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Kyong-Mi Chang, M.D.

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
Associate Director, Penn Center for Viral Hepatitis, Hospital of University of Pennsylvania
Associate Chief of Staff for Research, Philadelphia VA Medical Center
Associate Dean for Research at the Philadelphia VA Medical Center, University of Pennsylvanina
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
A.B. (Chemistry, Mathematics, and Fine Arts)
Bryn Mawr College, 1983.
The Medical College of Pennsylvania, 1987.
Post-Graduate Training
General Surgery Internship, St. Francis Hospital/University of Connecticut, 1987-1988.
Family Practice Internship, Underwood Memorial Hospital/Thomas Jefferson University, Philadelphia, PA, 1988-1989.
Internal Medicine Residency, The Medical College of Pennsylvania, Philadelphia, PA, 1989-1992.
Gastroenterology Fellowship, Division of Gastroenterology, University of California at San Diego, 1992-1995.
NRSA Research Fellow (UCSD GI Division), Laboratory of Dr. Francis V Chisari, The Scripps Research Institute, La Jolla, CA, 1993-1995.
Research Associate/Sr Research Associate, Laboratory of Dr. Francis V Chisari, The Scripps Research Institute, La Jolla, CA, 1995-1999.
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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

Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS: Present and future therapies of hepatitis B: From discovery to cure. Hepatology Page: [Epub] August 2015.

Ogdie A, Pang WG, Forde KA, Samir BD, Mulugeta L, Chang KM, Kaplan DE, Amorosa VK, Kostman JR, Reddy RK, Schumacher RH, Lo Re V 3rd.: Prevalence and risk factors for patient-reported joint pain among patients with HIV/Hepatitis C coinfection, Hepatitis C monoinfection, and HIV monoinfection. BMC Musculoskelet Disord 16(93), April 2015.

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.

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Last updated: 09/29/2015
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