Stephen Polyak, PhD
Research Assistant Professor, Department of Laboratory Medicine

Chronic hepatitis C is a global disease, resulting in a spectrum of liver diseases. Unfortunately, therapeutic options for the infected patient are limited and are of limited efficacy. It is unclear how the virus causes liver disease and why some patients respond to therapy while others do not. The main focus of my research group is the interactions between human hepatocytes and hepatitis C virus (HCV). A major undertaking is to understand the interactions of HCV with liver cell innate antiviral and pro-inflammatory pathways. Previously we found that the HCV NS5A protein induces the expression of the pro-inflammatory chemokine, interleukin 8 (IL-8/CXCL8), which is associated with inhibition of the antiviral effects of interferon (IFN). One NIH funded project is looking at the molecular mechanisms of HCV protein induction of IL-8 and how IL-8 inhibits IFN. We are also focusing on the HCV capsid protein. Under an NIH Cooperative HCV Center grant, which includes collaborators at the University of Colorado and University of Virginia, we are studying innate antiviral and cellular immune responses in acutely infected patients, with particular emphasis on the HCV core protein. Most recently, we have established an NIH funded program to study the mechanism of action of botanical medicines that are frequently taken by patients with chronic hepatitis C. We have found that Silymarin, an extract from the Milk Thistle plant, inhibits in vitro HCV infection, antigen-specific and non-specific T cell proliferation, and NF-kB activation. Thus, Silymarin displays antiviral, immunmodulatory and anti-inflammatory effects. Our findings underscore the complex interactions of HCV with innate antiviral and pro-inflammatory defense pathways, which may affect HCV antiviral resistance and pathogenesis.