuroscientist, 6(6): 428-432, 2000 Markovic-Plese, S., Pinilla, C., Martin, R.: Molecular Mimicry in Multiple Sclerosis: New Insights from Studying T Cell Receptor Degeneracy. Immunology News, Vol 6: No 4, 1999

Published Abstracts:

Tao, Y., Zhang, X., Weinstock-Guttman, B., Hayward, B., Dangond, F., ZIvadinof, R., Markovic-Plese, S.: Interferon beta-1a treatment inhibits Th1 and Th17-cell responses in patients with relapsing remitting multiple sclerosis, American Academy of Neurology, 2013 Annual Meeting, San Diego, CA Markovic-Plese, S.: Insufficent endogenous interferon-beta (IFNb) signaling may contribute to the susceptibility for multiple sclerosis. Implications for the IFNb's therapeutic mechanisms of action, 6th Dubrovnik International Conference on MS, Dubrovnik, Croatia, Neurologia Croatica, 2012 Zhang, X., Tao, Y., Chopra, M., Troiani, L., Marcus, K., Choudhary, N., Wray, S., Krolczky S., Markovic-Plese, S.: Alemtuzumab (anti-CD52 mAb) induces expansion of Treg and Th2 cells and inhibits Th1 and Th17 cells in treated patients with relapsing remitting multiple sclerosis (RRMS), AAN annual meeting, New Orleans, LA, May, 2012 Tao, Y., Zhang, X., Bhatt, N., Marcus, K.L., Markovic-Plese, S.: TLR7/9 agonists enhance therapeutic IFNβ-1a’s effect on the induction of immunomodulatory cytokine secretion via restoring an insufficient IFNAR/TLR signaling in monocytes derived from patients with RR MS, 4th Annual International Congress of Antibodies (ICA-2012), Beijing, China, March, 2012 Blauth, K., Zhang, X., Marcus, K., Bruce, D., Chopra, M., Troaini, L., Markovic-Plese, S.: Uncovering roles for fractalkine in CD4+ T cell migration into the central nervous system in patients with relapsing remitting multiple sclerosis, 40th Keystone Symposia, Breckenridge, CO, Jan 2012


Zhang, X., Tao, Y., Marcus, K., Chopra, M., Troiani, L., Markovic-Plese, S.: Alemtuzumab (anti-CD52 mAb) administration induces a significant expansion of T-regulatory cells, increased TGF�, IL-10 and IL-4 and decreased IFN-� and IL-17 production in the ex-vivo separated CD4+ cells from treated patients with relapsing remitting multiple sclerosis, European/American Committee for Treatment and Research in MS ECTRIMS/ACTRIMS annual meeting, Amsterdam, NE, Sept, 2011 Tao, Y., Zhang, X., Jin, J., Tang, Y., Troiani, L., Markovic-Plese, S.: Deficient endogenous interferon beta signaling is associated with pathogenic cytokines secretion profile from monocytes and CD4+ T-cells in patients with multiple sclerosis, American Academy of Neurology, 2011 Annual Meeting, Honolulu, Sha, Y., Troiani, L., Chopra, M., Markovic-Plese, S: IL1R1 induces human Th17 cell differentiation in an IRF4-dependent manner, 97th American Association of Immunologists Meeting, 2010, Baltimore, MD Zhang, X., Tao, Y., Troiani, L., Jin, J., Tang, Y., Markovic-Plese, S.: Exogenous intereferon beta (IFNB)-1a restores deficient endogenous IFNb/endosomal TLR signaling in patients with relapsing remitting multiple sclerosis, 7th International Congress on Autoimmunity, 2010, Ljubljana, Slovenia Zhang, X., Tao, Y., Jin, J., Tang, Y., Markovic-Plese, M.: IL-11 producing cells are a new T-cell subset that promotes Th17 differentiation in patients with clinically isolated syndrome suggestive of multiple sclerosis, American Academy of Neurology, 2010 Annual Meeting, Toronto, Canada Zhang, X., Choudhary N., Markovic-Plese, S.: Alemtuzumab therapy selectively depletes Th1 and Th17, but induces Treg cells in-vivo in patients with relapsing remitting multiple sclerosis, BIT’s 2nd Annual International Congress of Antibody-2010, Bejing, China Zhang, X., Tao, Y., Wang, J., Markovic-Plese, S: Simvastatin inhibits Th17 cell differentiation in patients with relapsing remitting multiple sclerosis, American Neurological Association, 134th Annual Meeting, 2009, Baltimore, MD Zhang, X., Tao, Y., Jin, J., Tang, Y., Markovic-Plese, S.: A critical role of Th17 cells in the initiation of autoimmune response in early multiple sclerosis (MS), Ist International Conference on Immune Tolerance, 2009, Boston, MA Ramgolam, S., D. Speer, N. Choudhary, and S. Markovic-Plese. Interferon beta (IFNB)-1b changes B-cell cytokine secretion orofile and inhibits Th17 cell differentiation. Neurol Suppl. 3. A104-105, 2009. Presentation Chosen for Multiple Sclerosis Scientific Highlights Session of AAN. Markovic-Plese, S.: Mechanisms of endogenous interferon beta immunoregulation, 5th Dubrovnik International Conference on Multiple Sclerosis, Dubrovnik, Croatia, 2009, Neurologia Croatica


