Description of Research Expertise

Research Interests
The main interest of our translational research laboratory is the immune mechanisms of viral persistence and liver disease progression in patients infected with hepatitis C virus (HCV) and hepatitis B virus (HBV), both hepatotropic viruses that can cause chronic necroinflammatory liver disease with progression to liver cirrhosis and hepatocellular carcinoma.

As the Immunology Center for the NIDDK-sponsored Hepatitis B Virus Clinical Research Network (http://www.hepbnet.org/default_content.asp), we are studying immune responses in HBV-infected patients at various stages of disease and therapy from various clinical centers throughout North America.


Key words: HCV, HBV, liver disease, HIV/HCV coinfection, alcohol, viral pathogenesis, viral persistence, immune regulation, T cell exhaustion, transplant tolerance, epitope mapping, immunogenetics

Description of Research
Our research focuses on the immune pathogenesis of human HCV and HBV infection, testing the hypothesis that antiviral T cells play an important role in the outcome of viral hepatitis and identifying the relevant immunological features of successful viral clearance, therapy or liver disease progression. In the absence of convenient animal models, we are studying valuable cohorts of persons with distinct clinical and virological outcome (e.g. acute, resolved, chronic infection with varying degrees of liver disease and treatment stage) using various in-vitro and ex-vivo T cell assays to define the immunological determinants in the outcome of HCV and HBV infection. In particular, we are examining:

1. Mechanism of effector T cell dysfunction in HCV and HBV infection
- Intrinsic costimulatory pathways (PD-1, CTLA-4)
- Indirect regulation through immune regulatory T cells
- Viral escape mutation

2. Role of T cells in the outcome of HCV and HBV infection
-in acute, chronic and resolved infection
-in the setting of HIV coinfection
-prognosticating therapeutic outcome
-in liver disease progression

3. Virus-specific immune response in peripheral blood and the liver compartments, using samples obtained from patients undergoing liver biopsy, resection or explantation.

4. Relevance of various host, viral, environmental or demographic factors in HCV and HBV infection (e.g. alcohol, HIV/HBV/HCV coinfections, immunogenetics, race and liver transplantation).

5. HCV replication in vitro using permissive human hepatoma cell lines


These studies are relevant in understanding viral hepatitis pathogenesis with potential contribution towards improved clinical care and vaccine development.


Rotation Projects
1. Multi-color FACS analysis to examine Tregs and T cell phenotype in human HBV or HCV infection.
2. Immune costimulatory pathways (PD-1, CTLA4) in T cell dysfunction in HCV and HBV infection
3. Identification of T cell epitopes and antigenic hierarchy using overlapping peptide libraries
4. Effector and Regulatory T cell response in acute hepatitis C with and without HIV coinfection
5. Immune tolerance mechanisms in HCV-infected liver transplant recipients
6. Immune regulation and restoration in virus-infected liver.
7. HCV infection, replication and immune regulation in vitro using cell culture system
8. HCV immunogenetics


Lab personnel:
Hyosun Cho PhD, postdoctoral researcher
Mitra M. Eghbal B.S., research specialist
Masahiro Kikuchi MD PhD, postdoctoral researcher
Chang-Wook Kim MD, postdoctoral researcher
Keith W. Torrey B.A., research specialist
Mary E. Valiga R.N., research coordinator
Raluca Vrabie MD, postdoctoral researcher