Lab place: Medical college of NCKU 9F
Academic experience
- 1968 ~ 1972 ---- Bachelor of Science, National Taiwan University, ROC.
- 1972 ~ 1974 ---- Master degree, National Taiwan University, ROC.
- 1976 ~ 1980 ---- Ph. D, Ohio State University, USA.
- 1980 ~ 1983 ---- Research Fellow, Northwestern University, USA.
- 1983 ~ 1988 ---- Associate Professor, Department of Biochemistry & Molecular biology, Colloege of Medicin,
National Cheng Kung University
- 1988 ~ 2010 ---- Professor of Department of Biochemistry & Molecular biology,National Cheng Kung University
- 1989 ~ 1995 ---- Director of Department of Medical Technology, National Cheng Kung University
- 1996 ~ 1999 ---- Director of Department of Biochemistry & Molecular biology, National Cheng Kung University
- 2002 ~ present ---- Distinguished Professor of Department of Biochemistry & Molecular biology, National Cheng
Kung University
- 2010 ~ present ---- Chair Professor of Department of Biochemistry & Molecular biology, National Cheng Kung
University
Research Interest
Cardiovascular disease is still an important global health problem. Vascular Biology is the major research interest
in my lab. Thrombomodulin is a transmembrane protein in vascular endothelial cells and keratinocytes. It
can regulate blood coagulation by activating protein C, which in turn inhibits blood coagulation by inactivation
of factors Va and VIIIa. Thrombomodulin also plays an important role in cell-cell adhesion. It can regulate
the distribution of plasminogen and migration of endothelial cells. Recently we also demonstrated that it
can regulate inflammation responses by association with CD14 and monocyte adhesion to inflammatory endothelial
cells. We also interested in the role of thrombomodulin in wound healing and in vascular diseases including
atherosclerosis and aortic aneurysm using tissue specific gene knockout mice and recombinant proteins.
Expertise
VASCULAR BIOLOGY、HAEMOSTASIS AND FIBRINOLYSIS、BIOTECHNOLOGY
Selected Awards
The 54th Academic Award for Biology and Medical and Agronomy Sciences, Ministry of Education, Taiwan (2010)
The 10th Y.Z. HSU Scientific Award (2012)
The 16th National Chair Professorship Award, Ministry of Education, Taiwan (2013)
Selected Publications
Lai, C.-H., Wang, K.-C., Kuo, C.-H., Lee, F.-T., Cheng, C.-L., Chang, B.-I., Yang, Y.-J., Shi, G.-Y., Wu, H.-L.
(2017) Recombinant adeno-associated virus vector carrying the thrombomodulin lectin-like domain for the treatment
of abdominal aortic aneurysm. Atherosclerosis, 262 ,62-70.
Lin, W.-L., Chen, C.-C., Shi, G.-Y., Ma, C.-Y., Chang, C.-F. and Wu, H.-L. (2017). Monocytic thrombomodulin promotes
cell adhesion through interacting with its ligand, Lewisy. Immunology and Cell Biology, 95: 372–379.
Cheng, T.-L., Lai, C.-H., Shieh, S.-J., Jou, Y.-B., Yeh, J.-L., Yang, A.-L., Wang, Y.-H., Wang, C.-Z., Chen,
C.-H., Shi, G.-Y., Ho, M.-L., Wu, H.-L. (2016). Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis
and inflammatory bone loss. Sci Rep, 6:28340.
Hsu, Y.-Y., Shi, G.-Y., Wang, K.-C., Ma, C.-Y., Cheng, T.-L., Wu, H.-L. (2016). Thrombomodulin promotes focal
adhesion kinase activation and contributes to angiogenesis by binding to fibronectin. Oncotarget, 7:68122-68139.
Lai, C. –H., Wang, K. –C., Lee, F. –T., Tsai, H. –W., Ma, C. –Y., Cheng, T. –L., Chang, B. –I., Yang, Y. –J.,
Shi, G. –Y., and Wu, H. –L. (2016) Toll-like receptor 4 is essential in the development of abdominal aortic
aneurysm. PLoS One. 11:e0146565.