Zhang, X., Speer, D., Markovic-Plese, S.: Statins affect Th17-mediated autoimmune respo;nse in multiple sclerosis, J Neuroimmunol, Issue 2, Vol 203, 2008, 9th International Congress of Neuroimmunology, Forth Worth, Texas Zhang, X., Tang, Y., Rogan, S., Jin, J., Speer, D., Markovic-Plese, S.: Differential gene and protein expression profiles in patients with clinically isolated syndrome (CIS) suggestive of MS, Mult Scler, Suppl 1, Vol 14, P689, World Congress on Treatment and Research in Multiple Sclerosis, Motreal, Canada Zhang, X., Rogan, S., Jin, J., Speer, D., Markovic-Plese, M.: Proteomic Characterization of Cerebrospinal Fluid and Genomic Characterization of Preripheral Blood Mononuclear Cells in Patients with Clinically Isolated Syndrome Suggestive of Multiple Sclerosis, Neurol Suppl 1, Vol 70, P7.132, 60thAnnual Meeting of the American Academy of Neurology, Chicago, IL, 2008 Zhang, X., Tang, Y., Montes, M., Jin, J., Ramgolam, V., Markovic-Plese, S.: Interferon Beta-1a Modulates the Innate Immune Response-mediated Regulation of Adaptive Immunity in Early Multiple Sclerosis, Neurol Suppl 1, Vol 70, P7.130, 60thAnnual Meeting of the American Academy of Neurology, Chicago, IL, 2008 Markovic-Plese, S., Speer, D., Jin, J., Chen, Y., Smrtka, J., Ingram, L., Jewells, V.L: Statin and Intramuscular Interferon Beta-1a Combination Therapy is Safe and Well-tolerated in Patients with Clinically Isolated Syndrome Suggestive of Multiple Sclerosis, a Pilot study, Multiple Sclerosis, Suppl 2, Vol 13, 2007.

Zhang, X., Montes, M., Jin, J., Tang, Y., Peng, X., Sujkowska, D., Markovic-Plese, S. Transcriptional and Proteomic Profiling of Statins’ Immunomodulatory Effect in Multiple Sclerosis, Neurol Suppl 1, Vol 68, 2007. Presentation Chosen for Multiple Sclerosis Scientific Highlights Session of AAN. Zhang, X., Tang, Y., Montes, M., Jin, J., Ramgolam, V., Markovic-Plese, S. Interferon Beta-1a Modulates the Innate Immune-response-mediated Regulation of Adaptive Immunity in Early Multiple Sclerosis; 94th Annual Meeting of the American Association of Immunologists, Miami Beach, FL, 2007. Jewells, V.L., Chin, B., Sayad, C., Smrtka, J., Markovic-Plese, S., Lin, W.: Comparison of 3T and 1.5T T2 lesion load in Multiple Sclerosis and Clinically Isolated Syndrome Patients, Clinical Implications. ASNR, Chicago, IL, 2007 Jewells, V.L., Chen, Y., Sayad, C., Smrtka, J., Markovic-Plese, S., Zhu, H., An, H., Bullitt, E., Lin, W.: Spatially Normalized Analysis of Diffusion Tensor Imaging in Clinically Isolated Syndrome and Multiple Sclerosis Patients, ASNR, Chicago, 2007 Montes, M., Kondo, T., W. Bruck, W., Jewells, V., Armao, D., Smrtka, J., Pinilla, C., Markovic-Plese, S.: Characterization of Oligoclonally Expanded T-Cells Derived from Multiple Sclerosis (MS) Lesions, The 8th International Congress of Neuroimmunology, Nagoya, Japan, 2006 Markovic-Plese, S, Sujkowski, D, Tang, Y, Martin, R, Pinilla, C: Characterization of CD4+ Cells with High Degree of TCR Flexibility in Patients with MS, American Association of Immunologyst annual meeting, Boston, MA, 2006.


Montes, M, Jewells V, Armao D, Smrtka J, Tang, Y, Sujkowski, D, Markovic-Plese, S: Characterization of T-Cells Derived from Acute and Chronic Multiple Sclerosis Lesions, Neurol. Suppl 2., Vol 66, No5, S42.005, 2006. Presentation Chosen for Multiple Sclerosis Scientific Highlights Session of AAN. Jewells, V., Chen, Y., Markovic-Plese, S., Smrtka, J., Lin, W. Identifying White Matter Abnormalities with Diffusion Tensor Imaging in CIS Patients, 19th Annual Meeting Of The Consortium Of Multiple Sclerosis Centers, Orlando, FL, 2005 Kasper, L.H., Everitt, D., Leist, T., Markovic-Plese, S., Ryan, K., Mascelli, M., Cusmano, C., Johnson, K., Hartnett, K., Bauman, C., Fadul, C., Pendley, C., Smith, J., Vollmer, T.: Safety, Pharmacokinetic, and Biological Response Profile of an IL-12p40 Antagonist in MS: A Phase I Clinical Trial, ECTRIMS meeting, Vienna, Austria, 2004 Markovic-Plese, S., Peng, X., Giri, S., Sujkowski, D., Singh, I. Immunomodulatory Effects of Simvastatin in Relapsing-Remitting, Multiple Sclerosis, 7th International Congress of Neuroimmunology, Venice, Italy, 2004 Markovic-Plese, S., Hemmer, B., Zhao, Y., Pinilla, C., Martin, R. T-Cell Receptor Degeneracy of a Highly Specific Influenza Haemagglutinin-Reactive CD4+ T-Cell Clone, 12th International Congress of Immunology, Montreal, Candada, 2004 Markovic-Plese, S.: The Initiation of Autoimmune Response in Multiple Sclerosis, Neurol.Croat, 52:21, 2003 Vollmer, T., Durkalski, V., Tyor, W., Corboy, J., Preiningerova, J., Markovic-Plese, S., Rizzo, M., Key, L., Singh, I.: An Open-Label, Single Arm Study of Simvastatin as a Therapy for Multiple Sclerosis, Neurol. Suppl., Vol 60, No5, S11.003, 2003 Markovic-Plese, S., Powell, A.W., Cortez, A., Vollmer, T.L.: Therapeutic Potential of Statins in Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis, Vol 8, Suppl. 1, P340, 2002 Vollmer, T.L., Preiningerova, J., Markovic-Plese, S., Rizzo, M.A., Cutter, G.: A Phase II b Study of Oral Interferon Beta-1a at Two Doses in Relapsing-remitting Multiple Sclerosis Using MRI, Clinical and Immunologic Measures, Multiple Sclerosis, Vol 8, Suppl. 1, P163, 2002 Markovic-Plese, S., Bielekova B., Kadom, N., Richert, N.D., Martin, R., McFarland H.F. Longitudinal Magnetic Resonance Imaging Study of the Effect of Azathioprine in Relapsing-Remitting Multiple Sclerosis Patients Refractory to the Treatment with Interferon ��1b, Neurol. Suppl, Vol 58, No3, A492, 20002 Markovic-Plese, S., Gran, B., Pinilla, C., McFarland, H.F., Martin, R. MHC-Biased Combinatorial Peptide Libraries Permit the Characterization of T-Cells with a High T Cell Receptor Degeneracy in Patients with Multiple Sclerosis, Nurol. Suppl, Vol 56, No3, A304, 2001


