Kyong-Mi Chang MD
Assistant Professor, Dept of Medicine, Gastroenterology Division

Microbiology, Virology and Parasitology Program

Gene Therapy and Vaccines Program

Address

A212, Medical Research
Philadelphia VA Medical Center
Philadelphia, PA 19104

Office tel.: 215 823-5893
Lab tel.: 215 823-5800 ext 6730/6726
Fax: 215 823-4394
E-mail: kmchang@mail.med.upenn.edu

Link(s)

Dr. Chang's Gastroenterology Page


Education

Bryn Mawr College: BS (Chemistry), 1983.

Medical College of Pennsylvania: MD (Medicine), 1987.

Medical College of Pennsylvania: Residency (Internal Medicine), 1992.

University of California: Fellowship (Gastroenterology, Hepatology), 1995.

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), an RNA virus with high rate of persistence (50-80%) associated with chronic necroinflammatory liver disease that can progress to liver cirrhosis and hepatocellular carcinoma.

Key words: HCV immune pathogenesis, HCV persistence, Viral escape, Viral persistence, Epitope mapping, Liver disease, T cell suppression, HIV/HCV coinfection, Alcohol.

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Description of Research

Our research focuses on the immune pathogenesis of human HCV infection, testing the hypothesis that antiviral T cells play an important role in the outcome of HCV infection and identifying the relevant immunological features of successful HCV clearance or liver disease progression. In the absence of convenient animal model of HCV, we have identified 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 patient samples in various in-vitro and ex-vivo T cell assays, we are defining the role of effector and regulatory T cells in HCV infection and liver disease progression. In particular, we are studying the role of CD4+CD25+ regulatory T cells and immunoregulatory cytokines in HCV persistence. Moreover, we have begun to examine if specific HCV gene products may induce regulatory T cells. Finally, with the combined use of clinical, epidemiological, immunological and immunogenetic studies, we are examining if various environmental, host and viral determinants of HCV pathogenesis and treatment response (e.g. alcohol, HIV-coinfection, HLA type, viral genotype and sequence variation) may mediate influence the outcome of HCV infection through T cells. The long term goal of our studies is to understand the immune mechanism of HCV pathogenesis and to help develop therapeutic approaches to prevent chronic infection and liver disease progression to cirrhosis and liver cancer.

Recent Publications

1. Sugimoto, K, D.E. Kaplan, F. Ikeda, J. Ding, J. Schwartz, F.A. Nunes, H.J. Alter and K.M. Chang. Strain-specific T cell suppression and protective immunity in patients with chronic HCV infection. J. Virol. 2005; 79 (11): 6976-6983.
2. Kaplan D.E., K. Sugimoto, F. Ikeda, J. Stadanlick, M. Valiga, K. Shetty, K.R. Reddy and K.M. Chang. Virus-specific and non-specific T cell response relative to ethnicity, genotype and outcome during antiviral therapy for chronic HCV infection. Hepatology 2005; 41: 1365-1375.
3. Bini E.J., N. Bräu, S. Currie H. Shen, B.S. Anand, K.Q. Hu, L. Jeffers, S.B. Ho, D. Johnson, W.N. Schmidt, P. King, R. Cheung, T. R. Morgan, J. Awad, M. Pedrosa, K.M. Chang, A. Aytaman, F. Simon, C. Hagedorn, R. Moseley, J. Ahmad, C. Mendenhall, B. Waters, D. Strader, A.W. Sasaki, S. Rossi, T. L. Wright. Prospective Multicenter Study of Eligibility for Antiviral Therapy Among 4,084 U.S. Veterans with Chronic Hepatitis C Virus Infection. Am J Gastroenterol 2005;100:1–8.
4. Merriman N.A., S.B. Porter, C.M. Brensinger, K.R. Reddy, K.M. Chang. Racial difference in mortality among U.S. veterans with HCV/HIV coinfection. Am J Gastroenterol 2006: 101 (4): 760-767.
5. Kaplan D.E., K. Sugimoto, K. Newton, M.E. Valiga, F. Ikeda, A. Aytaman, F.A. Nunes, M.R. Lucey, B.A. Vance, R. Vonderheide, K.R. Reddy, J. McKeating, K.M. Chang. Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology 2007: 132 (2): 654-66.

Lab

Rotation Projects

1. Effector T cell dysfunction in HCV persistence
2. Functional analysis and expansion of effector T cells in HCV infection
3. Identification of T cell epitopes using overlapping peptide library
4. Immunoregulatory factors in HCV persistence
5. Role of HCV gene products in regulatory T cells and effector T cell dysfunction
6. HCV-specific T cells in viral clearance and persistence
7. T cell escape mutation in patients with acute and chronic hepatitis C
8. Analysis of intrahepatic T cell response in HCV-infected patients
9. T cell response in patients undergoing antiviral therapy for chronic HCV infection
10. HCV immunogenetics

Lab personnel:

David Kaplan MD, Assistant Professor of Medicine
Nobuhiro Nakamoto MD PhD, Postdoctoral Fellow
Yun Li PhD, Senior Research Investigator
Diana Lim, Research Specialist
Mary Valiga R.N., Research Coordinator
Becky Harris, Undergraduate Student