Professional Interests
Structure- and mechanism-based design of novel therapeutic agents that selectively target metabolic and survival machineries in cancer cells at cellular or epigenetic levels.
Dr. Chen's research focuses on exploring signaling pathways that govern cancer cell survival as targets for drug discovery and design. He employs a multidisciplinary approach to identify new molecular targets by combining a wide range of expertise encompassing synthetic medicinal chemistry, molecular and cell biology, molecular pharmacology, and animal models in his research team. His laboratory has developed a series of novel small-molecule agents that target different molecular defects related to kinase signaling, epigenetics, and cell metabolism in cancer cells, including phosphoinositide-dependent kinase (PDK)-1/Akt inhibitors, histone deacetylase (HDAC) inhibitors, Bcl-2/Bcl-xL inhibitors, protein kinase C delta activators, AMPK activators, and glucose transporter inhibitors. These novel agents mediate antiproliferative effects through mechanisms distinct from that of conventional chemotherapeutic regimens, which will provide a rational approach for molecular targeted cancer therapy. Currently, many of these promising compounds are undergoing preclinical development in his laboratory using a number of cancer models including those of prostate, breast, liver, and pancreas. Two of these agents, the PDK-1/Akt inhibitor OSU-03012 (AR12) and the HDAC inhibitor HDAC-42 (AR42), are currently undergoing Phase I clinical trials at OSU James Cancer Hospital and other cancer hospitals.
These studies are supported by research grants by the National Cancer Institute, Department of Defense Prostate Cancer Research Program, Leukemia and Lymphoma Society, and Stephanie Spileman Fund for Breast Cancer Research.
Recent Publications
- P.-H. Huang, H.-C. Chuang, S.-L. Lee, H.-C. Yang, C.-C. Chiou, H.-C. Chiu, D. Wang, S. K. Kulp, and C.-S. Chen (2013) “Vitamin E Facilitates Akt dephosphorylation through membrane recruitment of PHLPP” Science Signaling 6 (267), ra19
- L. D. Berman-Booty, P.-C. Chu, J. M. Thomas-Ahner, D. Wang, T. Yang, S. K. Clinton, S. K. Kulp, C.-S. Chen (2013) “Suppression of Prostate Epithelial Proliferation and Intraprostatic Pro-Growth and Survival Signaling in Transgenic Mice by a Novel Energy Restriction-Mimetic Agent” Cancer Prev. Res. 6, 232-241
- D. Wang, P.-C. Chu, C.N. Yang, R. Yan, Y.-C. Chung, S. K. Kulp, and C.-S. Chen (2012) “Development of a Novel Class of Glucose Transporter Inhibitors” J. Med. Chem. 55, 3827-3836
- P.-C. Chu, H.-C. Chuang, S. K. Kulp, and C.-S. Chen (2012) “The mRNA-Stabilizing Factor HuR Is Targeted by b-TrCP for Degradation in response to Glycolysis Inhibition” J. Biol. Chem. 287, 43639-50
- S. Wei, P.-C. Chu, H.-C. Chuang, W.-C. Hung, S. K. Kulp, and C.-S. Chen (2012) “Targeting the oncogenic E3 ligase Skp2 in prostate and breast cancer cells with a novel energy restriction-mimetic agent” PLoS One, 7, e47298
- H.-C. Chuang, N. Kapuriya, S. K. Kulp, C.-S. Chen, and C. L. Shapiro (2012) “Differential anti-proliferative activities of poly(ADP-ribose)polymerase (PARP) inhibitors in triple-negative breast cancer cells” Breast Cancer Res. Treat. 134, 649-659
- H.-Y. Lin, Y.-C. Kuo, Y.-I. Weng, T. H.-M. Huang, S.-P. Lin, D.-M. Niu, and C.-S. Chen (2012) “Activation of silenced tumor suppressor genes in prostate cancer cells by a novel glucose transporter inhibitor” Prostate 72, 1767-78
- H.-C. Chiu, D. Wang, S.-L. Lee, S. K. Kulp, S.-L. Yu, L.-J. Teng, and C.-S. Chen (2012) “Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus” Bioorg. Med. Chem. 20, 4653-4660
- M.-C. Chen, C.-H. Chen, H.-C. Chuang, S. K. Kulp, C.-M. Teng, and C.-S. Chen (2011) “Novel mechanism by which histone deacetylase inhibitors facilitate topoisomerase IIa degradation in hepatocellular carcinoma cells” Hepatology, 53, 148-159
- H. A. Omar, Y. C.-C. Chou, L. Berman-Booty, Y. Ma, J.-H. Hung, S. K. Kulp. T. Kogure, T. Patel, D. Wang, N. Muthsuamy, J. C. Byrd, and C.-S. Chen (2011) “Antitumor effects of OSU-2S, a non-immunosuppressive analogue of FTY720, in hepatocellular carcinoma” Hepatology, 53, 1943-1958
- C.H. Chen, P.-H. Huang, P.-C. Chu, M.-C. Chen, C.-C. Chou, D.-S. Wang, S. K. Kulp, C.-M. Teng, and C.-S. Chen (2011) “Epigenetic activation of KLF6 tumor suppressor gene expression by energy restriction in prostate cancer cells, in part, through histone modifications” J. Biol. Chem. 286, 9968-9976
- P.-H. Huang, C.-H. Chen, C.-C. Chiu, A. M. Sargeant, S. K. Kulp. C.-M. Teng, J. C. Byrd, and C.-S. Chen (2011) “Histone deacetylase inhibitors stimulate histone H3 lysine 4 methylation, in part, via transcriptional repression of histone H3 lysine 4 demethylases” Mol. Pharmacol., 79. 197-206
- S.-L. Lee, E.-C. Hsu, C.-C. Chiu, H.-C. Chuang, L.-Y. Bai, S. K. Kulp, and C.-S. Chen (2011) “Identification and characterization of a novel integrin-linked kinase inhibitor” J. Med. Chem., 54, 6364-74
- K.-H. Lee, E.-C. Hsu, J.-H. Guh, D. Wang, S.K. Kulp, C. L. Shapiro, and C.-S. Chen (2011) “Targeting energy metabolism and oncogenic signaling pathways in triple-negative breast cancer by a novel AMPK activator” J. Biol. Chem., 286, 39247-39258
Honors
- 2010 Distinguished Scholar Award, The Ohio State University
- 2005 Lucius A. Wing Chair of Cancer Research and Therapy
- 2004 AAAS Fellow
- 2004 Recipient, AACR Grants in Translational Cancer Research
- 2004 Fellow
- 2003 Kimberly Chair Professorship, The Ohio State University College of Pharmacy
- NIH IRG Basic Mechanisms for Cancer Therapeutics Board
- Advisory Board for Institute for Biological Chemistry Academia Sinica (Taiwan)
- DoD Prostate Cancer Program Review Panel (CET-3)
Education
- Postdoctoral, 1986, University of Wisconsin
- Ph.D., 1985, University of Wisconsin