Markovic-Plese, S., Wendinger, K.P., Martin, R.: Characterization of CD4+ CD28-Costimulation Independent Lymphocytes in Multiple Sclerosis, Neurol Suppl, Vol 54, No 7, A148, 2000 Markovic-Plese, S., Fukoara, H., Al-Sabbagh, A., Sette, A., Kuchroo, V., Hafler, D.A.: T Cell Recognition of Immunodominant and Cryptic Proteolipid Protein Epitopes in Humans, Journal of Neuroimmunology, Vol. 54, 179: P06.12, 1994 Hafler, D.A., Markovic-Plese, S., Fukaura, H., Al-Sabbagh, A., Kuchroo, V., Southwood, S., Sette, A.: Characterization of MHC Binding and T-Cell Recognition of Immunodominant Proteolipid Protein Epitopes, The FASEB Journal Vol . 8, No. 4: A1143, 1994 Markovic-Plese, S., Fukuara, H., Al-Sabbagh, A., Southwood, S., Sette, A., Weiner, H.L., Kuchroo, V., Hafler, D.A.: Characterization of MHC Binding and T-Cell Recognition of Immunodominant Proteolipid Protein (PLP) Epitopes, Neurology Suppl. Vol. 44, No. 4: A 243, 1994 Zhang, J., Markovic, S., Hohol, M., Khoury, S., Raus, J., Weiner, L.H., Hafler, D.A.: Increased Frequency of IL-2 Responsive T Cells Specific for Myelin Basic Protein and Proteolipid Protein in Blood and Cerebrospinal Fluid of Patients with Multiple Sclerosis, Neurology Suppl. Vol. 43, No. 4: A 355, 1993 Poljakovic, Z., Klein-Pudar, M., Markovic, S., Pemov, P., Reic, P., Dimitrijevic, J., Povse, M., Arbutina, M., Zikic, M.: Incidence of Cerebrovascular Stroke in Yugoslavia, 5th Yugoslav Symposium on Cerebrovascular Diseases, Zagreb, Croatia, 1990 Radocaj, M., Markovic, S., Poljakovic, Z., Klein-Pudar, M., Turek, S.: The Risk Factors for Cerebrovascular Diseases, 5th Yugoslav Symposium on Cerebrovascular Diseases, Zagreb, Croatia, 1990 Klein-Pudar, M., Luetic, V., Poljakovic, Z., Markovic, S.: The Results of Longtime Follow-Up of Surgically Treated Patients with Stenotically Changed Extracranial Blood Vessels, 5th Yugoslav Symposium o Cerebrovascular Diseases, Zagreb, Croatia, 1990

Refereed unpublished presentations:

Markovic-Plese, S.: Current and emerging therapies for MS, Adriatic Neurology Forum, Dubrovnik, Croatia, 2012

Markovic-Plese, S.: Pediatric MS; To treat or not? Congress Controversies in Neurology, Opatija, Croatia, 2008 Jewells, V.L., Chen, Y., Sayed, C., Zhu, H., Smrtka, J., Speer, D., Markovic-Plese, S., An, H., Lin, W.: DTI Voxel Based Analysis and ROI Analysis of Clinically Isolated Syndrome and Multiple Sclerosis Patients at First Time Point as well as Sequentially at

Multiple Time Points; 23rd Radiology Symposium University of North Carolina, Chapel Hill, NC, 2007.


Lahoud, R., Montes, M., Sujkowski, D., De Marchena, L., Misaghian, N., Markovic-Plese, S.: AICAR (5-Aminoimidazole-4-Carboxamide Ribonucleoside): Possible Role in the Treatment of Multiple Sclerosis, University of North Carolina at Chapel Hill, 39th annual Medical Student Research Day, 2006 Markovic-Plese, S., Arndt, S.O., Vogt, A.B., Hammerling, G.L., Martin, R., Kropshofer, H.: HLA-DM Controls Peptide Exchange and Immunodominance in the MHC Class II Recycling Pathway, FASEB Autoimmunity Research Conference, Vermont Academy, 1999 Markovic-Plese, S., Gran, B., Pinilla, C., Hemmer, B., Zhao, Y., Martin, R.: Determining the Fine Specificity of Autoreactive T Cell Clones Using Synthetic Peptide Combinatorial Libraries, National Institute for Neurological Diseases and Stroke Retreat, Bethesda, MD, 1999 Patva, H., Markovic-Plese, S., Novella, S., Lesser, D., Goldstein J.M.: The Effect of Immunosuppression on Generalization in Ocular Myasthenia Gravis, Eighth Meeting of the European Neurological Society, Nice, France, 1998 Markovic-Plese, S., Juedes, A., Suen, W. E., Hjelmstrom, P., Ruddle, N.: The Role of Lympotoxin in Determinant Spreading and EAE, 7th International TNF Congress, Hyannis, MA, 1998 Poljakovic, Z., Klein-Pudar, M., Dugonjic, A., Markovic, S.: Epidemiology of Cerebrovascular Disease - Comparative Study - Cerebrovascular Stroke, Diabetes Mellitus and Myocardial Infarction, 1st International Stroke Congress, Kyoto, Japan, 1989 Teaching Record:

