Faculty Profile, National Health Research Institutes, Taiwan

Faculty Profiles


Chungming Chang, Ph.D.

Distinguished Investigator
Institute of Molecular and Genomic Medicine
tonychang@nhri.org.tw

EDUCATION

- Ph.D., Dept. of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania (1970-1974)
- B.S., Dept. of Biology, Tunghai University, Taiwan, R.O.C. (1969)

PROFESSIONAL EXPERIENCES

- Distinguished Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan (2006-present)
- Chairman, Board of of Trustees, Fung-Chia University, Taiwan (2002-present)
- Director, National Science and Technology Program in Pharmaceutical and Biotechnology, National Science Council, Taiwan (2001-2003)
- Distinguished Investigator and Director, Department of Intramural Research Affairs, National Health Research Institutes, Taiwan (1997-2006)
- Dean, School of Life Sciences, National Yang-Ming University, Taiwan (1994-1995)
- Dean, Faculty of Physical Therapy, National Yang-Ming University, Taiwan (1993-1994)
- Director, Department of General Studies, National Yang-Ming University, Taiwan (1992-1993)
- Dean of Academic Affairs, National Yang-Ming University, Taiwan (1991-1996)
- Visiting Scientist, Department of Tumor Biology, Karolinska Institute, Sweden (1984-1985)
- Professor, Institute of Microbiology and Immunology, National Yang-Ming University, Taiwan (1981-present)
- Investigator, Laboratory of Tumor Biology, Dept. of Medical Research, Veterans General Hospital, Taiwan (1981-1997)
- Director, Graduate Institute of Microbiology and Immunology, National Yang-Ming Medical College, Taiwan (1981-1988)
- Associate Professor, Department of Microbiology, National Yang-Ming Medical College, Taiwan (1978-1981)
- Visiting Associate, National Cancer Institute, NIH, USA (1977-1978)
- Adjunct Assistant Professor, Department of Microbiology, School of Medicine, Temple University, USA (1977-1978)
- Forgarty Visiting Fellow, Laboratory of Cell Biology, NCI, NIH, USA (1974-1977)

RESEARCH INTERESTS

Chronic hepatitis B (CHB) is one of the most serious viral infections in humans worldwide. It is a highly risk factor for cirrhosis and hepatocellular carcinoma (HCC) and more than 350 million people in the world suffer from chronic HBV infection. Virus persistence in chronic HBV carriers relies on maintaining a pool of viral covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes, which presumably served as thetemplate for HBV gene expression. Apparently, cccDNA may play a pivotal role in the life cycle of HBV replication. To effectively control this disease, it will be important to characterize the regulatory mechanism of cccDNA-derived transcription and develop new drugs that can inhibit HBV replication during the progression of CHB. Recently, Dr. Chang has designed a strategy to examine the transcriptional activity of cccDNA by modifying the HBV genome with a BclI genetic marker. By using the RT-PCR/BclI digestion method, he found that the transcriptional activity of cccDNA is less efficiency as compared to the integrated genome. Furthermore, his results for the first time provide evidence that HBx is essential for the transcription of cccDNA.

By using a virion-producing cell line ES2, Dr. Chang also established a cell culture system that may accurately reflect the regulation of HBV replication in vivo. He demonstrated that TGF-b1can effectively inhibit HBV replication. With the treatment of TGF-b1 at physiological concentration, the level of viral replicative intermediates was dramatically decreased in both dividing cells and confluent cells. Concurrently, the levels of viral transcripts, core protein and nucleocapsid were significantly diminished after TGF-b1 treatment. His results indicated that TGF-b1 might exert its antiviral effect primarily through the transcriptional regulation. Interestingly, the inhibitory activity of TGF-b1 was associated with the preferential reduction in the level of pregenomic RNA (pgRNA) as compared to that of preC mRNA. Such regulatory process was quite different from those mechanisms induced by other cytokines. Taking together, it may imply that several mechanisms are involved in the inhibitory effect of elevated cytokines during chronic hepatitis progression and contributed synergistically to the control of HBV replication.

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Dr. Chang has been very active in academic activities in Taiwan and Asia Pacific region. He was elected as the Presendent of Chinese Immunologist Society (Taipei) and Chinese Cell Biology Society (Taipei). He is now serving as the Secretary General of APOCB (Asian-Pacific Cell Biology Society). Dr. Chang has authored more than 100 papers and hosted several international conference and symposia.

SELECTED PUBLICATIONS

1. Chou YC, Chen ML, Hu CP, Chen YL, Chong CL, Ysai YL, Liu TL, Jeng KS and Chang C*. Transforming growth factor-b1 suppresses Hepatitis B virus replication primarily through the transcriptional inhibition of pregenomic RNA. Hepatology 46:472-481, 2007. (*=Corresponding Author)

2. Chong CL, Huang SF, Hu CP, Chen YL, Chou HY, Chau GY, Shew JY, Tsai YL, Chen CT, Chang C* and Chen ML. Decreased expression of UK114 is related to the differentiation status of human hepatocellular carcinoma. Cancer Epidemiology Biomarkers and Prevention, 2007. (Accepted) (*=Corresponding Author)

3. Lin SJ, Chang C, Ng AK, Wang SH, Li JJ and Hu CP. Prevention of TGF-beta0induced apoptosis by interleukin-4 through Akt activation and p70S6K survival signaling pathways. Apoptosis 12(9):1659-1670, 2007.

4. Chou YC, Jeng KS, Chen ML, Liu HH, Liu TL, Chen YL, Liu YC, Hu CP and Chang C. Evaluation of hepatitis B virus transcriptional efficiency for covalently closed circular DNA by RT-PCR combined with restriction enzyme digestion method. J.Virol. 79(3) 1813-1823, 2005.

5. Lin SJ, Shu PY, Chang C, Ng AK and Hu CP. IL-4 suppresses the expression and the replication of hepatitis B virus in a hepatocellular carcinoma cell line Hep3B. J. Immunol. 171:4708-4716, 2003.

6. Ho TC, Jeng KS, Hu CP and Chang C*. Effects of genomic length on translocation of Hepatitis B virus polymerase-linked oligomer. J. Virol. 74:9010-9018, 2000. (*=Corresponding Author)

7. Huang HL, Jeng KS, Hu CP, Tsai CH, Lo SJ and Chang C*. Identification and characterization of a structural protein of hepatitis B virus: a polymerase and surface fusion protein encoded by a spliced RNA. Virology 275:398-410, 2000. (*=Corresponding Author)