Arash Grakoui, PhD
Emory Vaccine Center
Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine
Yerkes National Primate Research Center
Emory Center for AIDS Research
Dr. Grakoui joined the Emory Vaccine Center in the fall of 2004 and is now an Associate 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.
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. 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 and human experimental systems:
- To understand the role of regulatory T cell populations and NK cells in facilitating HCV persistence and to define the functional and phenotypic differences between HCV-specific T effector cell populations in acute and chronic infection.
- To determine whether functional differences in HCV antigen presentation contribute to viral persistence.
- To define the impact of hepatic stellate cells and inhibitory ligands on anti-HCV immune responses.
- To determine the effect of various states of health including HIV co-infection, pregnancy, and following liver transplantation, on HCV pathogenesis.