Gen Wu
Address
421 E. Canfield Street, Suite 1106 Detroit, MI 48201Office Address
421 E. Canfield Street, Suite 1106
Detroit, MI 48201
Mentoring
Julio Pimentel (Graduated 6/14/2023)
Department
Oncology
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
Uddin, M.H., Pimentel, J.M., Chatterjee, M., Allen, J.E., Zhuang, Z., Wu, G.S., Targeting PP2A inhibits the growth of triple-negative breast cancer cells. Cell Cycle. 2020;19:592-600.
Kho, D.H., Uddin, M.H., Chatterjee, M., Vogt, A., Raz, A., and Wu, G.S. GP78 cooperates with dual-specificity phosphatase 1 to stimulate epidermal growth factor receptor-mediated extracellular signal-regulated signaling. Mol Cell Biol 2019;39:e00485-18.
Obrist, F., Michels, J., Durand, S., Chery, A., Pil, J., Levesque, S., Joseph, A., Astesana, V., Pietrocola, F., Wu, G.S., Castedo, M., Kroemer, G. Metabolic vulnerability of cisplatin-resistant cancers. EMBO J. 2018;13;37.
Yuan, X., Gajan, A., Chu Q., Xiong, H., Wu, K., Wu, G.S. Cancer Metastasis Rev. 2018 Mar 14. [Epub ahead of print]
Wang J, Kho DH, Zhou JY, Davis RJ, Wu GS. MKP-1 suppresses PARP-1 degradation to mediate cisplatin resistance. Oncogene. 2017;36:5939-47.
Yuan X, Kho D, Xu J, Gajan A, Wu K, Wu GS. ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells. Oncotarget. 2017;8:21626-38.
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, Kline CL, Prabhu VV, Wagner J, Ishizawa J, Madhukar N, Lev A, Baumeister M, Zhou L, Lulla A, Stogniew M, Schalop L, Benes C, Kaufman HL, Pottorf RS, Nallaganchu BR, Olson GL, Al-Mulla F, Duvic M, Wu GS, Dicker DT, Talekar MK, Lim B, Elemento O, Oster W, Bertino J, Flaherty K, Wang ML, Borthakur G, Andreeff M, Stein M, El-Deiry WS. Discovery and clinical introduction of first-in-class imipridone ONC201. Oncotarget. 2016;7:74380-92.
Xu HX, Wu KJ, Tian YJ, Liu Q, Han N, He XL, Yuan X, Wu GS, Wu KM. Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer: A systematic review and meta-analysis. Medicine. 2016;95:e4085.
Xu H, Wu K, Tian Y, Liu Q, Han N, Yuan X, Zhang L, Wu GS, Wu K. CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer. International journal of oncology. 2016; 49:1343-50.
Xu H, Tian Y, Yuan X, Liu Y, Wu H, Liu Q, Wu GS, Wu K. Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis. OncoTargets and therapy. 2016; 9:431-44.
Complete List of Publications:
Patents
Co-inventor: USPTO: US 20120276088-A1: Small Molecular (ONC201/TIC10) TRAIL gene induction by normal and tumor cells as an anticancer therapy. ONC201 has been granted Fast Track Designation and is being tested in phase I/II clinical trials.
Education/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
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