I am a clinician scientist who has worked for many years on T cell responses in chronic viral infections (EBV, HIV-1 and 2, HBV). Based in the Division of Infection and Immunity in the Windeyer Building, I now head a group of basic and clinical scientists all working on integrated aspects of the immunopathogenesis of chronic HBV infection. Our work uses samples from the viral hepatitis clinics that I do, and from our extensive clinical collaborations, to dissect out components of the immune response contributing to viral control versus liver damage. Key recent advances in our understanding of the T cell tolerance seen with HBV persistence have included the identification of Bim-mediated apoptosis as a mechanism of attrition of HBV-specific CD8, and the characterisation of defects attributable to the liver microenvironment that bias the effector function of CD8 cells. We are now investigating the degree to which the defective profile of these CD8 cells can be re-programmed by potent anti-viral therapy. Our work has also highlighted the potential of the large proportion of activated NK cells in the hepatic infiltrate to contribute to liver damage.
Our ultimate goal is to apply these insights to develop immunotherapeutic strategies that boost immune control of HBV with minimal liver damage, thereby allowing termination of long-term antiviral therapy and preventing the frequent outcomes of cirrhosis and hepatocellular carcinoma.