Wang, K. -C., Li, Y. -H., Shi, G. -Y., Tsai, H. -W., Luo, C. -Y., Cheng, M. -H., Ma C. -Y., Hsu, Y. -Y., Cheng,
T. -L., Chang B. -I., Lai, C. -H., and Wu, H. -L. (2015) Membrane-bound thrombomodulin regulates macrophage
inflammation in abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 35: 2412-2422.
Cheng, T. -L., Lai, C. -H., Chen, P. -K., Cho, C. -F., Hsu, Y. -Y., Wang, K. -C., Lin, W. -L., Chang, B. -I.,
Liu, S. -K., Wu, Y.-T., Hsu, C. -K., Shi, G. -Y., Wu, H. -L. (2015). Thrombomodulin promotes diabetic wound
healing by regulating toll-like receptor 4 expression. J Invest Dermatol, 135:1668-1675.
Huang, Y. -H., I, C. -C., Kuo, C. -H., Hsu, Y. -Y., Lee, F. -T., Shi, G. -Y., Tseng, S. -H., Wu, H. -L. (2015).
Thrombomodulin promotes corneal epithelial wound healing. PLoS One, 10:e0122491.
Kuo, C. -H., Chang, B. -I., Lee, F. -T., Chen, P. -K., Lee, J. -S., Shi, G. -Y., Wu, H. -L. (2015). Development
of recombinant AAV2/8 carrying kringle domains of human plasminogen for sustained expression and cancer therapy.
Hum Gene Ther, 26: 603-613.
Kuo, C. -H., Sung, M. -C., Chen, P. -K., Chang, B. -I., Lee, F. -T., Cho, C. -F., Hsieh, T. -T., Huang, Y. -C.,
Li, Y. -H., Shi, G. -Y., Luo, C. -Y., Wu, H. -L. (2015). FGFR1 mediates recombinant thrombomodulin domain-induced
angiogenesis. Cardiovasc Res, 105:107-117.
Lin, W. -L., Lin, Y. -S., Shi, G. -.Y, Chang, C. -F., Wu, H. -L. (2015). Lewis Y promotes migration of oral cancer
cells by glycosylation of epidermal growth factor receptor. PLoS One, 10:e0120162.
Ma, C.-Y., Chang, W.-E., Shi, G.-Y., Chang, B.-Y., Cheng, S.-E., Shih, Y.-T., and Wu, H.-L. (2015). Recombinant
thrombomodulin inhibits lipopolysaccharide-induced inflammatory response by blocking the functions of CD14.
J Immunol, 194:1905-1915.
Chao, T. –H., Tsai, W. –C., Chen, J. –Y., Liu, P. –Y., Chung, H. –C., Tseng, S. –Y., Kuo, C. –H., Shi, G. –Y.,
Wu, H. –L., Li, Y. -H. (2014). Cilostazol enhances mobilization and proliferation of endothelial progenitor
cells and collateral formation by modifying vasculo-angiogenic biomarkers in peripheral arterial disease.
Int J Cardiol, 172:e371-374.
Cheng, T. –L., Lai, C. –H., Jiang, S. –J., Hung, J. –H., Liu, S. –K., Chang, B. –I., Shi, G. –Y., Wu, H. –L.
(2014). RHBDL2 is a critical membrane protease for anoikis resistance in human malignant epithelial cells.
ScientificWorldJournal, 2014:902987-902995.
Cheng, T. –L., Wu, Y. –T., Lai, C. –H., Kao, Y. –C., Kuo, C. –H., Liu, S. –L., Hsu, Y. –Y., Chen, P. –K., Cho,
C. –F., Wang, K. –C., Lin, W. –L., Chang, B. –I., Chen C. –M., Hartmut Weiler, Shi, G. –Y., Wu, H. –L. (2013).
Thrombomodulin regulates keratinocyte differentiation and promotes wound healing. J Invest Dermatol, 133:1638-1645.
