Gen Wu

Position Title

Professor
Basic Science

Office Location

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

Mailing Address

Karmanos Cancer Center
4100 John R
Mail Code: PR02DD
Detroit, MI 48201

Office Phone

(313) 578-4750

Education Training

(1992)  Ph.D. Peking Union Medical College, Beijing, China

Postgraduate Training
(1995-1999) Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA
(1993-1995) University of Pittsburgh School of Medicine, Pittsburgh, PA

Professional Experience

Faculty Appointments
(2015-Present)   Professor with Tenure, Department of Oncology and Department of Pathology, Wayne State University School of Medicine, Detroit, MI
(2004-Present)  Graduate Faculty Member, Cancer Biology Program, Wayne State University, Detroit, MI
(2011-2015)  Associate Professor with tenure, Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2005-2015)   Associate Professor with tenure, Karmanos Cancer Institute and Department of Pathology, Wayne State University School of Medicine, Detroit, MI
(1999-2005)   Assistant Professor, Karmanos Cancer Institute and Department of Pathology, Wayne State University School of Medicine, Detroit, MI

Hospital or Other Professional Appointments
(1999-Present)  Member, Karmanos Cancer Institute

Major Professional Societies

(2005-Present)  American Association for Cancer Research

Honors and Awards

(2007)  Karmanos Cancer Center Director's Award, Karmanos Cancer Institute (For the aticle by Wang et al in Cancer Research 66:8870-8877, 2006).

Courses taught

CB 7210: Fundamentals of Cancer Biology
CB 7220: Molecular Biology of Cancer Development
CB 7240: Cancer Chemotherapy
CB 7460: Mechanisms of Neoplasia - Alterations to Cellular Signaling

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.

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: more than 1,100 times).

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

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

8. 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).

9. 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.

10. Wang, J., and Wu. G.S. Role of autophagy in cisplatin resistance in ovarian cancer. J Biol Chem. 289:17163-73, 2014.

Faculty Status

Basic Science

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