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Hwa-Chain Robert Wang College of Veterinary Medicine |
Keywords:
Oncogenes, Signal Transduction, Cellular Transformation,
Apoptosis, Cell Quiescence, Cancer, Anticancer
Research Area:
My primary research interest is to uncover novel signaling pathways which may cross-link cellular transformation to cell quiescence or apoptosis. Ultimately, I expect to apply the understanding of intracellular signaling controls to anticancer treatment and prevention by selective induction of apoptotic signaling pathways in transformed cells or restoration of signaling control to re-gain the control of cell growth.
Description of Research:
My research interests are to pursue novel molecules functioning in a quiescent state of normal cells and in apoptosis of malignantly transformed cells and to build translational research as a bridge from basic research to clinical research and applications for anticancer therapeutics and prevention. The goal of my basic research is to have a better understanding of the control of human cancers through exploration of novel signaling pathways for regulating cellular transformation, quiescence, and apoptosis. The approach of my translational research is to build preclinical models that reflect the molecular basis of cancer etiology and progression and for studies of tumor biology and etiology. Through molecular classification of oncogene- or carcinogen-induced human cancer cells, the genetic and molecular changes will be utilized as elements to constitute unique, identifiable characteristics of signatures of precancerous and cancerous cells at all stages of cancer development. Based on the molecular signature of cancerous cells, we will be able to determine the stage of cancers and identify molecular targets for choosing agents that prevent cancer by interfering with the biological processes underlying cancer development. Through collaborations we expect to establish research programs with multi-disciplines to link basic molecular and cellular research to clinical studies that will benefit our society for anticancer prevention and treatment.
Current Projects: (1) Identifying the role of a new family of protein kinase SAMK/Krs (src-activated MBP kinase/kinase responsive to stress) and Krs1-derived kinases in modulating cell quiescence and apoptosis. (2) Identifying the proapoptotic role of oncogenic Ras in the selective apoptosis of cancerous cells induced by discriminating anticancer agents. (3) Determining the potency and molecular signatures of tobacco carcinogens in the development of human breast cancer cells.
Selected Publications (of 46):
- Song, P., Wei, J., and Wang, H-C.R. 2005. Distinct roles of the ERK pathway in modulating apoptosis of Ras-transformed and non-transformed cells induced by anticancer agent FR901228. FEBS Letters: 579:90-94
- Song, P., Wei, J., Plummer III, H., and Wang, H-C.R. 2004. Potentiated caspase-3 in ras-transformed 10T1/2 cells. Biochemical and Biophysical Research Communications 322:557-564.
- Song, P. and Wang, H-C.R. 2004. Efficient Identification of TetR-Expressed Cell Lines for Tetracycline-Regulated Gene Expression. Electronic Journal of Biotechnology 7(2): 195-198.
- Wang, H-C.R. 2003. The role of Krs1 in cell cycle arrest. Drug News and Perspectives 16(10), 663-668.
- Wang, H-C.R. and Parsons, J.T. 1989. Deletions and insertions within an amino terminal domain of pp60v-src inactivate transformation and modulate membrane stability. Journal of Virology 63:291-302.
- Reynolds, A.B., Kanner, S.B., Wang, H-C.R., and Parsons, J.T. 1990. Stable association of activated pp60src with two tyrosine-phosphorylated cellular proteins. Molecular and Cell Biology 9:3951-3958.
- Bouton, A.H., Kanner, S.B., Vines, R.R., Wang, H-C.R., Gibbs, J.B., and Parsons, J.T. 1991. Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine phosphorylated cellular proteins with GTPase activating protein. Molecular and Cell Biology 11:945-953.
- Kanner, S.B., Reynolds, A.B., Wang, H-C.R., Vines, R.R., and Parsons, J.T. 1991. The SH2 and SH3 domains of pp60src direct stable association with tyrosine-phosphorylated proteins p130 and p110. EMBO. Journal 10:1689-98.
- Wang, H-C.R. and Erikson, R.L. 1992. Activation of protein serine/threonine kinases p42, p63 and p87 in Rous sarcoma virus-transformed cells: Signal transduction/Transformation-dependent MBP kinases. Molecular Biology of Cell 3:1329-1337.
- Wang, H-C.R. 1996. Induction of down-regulation of the kinase activities of Mek, p42Erk, p90RSK, and p63SAMK in chicken embryo fibroblast at the late stage of src-induced cellular transformation. Journal of Cellular Physiology 168:87-96.
- Taylor, L., Wang, H-C.R., and Erikson, R.L. 1996. Newly identified stress-responsive protein kinases KRS-1 and KRS-2. Proceedings of the National Academy of Sciences USA 93:10099-10104.
- Shidaifat, F., Canatan, H., Kulp, S., Sugimoto, Y., Zhang, Y., Brueggemeier, R.W., Somers, W.J., Chang, W.Y., Wang, H-C.R., and Lin, Y.C. 1997. Gossypol arrests human benign prostatic hyperplastic cell growth at G0/G1 phase of the cell cycle. Anticancer Research 17:1003-1010.
- Mehta, V., Connors, L., Wang, H-C.R., and Chiu, I.M. 1998. Fibroblast variants nonresponsive to FGF-1 are defective in its nuclear translocation. Journal of Biological Chemistry 273:4197-4205.
- Rajgolikar, G, Chan, K.K., and Wang, H-C.R. 1998. Effects of a novel antitumor depsipeptide FR901288 on human breast cancer cells. Breast Cancer Research and Treatment 51:29-38.
- Wang, H-C.R. 1999. FR901228, Antineoplastic antibiotic. Drug of the Future 24:1184-1188.
- Wang, H-C.R. 2000. Recovery of protein kinases from renatured SDS-polyacrylamide gels for biochemical studies. BioTechniques 28:232-238.
- Wang, H-C.R. and Fecteau, K.A. 2000. Detection of a novel quiescence-dependent protein kinase. Journal of Biological Chemistry 275: 25850-25857.
- Fecteau, KA., Mei, J., and Wang, H-C.R. 2002. Differential modulation of signaling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228. Journal of Pharmacology and Experimental Therapeutics, 300:890-899.
- Mei, J., Hu, H., McEntee, M., Plummer III, H., Song, P., and Wang, H-C.R. 2003 Transformation of noncancerous human breast epithelial cell MCF10A induced by the tobacco-specific carcinogen NNK. Breast Cancer Research and Treatment , 79:95-105.