Lai, C. –H., Shi, G. –Y., Lee, F. –T., Kuo, C. –H., Cheng, T. –L., Chang, B. –I., Ma, C. –Y., Hsu, F. –C., Yang,
Y. –J., Wu, H. –L. (2013). Recombinant human thrombomodulin suppresses calcium chloride-induced abdominal
aortic aneurysms in mice. Ann Surg, 258:1103-1110.
Chen, P. –K., Chang, B. –I., Kuo, C. – H., Cheng, P. –S., Cho, C. –F., Chang, C. –F., Shi, G. –Y., Wu, H. –L.
(2013). Thrombomodulin functions as a plasminogen receptor to modulate angiogenesis. FASEB J, 27:4520-4531.
Lin, W. –L., Chang, C. –F., Shi, C. –S., Shi, G. –Y., Wu, H. –L. (2013). Recombinant lectin-like domain of thrombomodulin
suppresses vascular inflammation by reducing leukocyte recruitment via interacting with Lewis Y on endothelial
cells. Arterioscler Thromb Vasc Biol, 33:2366-2373.
Kuo, C. –H., Chen, P. –K., Chang, B. –I., Sung, M. –C., Shi, C. -S., Lee, J. –S., Chang, C. –F., Shi, G. –Y.,
Wu, H.-L. (2012). The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction
with Lewis Y antigen. Blood, 119:1302-1313.
Ma, C. –Y., Shi, G. –Y., Shi, C. -S., Kao, Y. –C., Lin, S. –W., Wu, H -L. (2012). Monocytic thrombomodulin triggers
LPS- and Gram-negative bacteria-induced inflammatory response. J Immunol, 188:6328-37.
Cheng, T. –L., Wu, Y. –T., Lin H. –Y., Hsu, F. –C., Chang, B. –I., Chen, W. –S., Lai. C. –H., Shi, G. –Y., and
Wu, H. –L. (2011). Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing. J Invest
Derm, 131:2486-2494.
Lai, C. -H., Luo, C. -Y., Lin, P. -Y., Kan, C. -D., Chang, R. -S., Wu, H. -L., Yang, Y. -J. (2011). Surgical
consideration of in situ prosthetic replacement for primary infected abdominal aortic aneurysms. Eur J Vasc
Endovasc Surg, 42:617-624.
Wei, H. -J., Li, Y. -H., Shi, G. -Y., Liu, S. -L., Chang, P. -C., Kuo, C. -H., and Wu,H. -L. (2011). Thrombomodulin
domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation. Cardiovasc
Res, 92:317-327.
He, R.-Y., Lin, C. –Y., Su, Y. –D., Chiu, K. –C., Chang, N. –S., Wu, H. –L., and Chen, S. –J. (2010). Imaging
live cell membranes via surface plasmon-enhanced fluorescence and phase microscopy. Opt Exp, 18:3649-3659.
Shi, C.-S., Shi, G.-Y., Hsiao, H.-M., Kao, Y.-C., Kuo, K.-L., Ma, C.-Y., Kuo, C.-H., Chang, B.-I., Chang, C.-F.,
Lin, C.-H., Wong, C.-H., and Wu, H.-L. (2008) Lectin-like domain of thrombomodulin binds to its specific
ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response. Blood. 112:3661-3670.
Shi, C.-S., Shi, G.-Y., Chang, Y.-S., Han, H.-S., Kuo, C.-H., Liu, C., Huang, H.-C., Chang, Y.-J., Chen, P.-S.,
and Wu, H.-L. (2005). Evidence of human thrombomodulin domain as a novel angiogenic factor. Circulation.
111:1627-1636.
Huang, H.-C., Shi, G.-Y., Jiang, S.-J., Shi, C.-S., Wu, C.-M., Yang, H.-Y., and Wu, H.-L. (2003). Thrombomodulin-mediated
cell adhesion: involvement of its lectin-like domain. J Biol Chem. 278:46750-46759.
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