Faculty & Staff Details
|Position:||Professor & Amarillo Community Endowed Chair|
|Bio||Dr. Ming-Hai Wang joined the TTUHSC School of Pharmacy in 2004 as a Professor of Biomedical Sciences. He also serves as the Amarillo Community Endowed Chair in Cancer Research and is currently the Director (interim) of the Cancer Biology Center of the School of Pharmacy. Dr. Wang received his medical degree (MD) from Zhejiang University School of Medicine (China) and his Ph.D from a joint program between Zhejiang University and the Medical University of Lübeck (Germany). Dr. Wang pursued postdoctoral training at the Borstel Research Center (Germany) and later at the National Cancer Institute of the NIH where he became a staff member in 1995. He went on to become an Assistant Professor at Wayne State University School of Medicine (Michigan). In 1999 he was appointed Associate Professor of Medicine and Cancer Biology at the University of Colorado School of Medicine (Colorado).
During his scientific career, Dr. Wang has received several awards from institutions and organizations such as the Federal Ministry for Science and Technology (Germany), the NIH Forgardy International Center (US), and the Cheung-Kong Scholars Endowment (China). He currently serves as an ad hoc reviewer for several biomedical journals including Carcinogenesis, Oncogene, Cancer Research, and Journal of Immunology. His research is supported by a R01 grant from the National Institutes Health and by the Amarillo Community Endowment of Texas.
Dr. Wang’s research is in the field of cancer therapy with molecular targeted approaches. The targeted therapy is an innovative strategy that destroys primary cancers and controls tumor metastasis. This approach employs humanized monoclonal antibodies or small chemical inhibitors that specifically block oncogenic kinase signaling leading to cancer apoptosis.
Specifically, Dr. Wang’s group has been working on a unique cancer cell marker known as the RON receptor tyrosine kinase. RON is abnormally present in various malignant epithelial cancers and promotes tumorigenic activities such as cellular proliferation, migration, invasion and distance metastasis. These features make RON an attractive drug target.
Dr. Wang’s laboratory has developed several strategies to produce biological agents for RON targeted cancer therapy. The first is to use inhibitory monoclonal antibodies to block RON-mediated oncogenic signals leading to inhibition of cancer growth. One of the candidate mAb has been characterized and is currently under intensive characterization including antibody humanization. The second is to use RON-specific anti-cancer immunoliposome for targeted cancer therapy. This is a molecular/pharmaceutical combined approach to design ‘smart’ drugs for delivery of cytotoxicity towards malignant epithelial cancers. The third approach is to apply molecular mRNA silencing techniques to block RON-mediated oncogenesis. Several prominent sequences specifically silencing RON expression has been obtained. By using viral delivery system, the effectiveness of RON siRNA in cancer treatment will be evaluated.
It is believed that these pharmaceutical cancer studies will advance our knowledge to validate RON as a molecular drug target for epithelial carcinogenesis. It will also provide the basis for the development of novel drugs for potential pharmaceutical application.
Wang, M.-H., Ronsin, C., Gesnel, M.-C., Coupey, L., Skeel, A., Leonard, E.J. and Breathnach, R. Identification of the RON gene product as the receptor for the human macrophage stimulating protein. Science. 1994, 266:117-119.
Wang, M.-H., Dlugosz, A.A., Sun, Y., Suda, T., Skeel, A., and Leonard, E.J. Macrophage stimulating protein induces proliferation and migration of murine keratinocytes. Exp. Cell Res. 1996, 226:29-46.
Wang, M.-H., Montero-Julian, F.A., and Leonard, E.J. Requirement of PI-3 kinase for epithelial cell migration activated by human macrophage stimulating protein. Oncogene. 1996, 13:2167-2175.
Wang, M.-H., Montero-Julian, F., Breathnach, R., Godowski, P.J., Takehara, T., Yoshikawa, W., Hagiya, M., and Leonard, E.J. Macrophage stimulating protein (MSP) binds to its receptor via the MSP ß chain. J. Biol. Chem. 1997, 272: 6999-17004.