• Course Director: MCRO 712 Winter 2009 Seminar/Tutorial, Interaction of the Innate and the Adaptive Immune Response in the Development of Autoimmune Response, Immunology and Microbiology Graduate Program, 8-12/2009 MCRO 712 Spring 2007 Seminar/Tutorial, Autoimmunity and the Breakdown of Immune Tolerance, Immunology and Microbiology Graduate Program, 1-5/2007

• Lectures: Lectures to Medical Students:

Multiple Sclerosis, Clinical Presentations and Treatment Options MSY4 Medical Students monthly noon conferences, UNC Chapel Hill School of Medicine, 2003-present Neurobiology of Diseases Course, MSY1 and MSY2 Medical Students, UNC Chapel Hill School of Medicine, 2003-2009 Multiple Sclerosis, Diagnosis and Treatment, MSY3 Lecture, UNC Chapel Hill School of Medicine, 2003-2008 Neuroinflammatory Diseases, MSY3 Lecture, Yale School of Medicine, Spring 2003


Introduction to Neurological Diseases, MSY2 Course, Yale School of Medicine, Spring 2003 Neurology Clerkship Lectures for Medical Students, Yale School of Medicine, Spring 2002 Lectures to Graduate Students: 228 NBIO UNC, Central Nervous System Inflammatory Diseases, Neurobiology Graduate Program, 2003-2008 Lectures to Residents: Neuroinflammatory Diseases, Overview and Board Exam preparation, 2010 Neuromyelitis Optica, UNC-Chapel Hill, Department of Neurology, 2009 Acute Disseminated Encephalomyelitis, UNC-Chapel Hill, Department of Neurology, 2008 Diagnostic Workup for Inflammatory CNS Diseases, Neurology Resident Lecture Sries, UNC-Chapel Hill, Department of Neurology, 2007 Disturbances of Cognition and Affect in Multiple Sclerosis, Psychiatry Resident Lecture, UNC-Chapel Hill School of Medicine, 2006 Use of MRI in Diagnosis of Multiple Sclerosis, Neurology Resident Lecture Series, UNC-Chapel Hill, Department of Neurology, 2005 Early Diagnosis of Multiple Sclerosis, Neurology Resident Lecture Series, UNC-Chapel Hill, Department of Neurology, 2004 Neurological Examination, Neurology Resident Series, Yale School of Medicine, 2003 Mechanisms of Inflammatory Cell Migration from Peripheral Circulation to the CNS, Neurology Resident Series, Yale School of Medicine, 2002 Treatment Algorithms for Multiple Sclerosis and Other Demyelinating CNS Diseases, Neurology Resident Series, Yale School of Medicine, 2002 Guillian Barre Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy, Neurology Resident Series, Yale School of Medicine, 2001 Diagnostic Workup for Multiple Sclerosis, Neurology Resident Series, Yale School of Medicine, 2001 Grand Rounds at UNC: Multiple Sclerosis, Overview of the Disease Pathogenesis and New Therapies, Physical Medicine and Rehabilitation Grand Rounds, University of North Carolina at Chapel Hill, NC, 2/13


Deficient Endogenous Interferon-b Secretion and Signaling Disinhibit Th17-cell mediated Autoimmune Response in Relapsing-Remitting Multiple Sclerosis, Neurology Grand Rounds, University of North Carolina at Chapel Hill, NC, 1/13 Alemtuzumab (anti-CD52 mAb) Treatment Induces Long-lasting Suppression of Disease Activity in Patients with Relapsing Remitting Multiple Sclerosis, Neurology Grand Rounds, University of North Carolina at Chapel Hill, NC, 2/10 Pathogenesis of Multiple Sclerosis and Current Research, Neuroscience Seminar: University of North Carolina, Chapel Hill, NC, 7/05 Immunopathogenesis of Multiple Sclerosis, Department of Microbiology and Immunology Grand Rounds, University of North Carolina, Chapel Hill NC, 9/03 Immunological Basis of Multiple Sclerosis, Neurology Grand Rounds, University of North Carolina at Chapel Hill, NC, 12/02

Grand Rounds Outside UNC: Decreased endogenous interferon (IFN)� secretion contributes to the Th17 cell-mediated autoimmune response in relapsing remitting multiple sclerosis, University of Wisconsin, Madison, WI, 1/12 IL-11-producing CD4+ T-cells induce Th17-cell differentiation in patients with clinical onset of relapsing remitting multiple sclerosis, Institute for Multiple Sclerosis, Gottingen Medical University, Gottingen, Germany 4/11 Biomarkers of clinically isolated syndrome suggestive of multiple sclerosis, University of Hasselt, Hasselt, Belgium, 4/11 Simvastatin Inhibits Interferon Regulatory Factor 4 Expression and Th17-cell Differentiation in CD4+ T-cells Derived from Patients with Multiple Sclerosis, Max-Planck Institute for Experimental Biology, Gottingen, Germany, 3/11 Immunomodulatory Effects of Statins, Department of Microbiology and Immunology Seminar, East Carolina University, Greenvile, NC, 10/10 Characterization of T-cell Infiltrates Derived from MS Lesions at Various Stages of Progression, Neurology Grand Rounds, Johns Hopkins University, MD, 3/07 T-cell Receptor Usage Analysis in the T-cell Infiltrates Derived from MS Lesions, Neuroimmunology Grand Rounds, University of Maryland, MD, 3/07 Statins as a New Immunomodulatory Therapy for Multiple Sclerosis, Neurology Grand Rounds, Yale University, CT, 4/03 Therapies for Newly Diagnosed Multiple Sclerosis Patients, National Multiple Sclerosis Society, Greater Connecticut Chapter, Newington, CT, 10/01 Multiple Sclerosis, Department of Rheumatology Grand Rounds, Duke University, NC, 1/00


