School of Medicine

Wayne State University School of Medicine

Profile

Gen Sheng Wu, Ph.D.
Professor

2118 Prentis Building
110 E. Warren Avenue
Detroit, MI 48201

313-578-4750
Research Interests

My research interests are to understand the mechanisms of deregulated cell death pathways in human cancer and then target related pathways for the improvement of cancer therapies. Specifically, we focus on three areas. (1) We study the mechanisms of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. TRAIL is a member of the TNF family that selectively induces apoptosis of cancer and transformed cells, but not normal cells. However, many cancer cells are resistant to TRAIL and the underlying mechanisms are not fully understood. We are currently studying how cancer cells acquire resistance to TRAIL. (2) We study the regulation of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in cancer cells. MKP-1 is a member of the dual-specificity protein phosphatase family and an endogenous negative regulator of MAPK signaling. MKP-1 can dephosphorylate and inactivate all three major MAPKs, including JNK, p38 and ERK. MKP-1 is overexpressed in many cancer types and may regulate cancer cell drug resistance. It is established that the activation of MAPKs plays a critical role in the response of cancer cells to therapies. We are studying how MKP-1 inactivates MAPKs to impact cancer cell death. (3) We study the contribution of autophagy to drug resistance. Ultimately, this information will help design therapeutic strategies for the improvement of cancer treatment.

Education

1992 - Ph.D.
Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, China

Publications

1. Wu, G.S., Burns, T.F., McDonald III, E.R., Jiang, W., Meng, R., Krantz, I.D., Kao, G., Zhou, J.Y. Muschel, R., Hamilton, S.R., Spinner, N.B., Markowitz, S., Wu, G., El-Deiry, W.S. KILLER/DR5 is a DNA damage inducible p53 regulated death receptor gene. Nat. Genet. 17:141-143, 1997 (Highlighted in News & Views of the issue) (Google Scholar Citations: 1,000 times).

2. Wu, G.S. and Ding, Z. Caspase 9 is required for p53-dependent apoptosis and chemosensitivity in a human ovarian cancer cell line. Oncogene, 21:1-8, 2002.

3. Li, M., Zhou, J.Y., Ge, Y., Matherly, L. and Wu, G.S. The phosphatase MKP1 is a transcriptional target of p53 involved in cell cycle regulation. J Biol Chem, 278:41059-41068, 2003.

4. Zhou, J. Y., Liu, Y., and Wu, G.S. The role of mitogen-activated protein kinase phosphatase-1 in oxidative damage-induced cell death. Cancer Res. 66:4888-4894, 2006.

5. Wang, Z., Xu, J., Zhou, J.Y., Liu, Y. and Wu, G.S. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is required for cisplatin resistance. Cancer Res. 66:8870-8877, 2006.

6. Xu, J., Zhou, J.Y., Tainsky, MA and Wu, G.S. Evidence that TRAIL induction by 5-aza-2-deoxycytidine sensitizes the human breast cancer cell MDA213 to Adriamycin. Cancer Res. 67:1203-11, 2007.

7. Wang, J., Zhou, J.Y., and Wu, G.S. ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells. Cancer Res. 67:11933-41, 2007.

8. Wang, J., Zhou, J.Y, and Wu, G.S. Bim protein degradation contributes to cisplatin resistance. J Biol Chem. 286:22384-92, 2011.

9. Joshua E. Allen, J.E., Krigsfeld, G., Mayes, P.A., Patel, L., Dicker, D.T., Patel, A.S., Dolloff, N.G., Messaris, E., Scata, K.A., Wang, W., Zhou, J.Y., Wu, G.S., and El-Deiry, W.S. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction and potent anti-tumor effects. Science Translational Medicine. 5(171):171ra17, 2013. (Covered by Nature News).

10. Xu, J., Xu, Z., Zhou, J.Y., Zhuang, Z., Wang, E., Boerner, J and Wu, G.S. Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. J Biol Chem. 288:33263-71, 2013.