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Laboratory of Experimental Virology
Francis Chisari
Professor
Immunology and Microbial Science
TSRI - 1975
Education
M.D. Cornell University Medical College, 1968
Awards & Activities
Distinguished Advisory Committee, UCSD Cancer Center, 2000-present
Review Panel, Int'l Research Scholars Program, Howard Hughes Med. Inst., 2000-present
Scientific Advisory Board, Center for the Study of HCV, Rockefeller Univ., 2000-present
Board of Scientific Councilors, NIAID, NIH, 2001
Blue Ribbon Panel on Bioterrorism Research, NIAID, NIH, 2002
Expert Panel on Immunity and Biodefense, NIAID, NIH, 2002
Fellow, American Academy of Microbiology, 2002
Member, National Academy of Sciences, 2002
Member, Institute of Medicine, National Academy of Sciences, 2003
Distinguished Alumnus Award, Weill-Cornell University Medical College, 2004
Scientific Advisory Board, Northeast Biodefense Center, 2004-present.
Research Focus
Immunobiology and Pathogenesis of
Hepatitis B and C Virus Infection
The outcome of noncytolytic viral infections is largely determined by the cellular immune response. Our laboratory focusses on the host-virus interactions that determine the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Using a combination of real time viral dynamics and quantitative functional T cell analysis, we have demonstrated a direct relationship between viral clearance and the vigor, kinetics and homing potential of the antiviral T cell response to HBV and HCV, the rate with which they spread after inoculation and their ability to escape immune recognition. In addition, we have shown that there is a third effector limb in the immune response besides antibody neutralization and T cell-mediated destruction of infected cells: i.e. T cells also secrete antiviral cytokines that can purge viruses from infected cells without killing them. Currently we are applying genome-wide expression profiling to define the intracellular antiviral effector pathways that are triggered by these cytokines, and biochemical and molecular approaches to identify the points in the life cycles of these viruses that are interrupted by their antiviral effects.
Selected References
Guidotti, L.G., Rochford, R., Chung, J., Shapiro, M., Purcell, R. and Chisari, F.V. Viral clearance without destruction of infected cells during acute HBV infection. Science 284:825-829, 1999.
Guidotti, L.G., Chisari, F.V. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu. Rev. Immunol. 19:65-91, 2001.
Thimme, R., Oldach, D., Chang, K.M., Steiger, C., Ray, S., Chisari, F.V. Determinants of viral clearance and persistence during acute HCV infection. J. Exp. Med. 194:1395-1406, 2001.
Robek, M.D., Wieland, S.F., Chisari, F.V. Inhibition of hepatitis B virus replication by interferon requires proteasome activity. J. Virol. 76:3570-3574, 2002.
TSRI > IMS > Exp Vir
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