Kyong-Mi Chang, M.D.
Associate Professor of Medicine
Director, GI Hepatitis Clinic
Member, Abramson Cancer Center
Member, CAMB, Microbiology, Virology and Parasitology Program
Member, Center for AIDS Research
Staff Physician
Co-Director, Immunology Core
Director, GI Research
Co-Director, Immunology Program, NIH Center for Molecular Studies in Digestive & Liver Diseases
Liver Research Group
Viral Hepatitis Affinity Group
Department: Medicine
Graduate Group Affiliations
Contact information
A424, Medical Research Building
Philadelphia VA Medical Center
University and Woodland Ave
Philadelphia, PA 19104
Philadelphia VA Medical Center
University and Woodland Ave
Philadelphia, PA 19104
Office: (215) 823-5893
Fax: (215) 823-4394
Fax: (215) 823-4394
Email:
kmchang@mail.med.upenn.edu
kmchang@mail.med.upenn.edu
Publications
Links
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Primary Work Website
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Primary Work Website
Education
A.B. (Chemistry, Mathematics, and Fine Arts)
Bryn Mawr College, 1983.
M.D.
The Medical College of Pennsylvania, 1987.
A.B. (Chemistry, Mathematics, and Fine Arts)
Bryn Mawr College, 1983.
M.D.
The Medical College of Pennsylvania, 1987.
Post-Graduate Training
General Surgery Internship, St. Francis Hospital/University of Connecticut, 1987-1988.
Gastroenterology Research Fellowship, Laboratory of Dr. Francis Chisari, The Scripps Research Institute, University of California, San Diego, CA, 1993-1995.
GI Research Fellow/Research Associate, The Scripps Research Institute, La Jolla, CA, 1993-1997.
Gastroenterology Fellowship, Division of Gastroenterology, University of California at San Diego, 1992-1995.
Senior Research Associate, The Scripps Research Institute, La Jolla, CA, 1997-1999.
Internal Medicine Residency, The Medical College of Pennsylvania, Philadelphia, PA, 1989-1992.
Family Practice Internship, Underwood Memorial Hospital/Thomas Jefferson University, Philadelphia, PA, 1988-1989.
Permanent linkGeneral Surgery Internship, St. Francis Hospital/University of Connecticut, 1987-1988.
Gastroenterology Research Fellowship, Laboratory of Dr. Francis Chisari, The Scripps Research Institute, University of California, San Diego, CA, 1993-1995.
GI Research Fellow/Research Associate, The Scripps Research Institute, La Jolla, CA, 1993-1997.
Gastroenterology Fellowship, Division of Gastroenterology, University of California at San Diego, 1992-1995.
Senior Research Associate, The Scripps Research Institute, La Jolla, CA, 1997-1999.
Internal Medicine Residency, The Medical College of Pennsylvania, Philadelphia, PA, 1989-1992.
Family Practice Internship, Underwood Memorial Hospital/Thomas Jefferson University, Philadelphia, PA, 1988-1989.
Description of Research Expertise
Research InterestsThe 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.
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 addressing a number of hypotheses, including the following:
1. The outcome of HCV infection is determined by quantitatively and qualitatively distinct anviral T cell response. We are studying the relative frequency, repertoire, cytokine profile and activation level of HCV-specific CD4 and CD8 T cell response using both in vitro and ex vivo methods that allow determination of immunological hierarchy. In particular, we are examining the mechanisms whereby antiviral T cells are suppressed during chronic HCV infection. These studies will define the features of antiviral T response relevant in natural and therapeutic control of HCV.
2. Selection of T cell escape variants contribute to HCV persistence, disease progression and antiviral treatment resistance. HCV is a highly mutable virus that readily escapes recognition from neutralizing antibody. Based on the initial immunological analysis, we are looking for potential T cell escape variants to determine its prevalence and their effect in antiviral T cell response.
3. Alcohol and HIV accelerate the progression of HCV-associated liver disease by modulating the antiviral T cell response. The effect of these potential immunosuppressive factors in HCV-specific T cell response and the virus is currently being investigated.
We are also investigating the impact of various host and viral factors as well the interplay between the T cell subsets in HCV infection. It is hoped that the results of our study will be relevant in clinical care and vaccine development.
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:
Hyosun Cho, PhD, Postdoctoral Researcher
Geoffrey DuFrayne, Research Specialist
Nobuhiro Nakamoto, MD, PhD, Postdoctoral Researcher
Mary Valiga, RN, Research Coordinator
Selected Publications
Nakamoto, N, Kaplan, DE, Coleclough, J, Li, Y, Kaminski, M, Shaked, A, Olthoff, K, Gostick, E, Price, DA, Freeman, GJ, Wherry EJ, Chang KM : Functional restoration of HCV-specific CD8 T-cells by PD1 blockade is defined by their PD1 expression and compartmentalization. Gastroenterology 134(7): 1927-1937, Jun 2008Ebinuma H, Nakamoto N, Li Y, Price DA, Gostick E, Levine B, Tobias J, Kwok WW, Chang KM. : Identification and in-vitro expansion of functional antigen-specific CD25+FoxP3+ regulatory T-cells in hepatitis C virus infection. Journal of Virology 82(10): 5043-53, May 2008
Kaplan, DE, Ikeda, F, Li, Y, Nakamoto, N, Ganesan, S, Valiga, ME, Nunes, FA, Reddy, KR, Chang, KM: Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis. Journal of Hepatology 48(6): 903-13, Jun 2008.
Kaplan, DE, Nakamoto, N, Ganesan, S, Coleclough, J, Kaminski, M, Xin, D, Reddy, KR, Olthoff, K, Shaked, A, Chang, KM: Peripheral and intrahepatic T-cell recall antigen responses are associated with recurrent graft hepatitis in HCV-infected liver transplant recipients. The American Transplant Congress, San Francisco, CA May 2007.
Chang K.M: Regulatory T cells in hepatitis C virus infection. Hepatology Research 31: S309-S312, 2007.
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 132(2): 654-666, 2007.
Kaplan, DE, Nakamoto, N, Ganesan, S, Coleclough, J, Kaminski, M, Xiu, D, Shaked, A, Chang, KM: Regulatory and effector T cell responses in HCV-infected liver transplant recipients. The 57th Annual Meeting of the AASLD, Boston, MA October 2006.
Ebinuma, H, Li, Y, Chang, KM: In-vitro expansion and increased circulating frequency of Foxp3+CD4+CD25+ Tregs from patients with chronic hepatitis C virus infection. 2006 American Association of Immunologists Annual Meeting, Boston, MA May 2006.
Brau N., E.J. Bini , S Currie, H. Shen, W.N. Schmidt, P.D. King, S.B. Ho, R.C. Cheung, K.Q. Hu , B.S. Anand, F.R. Simon, A. Aytaman, D.P. Johnson, J.A. Awad, J. Ahmad, C.L .Mendenhall, M.C. Pedrosa, R.H. Moseley, C.H. Hagedorn, B. Waters, K.M. Chang, T.R. Morgan, S.J. Rossi, L.J. Jeffers, T.L. Wright, The VA-HCV-001 Study Group: Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin. Jounal of Viral Hepatology 13(4): 242-249, April 2006.
Kaplan D.E., K.M. Chang: Current Status of Vaccine Therapy for Hepatitis C Infection. Current Hepatitis Reports 5(2): 68-74, 2006.


