Medicine / GI and Liver, Molecular Microbiology & Immunology, and Pathology
Keck School of Medicine
Innate immunology against viral infection
A major aspect of our research is devoted to understanding Hepatitis C Virus (HCV) in the view of innate immunology. About 80% cases of HCV infection establish chronic active hepatitis, leading patients to liver Cirrhosis, where the Scar tissue replaces healthy liver tissue with fibrous tissue. Cirrhosis is a condition which put the patient in risk of hepatocellular carcinoma (liver cancer) and end stage liver failure. Both conditions require liver transplantation. In fact, HCV-related liver diseases are the leading cause of liver transplantation in the US. Current therapy against HCV infection is Interferon (IFN) based treatment, in which many patients suffer from medication related toxicities. Plus, the success rate of current standard treatment is 40-50%, which is not satisfactory. Therefore, in my lab, we are focusing on the understanding of intra-hepatic innate immune response against hepatitis C virus with the aim to develop better therapeutic strategy. A second focus of our research is to unravel the complex mechanism caused by HCV infection and alcohol consumption to rapid progress of liver fibrosis to Cirrhosis. Alcoholism is also major cause of liver fibrosis to Cirrhosis. Clinically, It has been well recognized that the ethanol consumption in HCV infected patients synergistically exacerbates the liver fibrosis to Cirrhosis. Moreover, patients who consume EtOH exhibit resistance to IFN based anti HCV treatment. However, the molecular mechanism by which HCV and EtOH insult the liver tissue to promote the fibrosis through the activation of hepatic stellate cells. For this research goal, we have focused on understanding how HCV and alcohol metabolism promote the fibrosis through the investigation of cellular crosstalk between hepatocyte, macrophage, and hepatic stellate cells in the presence of HCV infection and EtOH. Through above described research program, Saito lab offers tremendous opportunity to learn cytokine, interferon biology, cell signaling, virology, and primary cell biology.