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, are of limited efficacy, difficult to tolerate, and expensive. 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 to understand interactions between human hepatocytes and hepatitis C virus (HCV) that lead to inflammation, a hallmark of HCV-induced liver disease. Previously we found that HCV infection induces expression of pro-inflammatory chemokines. Under an NIH Cooperative HCV Center grant, we are looking at the molecular mechanisms of how sensing of HCV infection by Pathogen Recognition Receptors (PRR) induces inflammatory chemokines that recruit immune cells to the infected liver. More recently, we have established an NIH funded program to study the mechanism of action of botanical medicines that are commonly taken by patients with chronic hepatitis C. We have found that silymarin, an extract from the Milk Thistle plant, inhibits HCV infection, T cell proliferation and inflammatory cytokine expression, and NF-kB activation. Thus, silymarin displays antiviral, immunmodulatory and anti-inflammatory effects. In summary, defining the complex interactions of HCV with innate antiviral and pro-inflammatory cellular defense pathways has revealed opportunities for complementary and alternative medicine-based approaches for treatment of hepatitis virus infection, hepatic inflammation and liver disease. Ultimately, we hope to develop natural product-derived novel medicines for liver disease of both viral and non-viral etiologies.