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David PerlinPhDExecutiveDirector andProfessorPublic HealthResearch

Project Summary:

In Vitro Screening (IVS) Core (F)

The IVS Core will provide to assess the antimicrobial efficacy of compoundsprovided by Projects 1­5. The Connell laboratory has developed an efficientmedium throughput screening system for determining MIC90 values using a96 well plate assay with appropriate statistical analysis, according to CLSImethodology. Antibiotic resistance will be determined for selected candidatecompounds and, as appropriate, compounds will be evaluated usingstandard assays for potential cytotoxicity, inhibition of metabolic activity, andinhibition of cell proliferation using mammalian cells in culture. In addition totraditional MICs, a number of specialized assays will be available forindividual project requirements. The resources and expertise of the IVSCore include macrophage infection model, concentration­dependent killingversus time­dependent killing, small colony variants, serum shiftexperiments, and drug combination analysis. Compound purity will beconfirmed working in conjunction with the Medicinal Chemistry Core (CoreD). Data conformity and storage will be handled and shared using theCollaborative Drug Discovery, Inc. software program (see Data Sharing).

The organisms in Connell’s collection include the ESKAPE pathogens, andother human pathogens of concern such as mycobacetrial and clostridialspecies, and Select Agents designated as potential biological weaponsagents. Dr. Barry Kreiswirth’s (PHRI) extensive collection of clinical strains,

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Institute CenterNew JerseyMedical SchoolRutgers, TheState Universityof New Jersey225 WarrenStreetNewark, NewJersey 07103 Phone: (973)854­3200Fax: 973­854­3201e­mail: perlinds@njms.rutgers.edu

Isabela DiasFreedman,Ph.D., D.V.M.ScientificAdministrator/ProjectCoordinator ­CETR Public HealthResearchInstitute &RegionalBiocontainmentLaboratoryRutgers ­ TheState Universityof New Jersey225 WarrenStreet, Newark,NJ 07103 USAEmail:isabela.dfreedman@rutgers.eduPhone: 973­972­9104Fax: 973­854­3201

assembled in collaboration with private, public and VA hospitals in the NewYork/New Jersey metropolitan area, as well as hospitals throughout theworld, will serve in later stages of the projects to define resistance profiles. BSL2, BSL3 and Select Agent BSL3 laboratories are provided for the safeuse of this extensive strain collection. The team assembled to carry outthese in vitro assays has a combined experience of over 65 years inbacetrial drug discovery and analysis of antibiotic susceptibility andresistance. The group's medium throughput experience with high precisionis a significant and essential contribution to the overall project’s success.

Biography:

Nancy D. Connell is Professor in the Division of Infectious Disease in theDepartment of Medicine at Rutgers New Jersey Medical School (RNJMS)and the Rutgers Biomedical Health Sciences. A Harvard University Ph.D. inMicrobiology, Dr. Connell’s major research focus is antibacetrial drugdiscovery in respiratory pathogens such as M. tuberculosis and B.anthracis. She is Director of the Biosafety Level Three (BSLIII) Facility ofRNJMS’s Center for the Study of Emerging and Re­emerging Pathogensand chairs the University’s Institutional Biosafety Committee. Dr. Connellhas been continuously funded by the NIH and other agencies since 1993and serves on numerous NIH study sections and review panels. She hasserved on a number of committees of the National Academy of Sciences,e.g., the Committee on Advances in Technology and the Prevention of theirApplication to Next Generation Biowarfare Agents (2004), Trends in Scienceand Technology Relevant to the Biological Weapons Convention; anInternational Workshop (2010), and the Committee to Review the ScientificApproaches used in the FBI's Investigation of the 2001 Bacillus anthracisMailings (2011). Current work is with The National Academies of Sciences“Education Institute on Responsible Science”, held in Jordan (2012),Malaysia (2013) and Trieste (2014).

Contact info:

Richard Russo973­972­1916russori@njms.rutgers.edu

Nancy Connell973­972­3759connell@njms.rutgers.edu

Location: Medical Sciences Building, Room A906; ICPH RBL