New Therapies for Multiple Sclerosis, Grand Rounds, Gaylord Hospital, Wallingford, CT, 1/98 Neurosarcoidosis: Diagnostic Studies and Treatment Options, Neurology Grand Rounds, Yale School of Medicine, CT, 10/97 Continuing Education Lectures at UNC: Multiple Sclerosis, AHEC broadcasted lecture, University of North Carolina, School of Public Health, Chapel Hill, NC, 10/07 Update in Therapies of Multiple Sclerosis, AHEC broadcasted lecture, University of North Carolina, School of Public Health, Chapel Hill, NC, 10/05 Multiple Sclerosis and Its Differential Diagnosis, AHEC broadcasted lecture, University of North Carolina, School of Public Health, Chapel Hill, NC, 10/04 The Cutting Edge: Hot Topics in Neurology and Neurosurgery, University of North Carolina School of Nursing, Chapel Hill, NC, 4/04 Inflammatory Diseases of the Central Nervous System, UNC-School of Medicine Alumni Meeting, Chapel Hill, NC, 10/03 About Multiple Sclerosis and the New UNC MS Clinic, UNC-School Of Medicine, Raleigh NC, 9/03

Continuing Education Lecture outside of UNC:

Demyelinating Diseases That Mimic Multiple Sclerosis, National Multiple Sclerosis Society, 2006 Carolinas Consortium, Charlotte, NC, 10/06 Empowerment Program for Newly Diagnosed MS Patients, National MS Society, Eastern North Carolina Chapter, Raleigh, NC, 6/05 Unlocking the Mysteries of MS, National MS Society, Raleigh, NC, 6/04 Multiple Sclerosis: Balancing the Challenges of Body, Mind and Spirit, National MS Society, Eastern North Carolina Chapter, Chapel Hill, NC, 9/03 Future Directions in Research on Multiple Sclerosis, Wake AHEC, Raleigh, NC, 9/03

Lab or Research Teaching/Mentorship:

Mentor for PhD thesis for neurobiology graduate student Kevin Blauth, 2/2010-9/2012 graduated 9/12, Thesis: Fractalkine Induces the Expression of Intercellular Adhesion Molecule-1 on CD4+ T-lymphocytes: implications for the immunopathogenesis of Multiple Sclerosis, currently postdoctoral fellow at the Department of Neurology, University of Colorado, Denver Postdocrotal fellowship mentor for Danny Bruce, PhD, 1/10-12/12, Yazhong Tao, PhD, 9/2009-present, Yonggang Sha, PhD, 2008-2011, Xin Zhang, MD, 2006-present, Vinod Rangolam, PhD, 2006-2009, Monica Montes, PhD, and Yunan Tang PhD, 2005-2007, UNC Chapel Hill


Research mentor for research assistant Karen Marcus 2010-2012, Neelima Choudhary 2008-2009, Jinzhao Wang, 2007-2008, Danuta Sujkowski, 2003-2006, UNC Chapel Hill Research Advisor for MD/PhD Student Y II Summer Research Program Sarah Rogan, recipient of Carolina MD/PhD Student Research Fellowship, 2006, UNC Chapel Hill Research Advisor for UNC Medical Student YI Michael Gentry, 2008; UNC Medical Student YII Seble Chekol, 2006, recipient of the Holderness Medical Fellowship, UNC Chapel Hill Summer Research Program, Rony Lahoud, 2005. Research Advisor for Immunology and Microbiology Graduate Students, laboratory rotation, Julia Malik, 4/12-10/12, Lydia Aybar, 2007; Lisa Leightly, 2006; Laura De Marchena 2005, UNC Chapel Hill Research Advisor For Undergraduate Students, Ashcon Livingston, 2012-present, Kinnari Buch 2013-present, Maheer Masood 2011-paresnt, Ashley Russo 2010-2012; Biology 98A, Bo Han 2003, Negin Misaghian 2003-2006, UNC Chapel Hill Research mentor for research associate Xue-Yan Peng MD, PhD and research assistant Ashton Powel, 2001-2003, Yale School of Medicine

Clinical Teaching: Clinical and Research Mentor for the neuroimmunology clinical fellow Lee Harsell, MD, MA 2011-2012, physician assistant Clara Zelasky 2013-present, Luigi Troiani, 2009-2012, nurse practitioner Danielle Speer UNC-Chapel Hill School of Medicine, 2006-2008, Mentor for the grant application “Reproductive Decisions, Pregnancy and Parenthood in Multiple Sclerosis” funded by the International Organization of Multiple Sclerosis Nurses (IOMSN), 2008; Clinical Mentor for Jennifer Smrtka, NP, 2003-2006; Clinical Mentor for study coordinator: Manisha Chopra 2009-present, Liseanne Fedor-Hammnods, 2007-2008; Cynthia Kenan, UNC-Chapel Hill School of Medicine, 2003-2006 Clinical teaching for students and residents rotating through neuroimmunology clinic, and neurology service, UNC-Chapel Hill School of Medicine, 2003-present Clinical Mentor: Amy Toenjes, nurse practitioner, Neuroimmunology Clinic, Yale University, 2002-2003 Neurology Inpatient and Consult Service, Neuroimmunology Clinic teaching and supervision of medical students, neurology, psychiatry, and internal medicine residents, Yale School of Medicine, 2001-2003,

Graduate Committees: Microbiology and Immunology Graduate Disertation Committee, The role of NLRP4 in the development of the autoimmune response, Less Freeman, 2011-present Cell and Molecular Physiology Graduate Dissertation Committee: Defining the molecular role of Whirlin in myelinated axons, James Green, 2010-2013


Microbiology and Immunolgy Graduate Program: Oral Preliminary Exam, Flor Evangelista, 2010 Immunology Graduate Dissertation Committee: Influence of Gender on Cuprizone-Induced CNS Demyelination and Remyelination with an Emphasis on the Role of Estrogen, Lorelei Taylor, 2005-8 Immunology Graduate Dissertation Committee: IL-1 Promotes Remyelination in the Cuprizon-Induced Animal Model of MS, Vivian Susan Chen, 2005-8

Research grants: 20122013 The Role of IL-11+CD4+ T-cells in the Development of the Autoimmune

Response in MS, NMSS Research Grant The study will investigate the role of IL-11 in the development of the early

autoimmune response in MS, determine transcription profile, phenotype and function of IL-11-producing CD4 cells.

