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專任教師

張鑫 教授

聯絡電話:02-2312-3456 轉 88290

E-mail: scchang093@ntu.edu.tw

個人資料

專長:

分子病毒學

學歷:

美國南加州大學生化所

經歷:

台大醫學院微生物學科教授 (2010.08~)
台大醫學院微生物學副教授 (1991.08-2010.07)
台大醫學院細菌學科客座副教授 (1990/02-1991/07)
美國加州理工學院生物學科研究員 (1988/10-1990/02)

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目前進行研究

We are interested in understanding the molecular mechanisms by which cellular factors and viral proteins are involved in the multiplication and pathogenesis of human hepatitis viruses and SARS coronavirus. 

        A. Molecular virology and pathogenesis of human hepatitis viruses.

Hepatitis C virus (HCV) possesses a positive single-stranded RNA genome that consists of a single open reading frame flanking by a highly conserved 5’ noncoding region and 3’ noncoding region.  Mechanisms involved in the replication of HCV are not fully understood.  Nevertheless, we have identified a specific interaction between the HCV NS5B RNA-dependent RNA polymerase and the 3’ coding region of the viral genome critical for HCV replication.   HCV infection often develops chronic liver diseases and is strongly associated with hepatocellular carcinoma.  The structural protein core and nonstructural proteins S3, NS4B, and NS5A have been indicated to have oncogenic potential, whereas NS4A is the cofactor of NS3 protease. Towards understanding the viral proteins and cellular factors involved in the oncogenesis of HCV, we have perform microarray analysis and GST pull-down assay and identified several cellular factors that are regulated by or associated with the viral proteins.  Biological significances of the cellular factors involved in the pathogenesis are currently under investigated.  On the other hand, hepatitis delta virus (HDV) may cause severe chronic hepatitis and fulminant hepatitis.  In collaboration with MF Chang (Department of Biochemistry and Molecular Biology), we have recently identified a novel nuclear export signal-interacting protein (NESI) critical for HDV ssembly. The molecular mechanism of NESI involved in the nuclear export and viral assembly are being examined. 

B. Molecular virology and pathogenesis of SARS coronavirus.

During the outbreak of SARS in 2003, we also joined the studies on SARS coronavirus.  In collaboration with MF Chang (Department of Biochemistry and Molecular Biology) and CL Kao (Department of Clinical Laboratory Science and Medical Biotechnology), we have completed the sequences of the whole genome of TW1 strain.  The viral structural proteins were successfully expressed in mammalian culture systems and a packaging signal required for the assembly of the viral RNA was determined.  We are currently working on understanding the molecular mechanisms involved in the viral assembly and pathogenesis.

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研究室成員

研究生:陳子翊、張池佑、戴于晴、陳昱欣、陳慧珈、張展華
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研究成果

1.Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C. Chang, Ming-Fu Chang* J Formos Med Assoc 2017. In Press. Single allele Lmbrd1 knockout results in cardiac hypertrophy.
2.Yu YTC, Chien SC, Chen IY, Lai CT, Tsay YG, Chang SC* (張鑫), Chang MF.* Surface vimentin is critical for the cell entry of SARS-CoV. J Biomed Sci. 2016 Jan 22;23:14.
3.Kuo YC, Chen IY, Chang SC (張鑫), Wu SC, Hung TM, Lee PH, Shimotohno K, Chang MF.* Hepatitis C virus NS5A protein enhances gluconeogenesis through upregulation of Akt-/JNK-PEPCK signalling pathways. Liver Int. 2014 Oct;34(9):1358-68.
4.Huang C, Jiang JY, Chang SC, Tsay YG, Chen MR, Chang MF. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen. J Virol. 2013 Feb;87(3):1596-604.
5.Tseng LT, Lin CL, Tzen KY, Chang SC, Chang MF. LMBD1 protein serves as a specific adaptor for insulin receptor internalization. J Biol Chem. 2013 Nov 8;288(45):32424-32.
6.Chen IY, Chang SC*, Wu HY, Yu TC, Wei WC, Lin S, Chien CL, Chang MF*. Upregulation of the chemokine (C-C motif) ligand 2 via a severe acute respiratory syndrome coronavirus spike-ACE2 signaling pathway. J Virol. 2010 Aug;84(15):7703-12.
7.Pan RY, Hung TM, Kou YH, Chan NL, Chang MF, Chang SC* In trans interaction of hepatitis C virus helicase domains mediates protease activity critical for internal NS3 cleavage and cell transformation. FEBS Lett. 2010 Feb 5;584(3):482-6.
8.Huang C, Chang SC, Yang HC, Chien CL, Chang MF. Clathrin-mediated post-Golgi membrane trafficking in the morphogenesis of hepatitis delta virus. J Virol. 2009 Dec;83(23):12314-24.
9.Hung TM, Chang SC, Yu WH, Wang YW, Huang C, Lu SC, Lee PH, Chang MF. A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis. Hepatology. 2009 Oct;50(4):1184-93
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