University of North Carolina at Chapel Hill
Departments of Microbiology & Immunology
Professor Immunology, Virology
1983 Meritorious Service Medal, United States Army 1989-90 Kenan Research Leave, The University of North Carolina at Chapel Hill 1996 Commissioner's Special Citation U.S. Food and Drug Administration 2003 National Associate National Academy of Sciences 2007 Bruce Witte Annual Lecturer Hepatitis B Foundation 2007 Fellow, American Association for the Advancement of Science 2009 John Enders Award for Contributions in Medical Virology Infectious Disease Society of America
My research focuses broadly on the molecular pathogenesis of acute and chronic hepatitis in humans due to hepatitis C virus (HCV) and hepatitis A virus (HAV). Our work thus lies at the interface of molecular virology, innate immunity, inflammation and disease pathogenesis. My primary interests include the molecular mechanisms by which these two hepatotropic viruses replicate their positive-strand RNA genomes, and how these viruses are recognized by host innate immune sensors. I am interested in learning how these viruses have evolved to evade innate antiviral defenses in the liver, and how these events influence the subsequent development of virus-specific adaptive immunity. Work in my laboratory has contributed to our understanding of how the HCV NS3/4A serine protease disrupts RIG-I and TLR3-mediated activation of IRF-3 and NF-?B, and how antiviral protease inhibitors counteract these effects. Recently, we have discovered that two distinct processing intermediates of the HAV 3Cpro cysteine protease, 3ABC and 3CD, similarly disrupt interferon signaling, and we are interested in determining how these viral evasion tactics relate to the disparate outcomes of these two intra-hepatic virus infections. A parallel focus in the laboratory has been the interaction of HCV with cellular tumor suppressor proteins, including in particular the retinoblastoma tumor suppressor Rb, and how such virus-host interactions contribute to cell cycle dysregulation and hepatocellular carcinogenesis in chronic hepatitis C. A related project focuses on the interaction of HCV with the liver specific microRNA miR-122, itself a tumor suppressor, and the mechanism underlying HCV dependence on miR-122 for efficient genome amplification.
Link to list of publications on PubMed.
University of North Carolina
Chapel Hill NC 27599-7080
(O)919 843 1848