2012-present Investigator Initiated Study: Biomarkers of IFNb-1a’s Immunomodulatory

Effects Targeting TH17 cell-mediated responses, Biogen Idec, Markovic-Plese, PI The project will characterize IFNb-1a’s in-vivo effect on B-cells and Th cell subsets in patients treated with IFNb-1a IM.

2011-present T-Regulatory Cell-Mediated Reconstitution Of Immune Tolerance In

Alemtuzumab-Induced Lymphopenia, Genzyme, Inc. This study will characterize the therapeutic effects mediated via

expansion of T-regulatory cells in patients treated with I.V. Alemtuzumab in the extension phase of the clinical trial, Markovic-Plese PI

2011-2013 Rebif® Advanced MRI and Immunology Pilot Trial, Serono Inc.

Protocol # 29665 A twenty-four week, two arm, pilot trial to evaluate remyelination/demyelination, gray matter volume and iron deposition in the central nervous system (CNS) and immune status of subjects with relapsing-remitting multiple sclerosis (RRMS) treated with Rebif® 44 mcg subcutaneously (sc) three times a week (tiw) compared to a healthy control group, PI: R. Zivadinov, Markovic-Plese Co-PI

2010-2013 Charles Dana Foundation, Neuroimmunology Program: Th17 Phenotype of Auto-reactive T-cells in Patients with Relapsing Remitting Multiple Sclerosis The project will characterize antigen specificity and functional characteristics of Th17 T-cell clones derived from the peripheral blood and cerebrospinal fluid of patients with relapsing remitting multiple sclerosis, Markovic-Plese PI


2010-2012 Investigator Initiated Preclinical Study: Alemtuzumab-induced Prolonged

Suppression of the Autoimmune Response is Initiated During the Early Phase of the Immunological Reconstitution in Patients with Relapsing Remitting Multiple Sclerosis, Genzyme Inc, Markovic-Plese PI

2009-2012 National Multiple Sclerosis Society Research Grant: Immunomodulatory

Effects of Statins, Markovic-Plese PI 2009-2013 Investigator Initiated Study: Characterization of immunological

reconstitution following alemtuzumab therapy in patients with relapsing remitting multiple sclerosis, Genzyme Inc, Markovic-Plese PI

2008-2013 National Multiple Sclerosis Society Center Award: Novel Immune Pathwa

ys in MS Pathogenesis and Therapy, J. Ting PI, S. Markovic-Plese Co-PI 2007-2011 Investigator Supported Study, Charactetization of Interferon Beta-1b-

Induced Tolerizing Effect in Dendritic Cells, Bayer Inc., Markovic-Plese PI 2006-2010 Independent Medical Grant: Interferon Beta-1a Induction of Tolerizing

Effect in Dendritic Cells and Gamma Delta Cells on the Autoimmune Response in Multiple Sclerosis, Serono/Pfizer, Markovic-Plese PI

2005-2010 Independent Medical Grant: Gene Expression Analysis of the Effects of

Interferon �-1a and Atorvastatin Combination Treatment of Isolated Clinical Syndrome Suggestive of Multiple Sclerosis, Serono/Pfizer, Markovic-Plese PI

2004-2007 Investigator Initiated Study: Early IFN �-1a and Simvastatin Combination

Therapy in Clinically Isolated Syndrome Suggestive of MS, Biogen/Idec, Markovic-Plese PI

2003-2008 Career Development Award KO8 NS045871-01: The Mechanisms of

Autoimmune Response Initiation in Multiple Sclerosis, NINDS

2002-2004 In Vitro Assessment of the Therapeutic Potential of Simvastatin and Interferon �-1a Combination Therapy in Relapsing-Remitting MS, Biogen, Markovic-Plese PI

2002-2003 Investigator Initiated Study: Immunological Parameters of the Response

to Treatment with Monoclonal Anti-IL-12 Antibody in Patients with Relapsing-Remitting Multiple Sclerosis, Centocor, Markovic-Plese PI

Clinical Research: 2013-present Placebo controlled randomized withdrawal evaluation of the efficacy and

safety of baclofen ER capsules (GSR) in subjects with spasticity due to multiple sclerosis, Sun Pharma, Site PI


2013-present A 12-month, randomized, rater- and dose-blinded study to compare the efficacy and safety of fingolimod 0.25 mg and 0.5 mg administered orally once daily with glatiramer acetate 20 mg administered subcutaneously once daily in patients with relapsing-remitting multiple sclerosis, Novartis, Site PI

2011-2013 JCV antibody program in patients with relapsing multiple sclerosis

receiving or considering treatment with Tysabri, Biongen Idec, Site Principal Investigator, UNC Chapel Hill

2011-present A Phase II, Randomized, Double-blind, Parallel-group, Placebo-

controlled, Multicenter Study to Evaluate the Safety and Efficacy of Abatacept in Adults with Relapsing-remitting Multiple Sclerosis, NIH, NIAID, Immune Tolerance Network, Site Principal Investigator, UNC Chapel Hill

2008-present A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two

annual Cycle of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif) in Patients with Relapsing-Remitting Multiple Sclerosis Who Have Relapsed On Therapy, Genzyme Inc., Site Principal Investigator, UNC Chapel Hill

