Gen Sheng Wu (ah2761)
University information
Contact information
Cancer Biology Program
Professor
421 E. Canfield Street, Suite 1106
Detroit, MI 48201
Julio Pimentel (Graduated 6/14/2023)
Oncology
- MAPKs and their phosphatases in cancer cells
- TRAIL signaling and resistant mechanisms
- Chemosensitivity and drug resistance
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.
Pimentel, J.M., Zhou, J.Y., Kim, S., Gurdziel, K., Wu, G.S. The role of the immune response and inflammatory pathways in TNF-related apoptosis-inducing ligand (TRAIL) resistance in triple-negative breast cancer cells. Am J. Cancer Res. 2023 Oct 15;13(10):4678-4692.
Pimentel, J.M., Zhou, J.Y., Wu, G.S. The role of TRAIL in apoptosis and immunosurveillance in cancer. Cancers 2023, 15(10), 2752.
Pimentel, J.M., Zhou, J.Y., Wu, G.S. Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells. Mol Carcinog. 2023 Feb;62(2):135-144.
Uddin MH, Zhou JY, Pimentel J, Patrick SM, Kim S, Shekhar MP, Wu GS. Proteomic Analysis Identifies p62/SQSTM1 as a Critical Player in PARP Inhibitor Resistance. Front Oncol. 2022 Jun 29;12:908603. doi: 10.3389/fonc.2022.908603. eCollection 2022.
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., 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., X, J., Gajan, A., Wu, K., Wu, G.S. ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells. Oncotarget. 8(13): 21626-38, 2017.
Complete List of Publications:
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 II/III clinical trials.
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
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
Department of Pathology
1245 Elliman Building
421 East Canfield St
Detroit, MI 48201
1992 - Ph.D.
Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, China
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.
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.
Oncology
Professor
Basic Science
Karmanos Cancer Institute
Elliman Building - 1246
421 E. Canfield
Detroit, MI 48201
Karmanos Cancer Center
4100 John R
Mail Code: EL01DD
Detroit, MI 48201
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
(1992) Ph.D. Peking Union Medical College, Beijing, China
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
(2005-Present) American Association for Cancer Research
(2007) Karmanos Cancer Center Director's Award, Karmanos Cancer Institute (For the aticle by Wang et al in Cancer Research 66:8870-8877, 2006).
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
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.
1. 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.
2. Wang, J., Zhou, J.Y, and Wu, G.S. Bim protein degradation contributes to cisplatin resistance. J Biol Chem. 286:22384-92, 2011.
3. 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.
4. 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.
5. Wang, J., and Wu. G.S. Role of autophagy in cisplatin resistance in ovarian cancer. J Biol Chem. 289:17163-73, 2014.
6. Wang, J., Kho, D.H., Zhou, J.Y. Wu, G.S. MKP-1 suppresses PARP-1 degradation to mediate cisplatin resistance. Oncogene. 36(43):5939-47, 2017.
7. Wang. J., Zhou, J.Y., Kho, D., Reiners, J.J. Jr., Wu, G.S. Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy. Autophagy. Oct2;12(10):1791-1803, 2016.
8. 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 growh factor receptor-mediated extracellular signal-regulated signaling. Mol Cell Biol 39: pii: e00485-18, 2019.
9. Pimentel, J.M., Zhou, J.Y., Kim, S., Gurdziel, K., and Wu, G.S. The role of the immune response and inflammatory pathways in TNF-related apoptosis-inducing ligand (TRAIL) resistance in triple-negative breast cancer cells. Am J. Cancer Res. 2023 Oct 15;13(10):4678-4692.
10. Pimentel, J.M., Zhou, J.Y., and Wu, G.S. Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells. Mol Carcinog. 2023 Feb;62(2):135-144.
