Francis V. Chisari

American physician

Francis "Frank" Vincent Chisari (born 5 April 1942 in New York City)^[1] is a physician, experimental pathologist, and viral immunologist, known for his research on virus-host interactions and disease pathogenesis during hepatitis B and hepatitis C virus infections.^[2]

Education and career

Chisari graduated in 1963 with a bachelor's degree in biology magna cum laude from Fordham University and in 1968 with an M.D. from Weill Cornell Medical College. He was an intern in Internal Medicine at New York Hospital in 1968-1969, a fellow in anatomic pathology at the Mayo Clinic in 1069-1970, a staff associate in immunopathology at the NIH's Laboratory of Pathology in 1970-1972 . In 1973 he completed his residency in internal medicine at Dartmouth-Hitchcock Medical Center. At Scripps Research he was a postdoctoral research fellow from 1973-1975, then an assistant professor from 1975 to 1981, an associate professor from 1981 to 1988 during which he spent a sabbatical from 1983 to 1984 as a Fogarty Scholar in molecular biology at the Institut Pasteur^[3] and a full professor from 1988 until retiring as professor emeritus in 2015. During his tenure at Scripps he served as Associate Director and then Director of the NIH-funded General Clinical Research Center from 1984 to 2004 while also heading the Division of Experimental Pathology from 1988 to 2008 and the Laboratory of Experimental Virology from 2008 to 2015 funded entirely by NIH grants. He is now a consultant for a variety of nascent biotechnology companies and a scientific advisor for Vir Biotechnology.^[4]

Chisari studies the immunological basis for viral clearance and disease pathogenesis during persistent viral infections, especially HBV and HCV, the signaling pathways and effector molecules that mediate these antiviral effects, and the viral evasion strategies that subvert them. He is best known for demonstrating that chronic immune-mediated injury and inflammation can cause liver cancer and for discovering that antiviral T cells can purge viruses from infected cells noncytolytically by secreting antiviral cytokines that inhibit viral replication, thus controlling the infection while preserving the vital functions of the infected tissue.

Chisari's laboratory developed cell-based models and animal models of HBV and HCV infection and performed foundational studies elucidating the T-cell response to these viruses in infected humans, subhuman primates, and transgenic mice. His group discovered that cytotoxic T lymphocytes (CTL) secrete antiviral cytokiness that inhibit viral replication in the liver cell without killing the cell, thus controlling the infection while preserving the life-saving function of the liver, and establishing new paradigm in viral pathogenesis and immunobiology. His research informed novel immunotherapeutic approaches for the understanding, prevention and treatment of chronic HBV infection.^[5]

Chisari's laboratory also demonstrated that HCV RNA can be transmitted via exosomes from infected hepatocytes to uninfected hepatocytes while masked from detection by anti-HCV antibodies, identifying a unique mechanism for viral spread by escaping recognition by the immune response while in transit. They also demonstrated that exosomes released by infected cells can deliver HCV RNA to plasmacytoid dendritic cells, thereby triggering an innate host response that was subsequently shown to prevent viral spread to susceptible hepatocytes, establishing a new paradigm in hepatitis C virus biology.

Chisari has served on the editorial boards of numerous scientific journals. He holds many patents on the use of viral peptide epitopes for the treatment or prevention of hepatitis-B or hepatitis-C virus infections.^[6] In recognitions of his contributions, Chisari has received numerous honors and awards (listed below).

Awards and honors

1992 Elected Member, Association of American Physicians
1996 Elected Fellow, American Association for the Advancement of Science^[7]
1997 Jung Prize for Medicine, Jung Foundation for Science and Research
1999 Rous-Whipple Award, American Society for Investigative Pathology^[8]
1999 Distinguished Achievement Award, American Association for Study of Liver Disease^[9]
2002 Elected Fellow, the American Academy of Microbiology
2002 Elected Member, the National Academy of Sciences^[2]
2003 Elected Member, the National Academy of Medicine^[10]
2004 Distinguished Alumnus Award, Weill Cornell University Medical College
2007 Distinguished Scientist Award, Hepatitis B Foundation
2015 William H. Prusoff Lifetime Achievement Award
2017 First Distinguished Award in Hepatitis B Virus Research

