Area of Research: Hepatitis C virus (HCV) Dr. Grakoui joined the Emory Vaccine Center in the fall of 2004 as an Assistant Professor jointly appointed in the Departments of Medicine, Division of Infectious Diseases and Microbiology and Immunology at the Emory University School of Medicine. His laboratory is focused on understanding the host immune response to hepatitis C virus (HCV) in order to better facilitate vaccine development. Dr. Grakoui trained initially in molecular virology studying RNA replication and polyprotein processing of alphaviruses (Sindbis) and flaviviruses (yellow fever and HCV) before pursuing his PhD in immunology at Washington University in St.Louis. During his postdoctoral training as a Cancer Research Institute Postdoctoral Fellow at The Rockefeller University, Dr.Grakoui combined his two areas of interest, virology and immunology, to systematically dissect the role of HCV-specific effector lymphocytes in HCV infection. The goal of his lab is to understand the inextricable connectivity between HCV, the immune system, and consequent liver damage. Research Hepatitis C virus (HCV) infection is a growing public health problem affecting 170 million people worldwide (~3 million in the United States). While twenty percent of patients infected with HCV are able to clear the infection after several months, the majority of patients become chronic carriers who, in addition to being the source for most new infections, can progress to chronic active hepatitis with cirrhosis and/or hepatocellular carcinoma (HCC). These clinical sequelae of HCV infection now comprise the leading indication for liver transplantation in the United States and account for 8-10,000 deaths each year in the United States alone. Despite its grave clinical consequences (i) no vaccine exists to prevent HCV infection and (ii) the only licensed therapy (alpha interferon (IFN_), either alone or in combination with the nucleoside analog ribavirin) for chronic HCV infection is expensive, associated with poor response rates, and laden with significant side effects. The paucity of efficacious anti-HCV therapeutic options highlights the need for effective interventions aimed at augmenting or supplementing the natural immune response and that alone or in concert with drug therapy can prevent the detrimental consequences of HCV infection. Development of such successful intervention strategies requires a thorough understanding of the host determinants of infection resolution. Our previous work has established the importance of the memory CD4+ T cell response in HCV infection resolution and prevention of viral escape as well as confirmed the importance of intrahepatic CD8+ T cells in viral elimination. Our laboratory is now focused on four main project areas utilizing murine, human and non-human primate experimental systems:
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