Kyong-Mi Chang

faculty photo
Associate Professor of Medicine
Department: Medicine
Graduate Group Affiliations

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
Lab: (215) 823-5800 ext 6730
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 Clinical Expertise

Dr. Chang's clinical area of expertise is in the evaluation, treatment and study of patients with acute and chronic viral hepatitis B and C, with and without HIV coinfection. She established and directs the active GI/Liver clinic at the Philadelphia VA Medical Center to care for many veterans with acute and chronic liver diseases, while supervising GI fellows and rotating students/residents.

Description of Other Expertise

Dr. Chang is the Associate Chief of Research (ACOS/R&D) and Associate Dean for Research at the Philadelphia VA Medical Center, which is academically affiliated with the University of Pennsylvania. As such, Dr. Chang has the administrative oversight of VA-based and/or VA-funded research by VA/Penn dual-appointed Penn faculty at the Philadelphia VA Medical Center.

Selected Publications

Ghany M, Perrillo R, Li R, Belle SH, Janssen HL, Terrault NA, Shuhart MC, Lau DT, Kim WR, Fried MW, Sterling RK, Di Bisceglie AM, Han SH, Ganova-Raeva LM, Chang KM, Suk-Fong Lok A : Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and HBV Genotype. Clin Gastroenterol Hepatol July 2014.

Cho HS, M Kikuchi, Y Li, N Nakamoto, V Amorosa, ME Valiga, KM Chang: Induction of multiple immune regulatory pathways with differential impact in HCV/HIV coinfection. Frontiers in Immunology July 2014.

Bunchorntavakul C, Jones LM, Kikuchi M, Valiga ME, Kaplan DE, Nunes FA, Aytaman A, Reddy KR, KM Chang: Distinct Features in Natural History and Outcomes of Acute Hepatitis C. J. Clin. Gastroenterol Jan 2014.

Hafkin JS, MK Osborn, AR Localio, VK Amorosa, JR Kostmay, JJ Stern, P De La Torre, K Mounzer, I Frank, R Gross, K-M Chang, V. LoRe III: Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy. J. Viral Hepatitis Jul 2013.

Gardiner D, J Lalezari, E Lawitz, M DiMicco, R Ghalib, KR Reddy, KM Chang, M Sulkowski, J Anderson, B He, F McPhee, D Grasela, M Selby, A Korman and I Lowy: A randomized double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection. PLOS One May 2013.

Kluck J, RM O’Flynn, DE Kaplan and KM Chang: Evaluation of the significance of pretreatment liver biopsy and baseline mental health disorder diagnosis on hepatitis C treatment completion rates at a Veterans Affairs Medical Center. Hepatitis Research and Treatment 2013, May 2013.

Kim CW, K.M. Chang: Hepatitis C virus: virology and life cycle. Clinical and Molecular Hepatology 2013.

Aleksic M, N. Liddy, PE Molloy, N Pumphrey, A Vuidepot, KM Chang and BK Jacobsen: Different affinity windows for virus and cancer-specific T cell receptors: implications for therapeutic strategies. European Journal of Immunology Dec 2012.

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.

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Last updated: 12/03/2014
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