University of North Carolina at Chapel Hill
Dr. Lemon’s 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). His work thus lies at the interface of molecular virology, innate immunity, inflammation, and disease pathogenesis. Dr. Lemon’s 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. He is 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 Dr. Lemon’s laboratory has contributed to the 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, discovery has been made that two distinct processing intermediates of the HAV 3Cpro cysteine protease, 3ABC and 3CD, similarly disrupt interferon signaling, and there is interest in determining how these viral evasion tactics relate to the disparate outcomes of these two intra-hepatic virus infections. A parallel focus in his 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.