Selected publications

Kapadia, S. B.; Chisari, F. V. (2005). "Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids". Proceedings of the National Academy of Sciences of the United States of America. 102 (7): 2561–6. Bibcode:2005PNAS..102.2561K. doi:10.1073/pnas.0409834102. PMC 549027. PMID 15699349.
Robek, M. D.; Boyd, B. S.; Chisari, F. V. (2005). "Lambda interferon inhibits hepatitis B and C virus replication". Journal of Virology. 79 (6): 3851–4. doi:10.1128/JVI.79.6.3851-3854.2005. PMC 1075734. PMID 15731279.
Gilbert, R. J.; Beales, L.; Blond, D.; Simon, M. N.; Lin, B. Y.; Chisari, F. V.; Stuart, D. I.; Rowlands, D. J. (2005). "Hepatitis B small surface antigen particles are octahedral". Proceedings of the National Academy of Sciences of the United States of America. 102 (41): 14783–8. Bibcode:2005PNAS..10214783G. doi:10.1073/pnas.0505062102. PMC 1253561. PMID 16203986.
Chisari, F. V. (2005). "Unscrambling hepatitis C virus-host interactions". Nature. 436 (7053): 930–2. Bibcode:2005Natur.436..930C. doi:10.1038/nature04076. PMID 16107831. S2CID 24837913. Cited in PMC
Wieland, S. F.; Chisari, F. V. (2005). "Stealth and cunning: Hepatitis B and hepatitis C viruses". Journal of Virology. 79 (15): 9369–80. doi:10.1128/JVI.79.15.9369-9380.2005. PMC 1181548. PMID 16014900. Free full text Cited in PMC
Wieland, S. F.; Eustaquio, A.; Whitten-Bauer, C.; Boyd, B.; Chisari, F. V. (2005). "Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids". Proceedings of the National Academy of Sciences of the United States of America. 102 (28): 9913–7. Bibcode:2005PNAS..102.9913W. doi:10.1073/pnas.0504273102. PMC 1175012. PMID 15994231.
Bukh, J.; Thimme, R.; Meunier, J. C.; Faulk, K.; Spangenberg, H. C.; Chang, K. M.; Satterfield, W.; Chisari, F. V.; Purcell, R. H. (2008). "Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain". Journal of Virology. 82 (16): 8183–95. doi:10.1128/JVI.00142-08. PMC 2519567. PMID 18550671.
Bobardt, M. D.; Cheng, G.; De Witte, L.; Selvarajah, S.; Chatterji, U.; Sanders-Beer, B. E.; Geijtenbeek, T. B.; Chisari, F. V.; Gallay, P. A. (2008). "Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus". Proceedings of the National Academy of Sciences of the United States of America. 105 (14): 5525–30. Bibcode:2008PNAS..105.5525B. doi:10.1073/pnas.0801388105. PMC 2291127. PMID 18378908.
Asabe, S.; Wieland, S. F.; Chattopadhyay, P. K.; Roederer, M.; Engle, R. E.; Purcell, R. H.; Chisari, F. V. (2009). "The size of the viral inoculum contributes to the outcome of hepatitis B virus infection". Journal of Virology. 83 (19): 9652–62. doi:10.1128/JVI.00867-09. PMC 2748002. PMID 19625407.
Takahashi, K.; Asabe, S.; Wieland, S.; Garaigorta, U.; Gastaminza, P.; Isogawa, M.; Chisari, F. V. (2010). "Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection". Proceedings of the National Academy of Sciences of the United States of America. 107 (16): 7431–6. doi:10.1073/pnas.1002301107. PMC 2867703. PMID 20231459.
Bissig, K. D.; Wieland, S. F.; Tran, P.; Isogawa, M.; Le, T. T.; Chisari, F. V.; Verma, I. M. (2010). "Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment". The Journal of Clinical Investigation. 120 (3): 924–30. doi:10.1172/JCI40094. PMC 2827952. PMID 20179355.
Gastaminza, P.; Whitten-Bauer, C.; Chisari, F. V. (2010). "Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection". Proceedings of the National Academy of Sciences of the United States of America. 107 (1): 291–6. Bibcode:2010PNAS..107..291G. doi:10.1073/pnas.0912966107. PMC 2806752. PMID 19995961.
Bandi, P.; Garcia, M. L.; Booth, C. J.; Chisari, F. V.; Robek, M. D. (2010). "Bortezomib inhibits hepatitis B virus replication in transgenic mice". Antimicrobial Agents and Chemotherapy. 54 (2): 749–56. doi:10.1128/AAC.01101-09. PMC 2812171. PMID 19949053.
Yang, P. L.; Althage, A.; Chung, J.; Maier, H.; Wieland, S.; Isogawa, M.; Chisari, F. V. (2010). "Immune effectors required for hepatitis B virus clearance". Proceedings of the National Academy of Sciences of the United States of America. 107 (2): 798–802. Bibcode:2010PNAS..107..798Y. doi:10.1073/pnas.0913498107. PMC 2818933. PMID 20080755.
Asabe, S.; Wieland, S. F.; Chattopadhyay, P. K.; Roederer, M.; Engle, R. E.; Purcell, R. H.; Chisari, F. V. (2009). "The size of the viral inoculum contributes to the outcome of hepatitis B virus infection". Journal of Virology. 83 (19): 9652–62. doi:10.1128/JVI.00867-09. PMC 2748002. PMID 19625407.
Chisari, F. V.; Isogawa, M.; Wieland, S. F. (2010). "Pathogenesis of hepatitis B virus infection". Pathologie-Biologie. 58 (4): 258–66. doi:10.1016/j.patbio.2009.11.001. PMC 2888709. PMID 20116937.
Dreux, M.; Chisari, F. V. (2011). "Impact of the autophagy machinery on hepatitis C virus infection". Viruses. 3 (8): 1342–57. doi:10.3390/v3081342. PMC 3185811. PMID 21994783.Chisari, F. V.; García-Sastre, A. (2011). "Pioneers of pathogenesis: Past and present". Current Opinion in Virology. 1 (3): 157–9. doi:10.1016/j.coviro.2011.06.006. PMID 22440715.
Guidotti, L. G.; Isogawa, M.; Chisari, F. V. (2015). "Host-virus interactions in hepatitis B virus infection". Current Opinion in Immunology. 36: 61–6. doi:10.1016/j.coi.2015.06.016. PMC 4593767. PMID 26186123.
Revill, P. A.; Chisari, F. V.; Block, J. M.; Dandri, M.; Gehring, A. J.; Guo, H.; Hu, J.; Kramvis, A.; Lampertico, P.; Janssen HLA; Levrero, M.; Li, W.; Liang, T. J.; Lim, S. G.; Lu, F.; Penicaud, M. C.; Tavis, J. E.; Thimme, R.; Members of the ICE-HBV Working Groups; ICE-HBV Stakeholders Group Chairs; ICE-HBV Senior Advisors; Zoulim, F. (2019). "A global scientific strategy to cure hepatitis B". The Lancet. Gastroenterology & Hepatology. 4 (7): 545–558. doi:10.1016/S2468-1253(19)30119-0. PMC 6732795. PMID 30981686.
Alter, H. J.; Chisari, F. V. (2019). "Is Elimination of Hepatitis B and C a Pipe Dream or Reality?". Gastroenterology. 156 (2): 294–296. doi:10.1053/j.gastro.2018.12.015. PMID 30593764.

