Lorne Tyrrell

Biography

Professor, Dept. of Medical Microbiology & Immunology

Research Interest

The research in my laboratory is focused on the study of hepatitis B virus (HBV) and hepatitis C virus (HCV). We have a major interest in therapeutic approaches for the treatment of chronic viral hepatitis – either HBV or HCV. Our work on HBV has utilized the Pekin duck model to identify and verify nucleoside analogues with specific activity for hepadnaviruses (duck and human HBV). Our work has led to the licensing of the first oral antiviral for HBV – lamivudine – which is used worldwide. However, single nucleotide changes in the polymerase gene leads to lamivudine-resistant viruses; hence, newer agents that are less prone to resistance or the combination of antivirals to prevent resistance are additional approaches to therapy. Most recently we have focused on the covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. The cccDNA has a long half-life and is the source of viral reactivation when therapy with nucleoside analogues is stopped. Current work in the laboratory is examining ways to prevent reactivation using zinc finger proteins targeted to cccDNA. Our laboratory collaborated with Dr. Norm Kneteman’s laboratory to develop mice with chimeric human/mouse livers. These mice can be infected with either HBV or HCV. We have a particular interest in studying the innate immune response in the human hepatocytes in response to HCV infection of the chimeric mice. We believe the differences seen in the innate immune response may determine the outcome – persistence or clearance of HCV infection.