School of Medicine

Wayne State University School of Medicine

Gen Sheng Wu

Gen Sheng Wu, Ph.D.
Professor
421 E. Canfield Street, Suite 1106
Detroit, MI 48201
313-578-4750
wug@karmanos.org


Research Interests:

  • MAPKs and their phosphatases in cancer cells
  • TRAIL signaling and resistant mechanisms
  • Chemosensitivity and drug resistance

Research Description:
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 two 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) Another interest is 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.

Selected Publications:

Wang J, Zhou, JY, Kho, D, Reiners, JJ Jr, Wu, GS. Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy. Autophagy. 2016;12:1791-1803.

 

Allen, JE, Krigsfeld, G, Patel, L, Mayes, PA, Dicker, DT, Wu, GS, El-Deiry, WS. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL-pathway. Mol Cancer 2015;14:99.

 

Xu, J, Zhou, JY, Xu, Z, Kho, DH, Zhuang, Z, Raz, A, Wu, GS. The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling. Cell Cycle. 2014;13:3750-8.

Michels J, Obrist F, Vitale I, Lissa D, Garcia P, Behnam-Motlagh P, Kohno K, Wu GS, Brenner C, Castedo M, Kroemer G. MCL-1 dependency of cisplatin-resistant cancer cells. Biochem Pharmacol. 2014 Aug 12.

Wang J, Wu GS. Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem. 2014;289:17163-73.

Haagenson KK, Zhang JW, Xu Z, Shekhar MP, Wu GS. Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity. Oncotarget. 2014;5:1101-10.

Xu J, Xu Z, Zhou JY, Zhuang Z, Wang E, Boerner J, Wu GS. Regulation of the Src-PP2A Interaction in Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis. J Biol Chem. 2013;288:33263-71.

Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O, Senovilla L, Talhaoui I, Guegan J, Enot DP, Talbot M, Robin A, Girard P, Oréar C, Lissa D, Sukkurwala AQ, Garcia P, Behnam-Motlagh P, Kohno K, Wu GS, Brenner C, Dessen P, Saparbaev M, Soria JC, Castedo M, Kroemer G. Cisplatin resistance associated with PARP hyperactivation. Cancer Res. 2013;73:2271-80.

Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W, Zhou JY, Wu GS, El-Deiry WS. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013;5:171ra17.

Education and Training:
PhD (1992): Peking Union Medical College, Beijing, China
Post-Doc (1993-1995): University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Post-Doc (1995-1999): Howard Hughes Medical Institute at University of Pennsylvania, Philadelphia, Pennsylvania

Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7220 Molecular Biology of Cancer Development
CB7240 Principle of Cancer Therapy
CB7300 Special Topics F31 Grant Writing Course
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling
CB7700 Recent Developments in Cancer Biology