Francis V. Chisari
La Jolla, USA
Francis V. Chisari, M.D. is Emeritus Professor of Virology and Immunology at The Scripps Research Institute (TSRI), in La Jolla, California.
Between 1975 when he joined the TSRI faculty and his retirement in 2015, Dr. Chisari studied the host-virus interactions that determine the outcome of viral infections, using the hepatitis B (HBV) and hepatitis C (HCV) viruses as models. Along the way, he trained over 150 young scientists, including several who are leaders of the viral immunology scientific community today.
Dr. Chisari’s laboratory defined the kinetics, magnitude, specificity and function of the cytotoxic T lymphocyte (CTL) response to HBV and HCV in infected humans and chimpanzees; demonstrated the profoundly different capacity of these viruses to induce an innate immune response in the liver, established the immunological basis for viral clearance and disease pathogenesis during these infections, demonstrated that HBV persists for decades after recovery from acute viral hepatitis despite an ongoing CTL response, and discovered that virus-specific T cells and cells of the innate immune response secrete antiviral cytokines that inhibit the replication of HBV, HCV and other viruses in infected cells without killing them, forging a fundamental change in our understanding of the host-virus relationship. In collaboration with R. Brinster and R. Palmiter, he developed the first transgenic mouse models of a human viral pathogen (HBV), and his laboratory used these models to define the immunological basis of acute and chronic viral hepatitis, to discover the noncytolytic antiviral activity of the cytotoxic T cell response, to define the mechanism responsible for the “tolerogenic” effect of hepatocellular antigen presentation on antigen-specific T cell differentiation, and to demonstrate that chronic immune-mediated liver injury underlies the pathogenesis of liver cancer. His laboratory was among the first to use a robust cell culture based infection system for HCV, enabling his postdocs to discover: the structural heterogeneity of HCV particles, that autophagy pathway components are required to initiate HCV infection, that exosomes can mediate the spread of HCV to permissive cells (thereby avoiding antibody-mediated neutralization) and to nonpermissive cells such as plasmacytoid dendritic cells (thereby triggering interferon production), and that (paradoxically) HCV blunts the effector functions of that interferon response by activating a canonical antiviral host protein (PKR) that inhibits the translation of antiviral proteins in the infected cells.
In recognition of these contributions, Dr. Chisari has received many honors and awards including: the First Distinguished Scientific Achievement Award from the American Liver Foundation; the Distinguished Achievement Award from AASLD; the Distinguished Scientist Award from the Hepatitis B Foundation; the William H. Prusoff Lifetime Achievement Award from HEP DART; the Rous-Whipple Award from the American Society for Investigative Pathology, and the Distinguished Alumnus Award from Weill-Cornell University Medical College. In addition, Dr. Chisari has been elected to fellowship and membership in learned societies, including: the American Association for the Advancement of Science, the American Academy of Microbiology, the Association of American Physicians, the National Academy of Sciences, USA and the National Academy of Medicine, USA.