Xiao, Z.-Q. Chen, Y.-Q., T. Suda, and Wang, M.-H. Replacement of two conserved tyrosine residues in the C-terminal Tail of the RON Receptor tyrosine kinase affects the morphology and motility of epithelial cells stimulated with macrophage stimulating protein. Biochem. Biophy. Res. Commu. 2000, 267:669-675.
Wang, M.-H., Fang, H.-L. and Chen Y.-Q. Identification of a novel splicing variant of the RON receptor tyrosine kinase in human colorectal carcinoma cell lines. Carcinogenesis 2000, 21: 1507-1512.
Chen, Y.-Q., Y.-Q., Zhou, Y.-Q., Angeloni-Andreazzoli, D., Kurtz, A.L., Qiang, X.-Z., and Wang, M.-H., Oveerexpression and activation of the receptor tyrosine kinase in a panel of human colorectal carcinoma cells lines. Exp. Cell Res. 2000, 261:229-238.
Chen, Y.-Q., Zhou, Y.-Q., Fisher, J.H., and Wang, M.-H. Targeted Expression of the receptor tyrosine kinase RON in distal lung epithelial cells results in multiple tumor formation: Oncogenic potential of RON in vivo. Oncogene 2002, 21:6382-6386.
Chen, Y.-Q., Zhou, Y.-Q., Fu, L.-H., Wang, D., and Wang, M.-H. Multiple Pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Carcinogenesis. 2002, 11:1811-1819.
Zhou, Y.-Q, Wang, D., Jiang, Y.-H., and Chen, Y.-Q., and Wang, M.H. Altered expression of the RON receptor tyrosine kinase in primary colorectal carcinomas: generation of different splicing variants and their biological significance. Oncogene 2003, 22:186-197.
Wang, M.-H., Wang, D., Shen, J.-F., and Chen, Y.-Q. Oncogennic and metastatic potentials of the RON receptor tyrosine kinase. Carcinogenesis. 2003, 23: 1291-1300.
Wang, D., Chen, U.-Q., and Wang, M.H. Collaborative activities of macrophage stimulating protein and transforming growth factor-ß1 in induction of epithelial to mesenchymal transition: role of the RON receptor tyrosine kinase. Oncogene, 2004, 23: 1668-1680.
Xu, X.-M, Wang, D., Shen, Q., Chen, Y.-Q., Wang, M.-H. RNA-mediated gene silencing of the RON receptor tyrosine kinase alters oncogenic phenotypes of human colorectal carcinoma cells. Oncogene. 2004, 23:8464-74.
Da Wang, Qi Shen, Xiang-Ming Xu, Yi-Qing Chen, and Ming-Hai Wang. Activation of the RON receptor tyrosine kinase attenuates transforming growth factor-beta1-induced apoptotic death and promotes phenotypic changes in mouse intestinal epithelial cells.
Carcinogenesis. 2005; 26:27-36.
Xu, X.-M. and M.-H., Wang. Mechanisms of cytoplasmic ß-catenin accumulation and its involvement in tumorigenic activities mediated by oncogenic splicing variant of the receptor originated from nantes tyrosine kinase. J. Biol. Chem. 2005, 280: 25087-25-94
Wang, MH, Yao, HP, and Zhou, YQ. Oncogenesis of the RON receptor tyrosine kinas: a molecular target for malignant epithelial cancers. Acta Pharmacol. Sinica, 2006, 27:641-650
Yao, HP, Luo, YL, Feng, L, Cheng, LF, Lu, Y, Wei, L, and Wang, MH. Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biology & Therapy. 2006, 5: 1179 – 1186
Wang M-H, Lao WF, Wang D, Luo Y-L, and Yao H-P. Blocking tumorigenic activities of colorectal cancer cells by a splicing variant of the RON receptor tyrosine kinase defective in the tyrosine kinase domain. Cancer Biology & Therapy, 2007, 6: 7
Lu, Y., Yao, H.P., and Wang, M.H. Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Cancer Lett. 2007, 257:157-64
Wang, M.H., Wei, L., Luo, Y.L., and Yao, H.P. Altered expression of the receptor tyrosine kinase in various epithelial cancers and its contribution to tumorigenic phenotypes in thyroid cancer cells. J. Pathol. 2007, (in press).