chen.844@osu.edu

Ching-Shih Chen
PhD
Professor
Medicinal Chemistry and Pharmacognosy
Internal Medicine and Urology
336 Parks Hall
Phone: 
614-688-4008

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.

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
  • PhD, 1985, University of Wisconsin

Recent Publications

  • Y.-C. Tseng, S. K. Kulp, I-L. Lai, E.-C. Hsu, W. A. He, D. E. Frankhouser, P. S. Yan, M. Bloomston, G. B. Lesinski, G. Marcucci, D. C. Guttridge, T. Bekaii-Saab, and C.-S. Chen (2015) “Preclinical investigation of the novel histone deacetylase inhibitor AR-42 in the treatment of cancer-induced cachexiaJ. Natl. Cancer Inst., Accepted pending minor revision
  • C.-C. Chou, H.-C. Chuang, S. B. Salunke, S. K. Kulp, and C.-S. Chen (2015) “A novel HIF-1α-integrin-linked kinase regulatory loop that facilitates hypoxia-induced HIF-1 expression and epithelial-mesenchymal transition in cancer cellsOncotarget, 6, 8271-85
  • R. Yan,  H.-C. Chuang,  N. Kapuriya, C.-C. Chou, P.-T. Lai, H.-W. Chang, C.-N. Yang, S. K. Kulp, and C.-S. Chen (2015) “Exploitation of the Ability of -Tocopherol to Facilitate Membrane Co-localization of Akt and PHLPP1 to Develop PHLPP1-Targeted Akt InhibitorsJ. Med. Chem., 58, 2290-8
  • E.-C. Hsu, S. K. Kulp, H.-L. Huang, H.-J. Tu, M.-W. Chao, Y.-C. Tseng, M.-C. Yang, S. B. Salunke, N. J. Sullivan, W.-C. Chen, J. Zhang, C.-M. Teng, W.-M. Fu, D. Sun, M. S. Wicha, C. L. Shapiro, and C.-S. Chen (2015) “Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer” Oncogene, under revision
  • S. B. Salunke, A. K. Azad, N. P. Kapuriya, J.-M. Balada-Llasat, P. Pancholi, L. S. Schlesinger, and C.-S. Chen (2015) “Design and Synthesis of Novel Anti-tuberculosis Agents from the Celecoxib Pharmacophore” Bioorg. Med. Chem, 23, 1935-1943
  • P.-C. Chu, M.-C. Yang, S. K. Kulp, S. B. Salunke, Y.-S. Shan, C.-T. Lee, M.-D. Lai, L. A. Shirley, T. Bekaii-Saab, and C.-S. Chen (2015) “Regulation of Oncogenic KRAS Signaling via a Novel KRAS-ILK-hnRNPA1 Regulatory Loop in Pancreatic Cancer Cells” under review
  • E.-C. Hsu, S. K. Kulp, H.-L. Huang, H.-J. Tu, S. B. Salunke, N. J. Sullivan, D. Sun, M. S. Wicha, C. L. Shapiro, and C.-S. Chen (2015) “ILK is Responsible for -Secretase Integrity in Caveolae to Regulate Notch1 Activation in Breast Cancer Cells” Neoplasia, under revision
  • E. M. E. Dokla, C.-S. Fang, P.-T. Lai, S. K. Kulp, N. S. M. Ismail, R. A.T. Serya, K. A. M. Abouzid, and Ching-Shih Chen (2015) “Development of Potent Adenosine Monophosphate-Activated Protein Kinase Activators” under review
  • R, Mani, Y. Mao, F. W. Frissora, C.-L. Chiang, J. Wang, Y. Zhao, Y. Wu, B. Yu, R. Yan, X. Mo, L. Yu, J. Flynn, J. Jones, L. Andritsos, S. Baskar, C. Rader, M. A. Phelps, C.-S. Chen, R. J. Lee, J. C. Byrd, L. J. Lee, N. Muthusamy (2015) “Tumor antigen ROR1 targeted drug delivery mediated selective leukemic but not normal B-cell cytotoxicity in chronic lymphocytic leukemia” Leukemia 29, 346-355
    R. L. Plews, A. M. Yusof, C. Wang, M. Saji, X. Zhang, C.-S. Chen, M. D. Ringel, J. E. Phay “A Novel Dual AMPK Activator/mTOR Inhibitor Inhibits Thyroid Cancer Cell Growth” J. Clin. Endocrinol. Metab., accepted for publication 2015 Feb 24:jc20141777. [Epub ahead of print]
  • T.-M. Liu, Y. Ling, J.A. Woyach, K. Beckwith, Y.Y. Yeh, E. Hertlein, Z. Zhang, A. Lehman, F. Awan, J.A. Jones, L.A. Andritsos, K. Maddocks, J. MacMurray, S.B. Salunke, C.-S. Chen, M.A. Phelps, J.C. Byrd, A.J. Johnson (2015) “OSU-T315: a novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells” Blood 125, 284-295

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