Kyong-Mi Chang

faculty photo
Associate Professor of Medicine
Member, Abramson Cancer Center, University of Pennsylvania
Member, CAMB, Microbiology, Virology and Parasitology Program, University of Pennsylvania
Member, Center for AIDS Research, University of Pennsylvania
Co-Director, Immunology Program, NIH Center for Molecular Studies in Digestive & Liver Diseases, University of Pennsylvania
Viral Hepatitis Affinity Group, University of Pennsylvania
Associate Director, Penn Center for Viral Hepatitis, Hospital of University of Pennsylvania
Department: Medicine

Contact information
A424, Medical Research Building
Philadelphia VA Medical Center
University and Woodland Ave
Philadelphia, PA 19104
Office: (215) 823-5893
Fax: (215) 823-4394
Graduate Group Affiliations
Education:
A.B. (Chemistry, Mathematics, and Fine Arts)
Bryn Mawr College, 1983.
M.D.
The Medical College of Pennsylvania, 1987.
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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:

Jang-June Park PhD, research associate
Xiawang Qu PhD, postdoctoral researcher
Keisuke Ojiro MD PhD, postdoctoral researcher
James Keith, research specialist
Danielle Levine, research specialist
Mary Valiga RN, research coordinator

Description of Itmat Expertise

Dr. Chang is engaged in translational research using patient samples to examine T cell immune pathogenesis in the outcome and treatment of hepatitis B and hepatitis C virus infection. She has also organized a highly translational group of investigators on campus interested in viral hepatitis (the Viral Hepatitis Affnity Group) that convenes for monthly Penn Center for Viral Hepatitis Lab Meetings.

Selected Publications

31. Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA, Kunisawa J, Shibata N, Grunberg S, Sinha R, Zahm AM, Tardif MR, Sathaliyawala T, Kubota M, Farber DL, Collman RG, Shaked A, Fouser LA, Weiner DB, Tessier PA, Friedman JR, Kiyono H, Bushman FD, Chang KM, Artis D. : Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336(6086): 1321-1325, June 2012.

Doi H, TK Iyer, E Carpenter, H Li, KM Chang, RH Vonderheide, DE Kaplan: Dysfunctional B-cell activation in cirrhosis due to hepatitis C infection associated with disappearance of CD27+ B-cell population. Hepatology 55(3): 709-719, March 2012.

20. Shoukry N.H., S. Pelletier, K.M. Chang. : Editorial: A View to Natural Killer Cells in Hepatitis C. Gastroenterology 141(4): 1144-1148, October 2011.

Chang, K.M.: Hepatitis B and the Immune System. In: Current Hepatitis Reports 9(4), 2011.

Chang, K.M.: Immune Pathogenesis of Viral Hepatitis B and C. In: Zakim and Boyer Text Book of Hepatology, 6th Edition. Elsevier, Page: 118-128, 2011.

17. Chang, K.M: Hepatitis B Immunology for Clinicians. In: Clinics in Liver Disease 2010 14(3): 409-424, August 2010.

29. Wang GP, SA Sherrill-Mix, KM Chang, C Quince and FD Bushman: HCV Transmission Bottlenecks Analyzed by Deep Sequencing. J. Virology 84(12): 6218-6228, July 2010.

Rech AJ, Mick R, Kaplan DE, Chang KM, Domchek SM, Vonderheide RH.: Homeostasis of peripheral FoxP3(+) CD4 (+) regulatory T cells in patients with early and late stage breast cancer. Cancer Immunol Immunother 59(4): 599-607, April 2010.

Billerbeck E., N. Nakamoto, B. Seigel, H.E. Blum, K.M. Chang, R. Thimme. : Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic HCV infection. Journal of General Virology 90(7): 16920701, July 2009.

41. Carpenter E.L., R. Mick, A.J. Rech, G.L. Beatty, T.A. Colligon, M.R. Rosenfeld, K.M. Chang, D.E. Kaplan, S.M. Domchek, P.A. Kanetsky, L.A. Fecher, K.T. Flaherty, L.M. Schuchter, R.H. Vonderheide. : Collapse of the CD27+ B cell compartment associated with systemic plasmacytosis in patients with advanced melanoma and other cancers. Clinical Cancer Research 15(13): 4277-87, July 2009.

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Last updated: 06/22/2012
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