2006-2009 A 24-Month Double-Blind, Randomized, Multicenter, Placebo-Controlled,

Parallel-Group Study Comparing the Efficacy and Safety of 0.5 Mg And 1.25 Mg Fingolimod (FTY720) Administered Orally Once Daily Versus Placebo in Patients with Relapsing-Remitting Multiple Sclerosis, Novartis, Site Principal Investigator, UNC Chapel Hill

2005-2009 A Multi-Centered, Randomized, Double-Blind, Placebo Controlled Study Assessing the Add-On Effect of Oral Steroids in Relapsing Remitting Multiple Sclerosis Subjects Treated with Glatiramer Acetate, TEVA Neuroscience, Site Principal Investigator, UNC Chapel Hill

2004-2007 A Multi-Center, Randomized, Blinded, Parallel-Group Study of Avonex

Compared with Avonex in Combination with Oral Methotrexate, Intravenous Methylprednisolone, or Both in Subjects with Relapsing-Remitting Multiple Sclerosis who Have Breakthrough Disease on Avonex Monotherapy, Biogen/Idec, Site Principal Investigator, UNC Chapel Hill

2003 Safety, Tolerability and Activity Study of Oral Famperidine-SR in Subjects

With Multiple Sclerosis – Co-investigator, Yale School of Medicine 2002-2003 Phase II, Randomized, Double-Blind, Placebo-Controlled Study to

Evaluate the Preliminary Efficacy, Pharmacokinetics and Immunogenicity of BMS-188667 Administered to Subjects with Relapsing Remitting Multiple Sclerosis, Site Principal Investigator, Yale School of Medicine

2002-2003 A Phase I, Randomized, Double-Blind, Placebo-Controlled Study

Evaluating the Safety and Pharmacology of Single Subcutaneous Administrations of Human Monoclonal Antibody to IL-12 (CNTO 1275) in


Subjects with Relapsing Forms of Multiple Sclerosis- Site Principal Investigator, Centocor, Yale School of Medicine

2002-2003 An Open-Label, Single Arm Study of Simvastatin as a Therapy for

Multiple Sclerosis (MRI Outcome Measures) – Site Principal Investigator, Merck Pharmaceutical, Yale School of Medicine

2002-2003 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group,

Multicenter Study to Determine the Safety and Efficacy of Natalizumab in Subjects with Relapsing-Remitting Multiple Sclerosis, Co-Investigator, Yale School of Medicine

2001-2003 A Phase I Study of Autologous Schwann Cell Transplantation as a

Possible Reparative Therapy for MS, Co-Investigator, Yale School of Medicine

2001-2003 Open Label Study of the Safety and Tolerability of Combination Therapy

with Mitoxantrone (Novantrone) and Either Interferon �1a (Avonex) or Glatiramer Acetate (Copaxone)- Co-Investigator, Yale School of Medicine

2001-2003 Prospective, Open Label Tolerability and Safety Monitoring Study

of Novantrone in a Selected Cohort of Multiple Sclerosis Patients – Co-Investigator, Yale School of Medicine

2001-2002 A Double Blind, Dose Ranging Study of Fampridine-SR in Subjects with

Multiple Sclerosis –Co-Investigator, Yale School of Medicine 2001-2003 Open-Label Safety Extension Study of Avonex (Interferon Beta-1a)

Treatment in Subjects who Completed Biogen Studies C95-812, C96-823, Or C97-830 – Co-Investigator, Yale School of Medicine

2001-2003 Open Label, Randomized, Multicenter, Comparative, Parallel Group

Study of Rebif 44 Mcg Administered Three Times per Week by Subcutaneous Injection, Compared with Avonex 30 Mcg Administered Once per Week by Intramuscular Injection in the Treatment of Relapsing-Remitting Multiple Sclerosis – Co-Investigator, Yale School of Medicine

2001-2002 A Multi-National, Multi-Center, Double Blind, Placebo Controlled Study to

Evaluate the Efficacy, Tolerability, and Safety of Glatiramer Acetate for Injection in Primary Progressive Multiple Sclerosis Patients – Co-Investigator, Teva Neuroscience, Yale School of Medicine

1998 Effect of the Humanized Monoclonal Antibody Against the Interleukin-2

Receptor Alpha Subunit (IL-2R-Alpha; Zenapax®) on Inflammatory Activity in the CNS in MS in a Baseline-To-Treatment, Cross-Over, MRI-Controlled Single Center Phase I/II Trial - Co-nvestigator, Neuroimmunology Branch, NIH, NINDS

1997-1998 An Open-Label Dose Proportionality Study to Assess the Safety and


Tolerability and Pharmacokinetics of Escalating Doses of Fampridine (4-Aminopyridine) in Subjects with Multiple Sclerosis –Co-investigator, Yale School of Medicine

1995-1998 Open Label Study to Evaluate the Safety of Copaxone and to Monitor the

Neurologic Course of Disease in Multiple Sclerosis Patients Treated with Copaxone – Teva Neuroscience Co-Investigator, Yale School of Medicine