References

^ biographical information from American Men and Women of Science, Thomson Gale 2004.
^ ^a ^b "Francis V. Chisari". National Academy of Sciences (nasonline.org).
^ "Frank Chisari, MD". Department of Immunology and Microbiology, Scripps Research.
^ "Francis V. Chisari, M.D." Vir Biotechnology (vir.bio).
^ "Rous-Whipple Award – 1999, Francis V. Chisari" (PDF). American Society for Investigative Pathology.
^ "Patents by Inventor Francis V. Chisari". Justia Patents (patents.justia.com).
^ "Historic Fellows Listing". American Association for the Advancement of Science.
^ Chisari, Francis V. (2000). "Viruses, Immunity, and Cancer: Lessons from Hepatitis B". The American Journal of Pathology. 156 (4): 1117–1132. doi:10.1016/S0002-9440(10)64980-2. ISSN 0002-9440. PMC 1876872. PMID 10751335.
^ "Distinguished Achievement Award Recipients". American Association for the Study of Liver Diseases (aasld.org).
^ "Chisari, Francis V., Member Directory". National Academy of Medicine.

Ohkoshi, S.; Hirono, K; Watanabe, K.; Hasegawa, K.; Yano, M. (2015). "Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis". World Journal of Hepatology. 7 (28): 2834–2840. doi:10.4254/wjh.v7.i28.2834. ISSN 1948-5182. PMC 4670955. PMID 26668695.