• Ph.D., Washington University in St. Louis, 1999
• B.A., Washington University in St. Louis, 1985

Research Interests: Hepatitis C virus (HCV) infection chronicity and its detrimental long-term sequelae now comprise the leading indication for liver transplantation in the United States. The paradoxical observation that HCV establishes a persistent infection despite the presence of humoral and cellular immune responses has provided the impetus to rigorously explore the host response to HCV. We are seeking to facilitate prophylactic and/or therapeutic vaccine development by defining the elements of the adaptive immune response critical for HCV resolution. The original hypothesis was that the acute or chronic outcome of HCV infection is determined by the sufficiency of the HCV-specific CD4+ T cell response. We recently published work utilizing the chimpanzee experimental model that unequivocally established for the first time the fundamental importance of the CD4+ T helper cell and CD8+ cytotoxic T cell in HCV infection resolution (Grakoui et al. 2003 Science; Shoukry et al. JExpMed 2003). These analyses showed that resolution of HCV infection requires intrinsic functional efficacy of the HCV-specific CD4+ T cell response and highlighted potential deficiencies in host responsiveness that may be targets for carefully designed immunotherapy. Together with information regarding the clinical outcome of each HCV infection, our laboratory is committed to the elucidation of the role that HCV-specific T cells play both in eliminating or maintaining viral replication and in potentiating or preventing cirrhosis and hepatocellular carcinoma. Careful examination of the concepts and hypotheses described here will bring us closer to understanding the inextricable connectivity between HCV, the immune system, and consequent liver damage.