Professional Service: Since my arrival to Chapel Hill, I have established the first neuroimmunology/MS clinic at the University of North Carolina, which become recognized by National MS Society as one of their MS Centers in 2005. The clinic serves as a tertiary referral center for the state of North Carolina, and wider southeast area. Our clinical team includes physician assistant and study coordinator, and provides comprehensive care for MS patients. We work closely with number of general neurologists from the area who are routinely referring MS patients for diagnostic workup, treatment management and specific symptomatic or acute symptom treatment. We have established collaboration with the Urology, Ophtalmology, Radiology, PT/OT, and Neurosurgery services. We have been offering to our patient population since 2003 new treatment options through the clinical trials, particularly to the patients refractory to the first line therapies. Editorial Appointments: Editorial board membership: BMC Neurology 2011-present Frontiers in Neurology, 2012-present Journal of Clinical and Cellular Immunology, 2012-present Ad Hoc Reviewer for the following Journals: Acta Haemotologica, American Journal of Pathology, Archivum Immunologiae Therapiae Experimentalis, Atherosclerosis, Arthritis Research Therapy Journal, BMC Medical Genomics, Cellular and Molecular Life Sciences, Clinical Immunology, Clinical Neurology and Neurosurgery, Cytokine, Diabetologia, European Journal of Clinical Investigation, European Journal of Internal Medicine, European Journal of Pharmacology, Expert Opinion in Biological Therapy, Expert Review of Clinical Immunology, Expert Reviews, International Multiple Sclerosis Care, Journal of Clinical Immunology, Journal of Immunology, Journal of Molecular Cell Biology, Journal of Neuroimmunology, Journal of Neuroscience Research, Journal of Rehabilitation Research and Development, Neurology, Neuroscience Letters, Plos One, Thrombosis and Homeostasis.

Administrative Activities within UNC: Neurology Department Research Committee, member, 2009-present Chief, Neuroimmunology Division of the Department of Neurology, 2003-present Director, UNC Multiple Sclerosis Clinic, Department of Neurology, 2003-paresent Study Section Member:


NIH, NINDS, ad hoc study section member, clinical neuroimmunology an brain tumors (CNBT) , February 2011, February, June, October 2012 Research Foundation Flanders, Postdoctoral fellowship application review, 2012 National Multiple Sclerosis Society, US, pilot research grant proposal review, 2012 Health Research Board, Ireland, grant proposal review, 2011

United Kingdom National Multiple Sclerosis Society, grant proposal review, 2011

Medical Research Council, Great Britain, grant review, 2010 Fondazione Cariplo, Italy, grant proposal review, 2009 Immune Tolerance Network, NIH, grant concept proposal review, 2009 American National Multiple Sclerosis Society, Postdoctoral Fellowship

application review, 2009 Canadian National Multiple Sclerosis Society, study section member,

Pediatric Demyelinating Disease, 2008 Department of Defense Congressionally Directed Medical Research

Program, study section member, MS/Autoimmunity, 2008, 2009 Special Emphasis Panel, Collaborative Network for Clinical Research on Immune

Tolerance, NIH, NIAID, 9/2006 Research Statement: My research interests focus on the molecular events involved in the initiation of autoimmune response in MS and on the mechanisms of action of immunomodulatory and neuroprotective therapies for this disabling disease. Current projects in the laboratory include systematic search for viral, bacterial, and self-antigens that trigger the activation of pathogenic T cell clones in MS. We are presently pursuing studies that will determine to what degree the activation threshold of autoreactive pathogenic T-cells differs in patients with autoimmune diseases in comparison to healthy individuals. We have recently discovered that IL-11, a cytokine not previously studied in the context of autoimmunity was the strongest up-regulated cytokine in the CSF and serum of patients with clinically isolated syndrome suggestive of MS. Further studies have identified IL-11-producing CD4+ cells, whose transcriptional profile, phenotype and function is currently being characterized in the laboratory. Several Phase II-III clinical trails testing new therapies for MS are actively enrolling patients at the UNC MS Research Center. Presently, the effects of statins, the cholesterol-lowering agents which exhibit anti-inflammatory and neuroprotective effects, are studied in the laboratory. Our transcriptional profiling studies have identified the genes involved in the anitinflammatory effects of statins, and further characterization of their effect is currently underway. While IFNβ has been used over the past 20 years as a first line therapy for MS, its mechanisms of action are still not completely elucidate. Following several reports from our laboratory on the IFNβ’s selective in-vitro suppression of the pathogenic Th17 cells, we are now pursuing two studies on the treated patients with high and low dose IFNβ-1a in order to elucidate its in-vivo mechanisms of Th17 cell suppression in treated patients.


We have recently completed a longitudinal study on the immunological reconstitution following Alemtuzumab-induced lymphopenia in patients with relapsing remitting MS. Our results have identified that a relative expansion of Tregulatory cells, followed by the expansion of immunoregulatory Th2 cells, and the later suppression of the pathogenic Th1 and Th17 cells. We propose that this differential pattern of reconstitution of the individual T-cell subsets is an underlying mechanism for the long-lasting therapeutic effect of Alemtuzumab, which suppresses disease activity for 1-5 years following a single infusion cycle. Alemtuzumab is currently submitted for FDA approval as a treatment for MS, and future studies of its mechanisms of action are planned upon its approval. My clinical and laboratory research projects are well interconnected, and they had generated sufficient preliminary data for R21 and R01 grant proposal that are currently in submission, and NMSS research grant currently under review. Teaching Statement: Working with students from microbiology and immunology graduate program, MD and MD/PhD students, as well as UNC undergraduate students in the laboratory over the past several years has been a rewarding teaching experience. Over the past 3 years, several outstanding students have participated in our projects and presented their work at conferences. Recently, Kevin Blauth, a neurobiology graduate student has completed his graduate studies in our laboratory, defended his PhD thesis and graduated in October 2012. Prior to graduation he has received a first award for poster presentation at the UNC Department of Microbiology and Immunology Symposium. I particularly enjoyed teaching a graduate level course, which further enhanced my interaction with microbiology and immunology graduate students. Over the past years, I have actively participated in teaching medical students and residents in neurology and psychiatry. During my Neurology Inpatient and Consult Service Attending months, we have frequently discussed relevant publications in a journal-club format. In addition, residents attended my lectures and presentations on selected topics in neurology. I have also participated in continuing education programs for UNC nursing staff, Medical school alumni, and multiple education and counseling programs for patients and their families. Teaching is an integral part of my laboratory and clinical work, which I tremendously enjoy.

CURRICULUM VITAE Personal Information: Name: Silva Markovic ...

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