HCV PATHOGENESIS
HCV is a very successful pathogen infecting over 170 million people worldwide. Chronic HCV infection is established in over 85% of cases, and approximately 70% of these individuals develop cirrhosis or hepatocellular carcinoma. There is currently no vaccine and many strains are resistant to the drugs in use. Understanding how HCV evades the antiviral response will contribute towards the development of improved treatment strategies. This is the focus of one of the research projects in my laboratory. One of the tools HCV uses against the cell is a virally encoded signal transduction modulator protein NS5A, which binds to dsRNA-dependent protein kinase (PKR) and inhibits its activation. This prevents the expression of cytokines like Interferon-beta (IFN-beta), which is required to induce the antiviral state in the infected organism. This allows the virus to persist in the infected cells of the liver.

An essential part of the antiviral response is induction of apoptosis in the infected cell. NS5A expression significantly decreases cellular sensitivity to the apoptosis-inducing drug Etoposide. The second focus of research in our laboratory is to understand the connection, if any, between the inhibition of apoptosis in the infected cell and the development of hepatocellular carcinoma.

A third project involves the identification of drugs that can inhibit NS5A. To do this we are using the promoter of the IFN-beta gene linked to the coding sequence of the enhanced green fluorescence protein (eGFP) gene. We are using the expression of eGFP following viral infection to test plant extracts for inhibitory activity against NS5A.

TISSUE ENGINEERING
In collaboration with Dr. Jeffrey Coffer of the TCU Chemistry Department, we are growing mouse stromal cells on a scaffold made up of Poly-caprolactone (PCL) and a modified form of silicon (BioSilicon). These MSCs are capable of differentiating into osteoblasts as evidenced by the appearance of markers specific to this cell type. The long-term goal is to test the ability of the system to induce bone growth and repair.