Hepatitis C Virus Pathogenesis Laboratory

Our research focuses on basic molecular virology and pathogenic mechanisms of hepatitis C virus (HCV). HCV is a single stranded RNA virus that belongs to the Flaviviridae family. Infection results in chronic liver disease in approximately 80% of individuals and over the course of 10-20 years of chronic insult to the liver results in extensive scaring of the liver (fibrosis and cirrhosis) and in some cases development of liver cancer (hepatocellular carcinoma, HCC). Unfortunately many of the molecular mechanisms involved in disease progression and carcinogenesis are unknown. In Australia there are approximately 220 000 infected individuals with an estimated 16 000 new cases each year, thus infection with HCV is a major burden to the health care system. Current therapy is effective in only 50% of individuals and there is no vaccine.

The primary goal of our research is to understand the hepatocyte response to HCV infection and how this relates to progression of liver disease. This is achieved using in vitro cell culture models for HCV replication and human HCV-infected liver samples. We have used DNA microarray technology to investigate differential gene expression profiles in normal and diseased liver and much of the ongoing work expands on these observations.  Current projects in my laboratory include:

• Understanding the role of the CXCR3 chemokine ligands in viral induced liver disease
• Identification and characterisation of novel interferon stimulated genes (ISGs) expressed in the HCV infected liver
• Characterisation of differential gene expression in HCC.  In particular we have identified osteopontin as significantly expressed in HCC and demonstrated that its over expression increases the growth rate hepatocytes both in vitro and in vivo.
• Characterise the interactions between HCV and alcohol metabolism, in particular the role of alcohol metabolsm on HCV replication and interferon signalling