Hepatitis C Virus (HCV) is a “silent stalker” in infected people, who can develop hepatocellular carcinomas (HCC) decades later. Our short-term goal is to study three areas:

(i) Host-pathogen interactions to identify the mechanism of HCV-associated HCC

(ii) Molecular virology of lymphotropic HCV in viral persistence and pathogenesis

(iii) Cancer biology in liver oncogenesis generated from tumor-initiating cells (TICs: “bad seeds” of treatment-resistant HCC) induced by interactions between environmental factors (alcohol, obesity) and HCV.

Our lab’s long-term goal is to test new therapeutic modalities for HCC in HCV-infected patients with alcoholism and/or obesity.

Our experience and resources on TICs have provided a unique opportunity to functionally dissect the alcohol-mediated self-renewal of liver TICs via TLR4 signaling. The p53 tumor suppressor acts as a barrier against stem cell proliferation, and inactivation of p53, or its stabilizing partner NUMB (cell fate decision molecule), leads to expansion of TICs. Although treatment efficacy of HCV has been dramatically improved in recent years, the incidence of HCV-associated HCC keeps rising due to the prevalence of obesity, alcoholism and illicit drug usage in HCV patients. Thus, we will continue our research on the development of new therapeutic modalities for HCC.