Dr Zhou
Jia Zhou, Ph.D. Professor, Department Pharmacology and Toxicology

Contact Information:
Phone: (409) 772-9748
Fax: (409) 772-9648
Email: jizhou@utmb.edu

B.Sc., 1991, Central China Normal University, Wuhan, China (Chemistry)
M.Sc., 1994, Nankai University, Tianjin, China (Organic Chemistry)
Ph.D., 1997, Nankai University, Tianjin, China (Organic Chemistry)
Postdoctoral Fellow, 1999-2001, Department of Chemistry, University of Virginia
Postdoctoral Fellow, 2001-2003, Drug Discovery Program, Georgetown University Medical Center
Residential School on Medicinal Chemistry, 2009, Drew University, Madison, NJ

Research Interests:
My research interests are broadly based on the interface of synthetic organic chemistry and medicinal chemistry, and in particular on the drug discovery of bioactive molecules to probe biological systems or act as potential therapeutic agents in neuroscience, cancer/inflammation, infectious diseases, and other human conditions. With this general idea in mind, and in active collaboration with other biologists and pharmacologists, my group is dedicated to establish a strong and creative research program that applies state-of-the-art chemical approaches to biological problems impacting diagnosis, prevention and treatment of human diseases.

One of our current efforts is focused on design and synthesis of small molecules for probing function and development of pharmacological tools for understanding the workings of the brain and that of novel therapies for central nervous system (CNS) disorders such as drug abuse and addiction, depression, schizophrenia, pain, and neurodegenerative diseases. The proposed projects in this area include the identification, characterization and optimization of allosteric modulators and bitopic ligands of 5-HT2C receptor, neuromedin U receptor 2 (NMUR2) ligands, and other GPCR ligands. We are also working on the discovery of DeltaFosB modulators, neurexin modulators, and FGF14/Nav1.6 channel complex protein-protein interaction modulators as CNS probes and potential therapeutics

Another line of research development centers on the establishment of novel chemical libraries aiming at mechanism-based or lead compound-based drug discovery for cancer/inflammation, particularly by targeting Bcl-2 family proteins and apoptosis pathways, transcription factors as well as epigenetic therapy with the aid of molecular docking and chemical synthesis. Specifically, we are developing Bax activators, BH4 domain antagonists of Bcl2, orally bioavailable STAT3 inhibitors, AP-1 inhibitors, KLF5 inhibitors, KRAS plasma membrane localization inhibitors, cystathionine-β-synthase (CBS) inhibitors, NNMT inhibitors, and BRD4 inhibitors as a new class of preventive/therapeutic agents for various human cancers including brain tumors, breast cancer, lung cancer, head/neck cancer, colorectal cancer, prostate cancer, and pancreatic cancer as well as inflammation.

Our research efforts on developing chemical probes include design and synthesis of small molecules targeting EPAC, which are exchange proteins directly activated by cAMP including cAMP-regulated guanine nucleotide exchange factors. These EPAC inhibitors have also demonstrated as promising therapeutics for a variety of indications including infectious diseases. Last but not least, we are also working on natural product-inspired diversity-oriented synthesis that may lead to exciting potentials for discovery of novel targets and drug candidates.

Selected Publications:

  1. J. S. Rudra, Y. Ding, H. Neelakantan, C. Ding, R. Appavu, S. J. Stutz, J. D. Snook, H.Y. Chen, K. A. Cunningham, J. Zhou. Suppression of Cocaine-evoked Hyperactivity by Self-adjuvanting and Multivalent Peptide Nanofiber Vaccines. ACS Chem. Neurosci., 2016, DOI: 10.1021/acschemneuro.5b00345.
  2. N. Ye, Y. Zhu, H.J. Chen, Z. Liu, F. C. Mei, C. Wild, H.Y. Chen, X. Cheng, and J. Zhou. Structure-Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-Oxo-N'-Phenyl-Acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists. J. Med. Chem., 2015, 58 (15), 6033-6047.
  3. B. Han, D. Park, R. Li, M. Xie, T. Owonikoko, G. Sica, C. Ding, J. Zhou, A. Magis, S. Ramalingam, F. Khuri, W. Curran, X. Deng. Bcl2 BH4 Antagonist for Lung Cancer Therapeutics. Cancer Cell, 2015, 27 (6), 852-863. 
  4. C. Ding, L. Wang, H. Chen, C. Wild, N. Ye, Y. Ding, T. Wang, M. A. White, Q. Shen, J. Zhou. ent-Kaurane-Based Regio- and Stereoselective Inverse Electron Demand Hetero-Diels-Alder Reactions: Synthesis of Dihydropyran-Fused Diterpenoids. Org. Biomol. Chem. 2014, 12 (42), 8442-8452.
  5. M. Xin, R. Li, D. Park, M. Xie, T. K. Owonikoko, G. L. Sica, P. E. Corsino, J. Zhou, C. Ding, M. A. White, A. T. Magis, S. S. Ramalingam, W. J. Curran, F. R. Khuri, X. Deng, Small Molecule Bax Agonists for Cancer Therapy. Nature Communications, 2014, 5, 4935. DOI: 10.1038/ncomms5935.
  6. C. Ding, Y. Zhang, H. Chen, Z. Yang, C. Wild, C. D. Ester, A. Xiong, M. A. White, Q. Shen, J. Zhou. Oridonin Ring A-Based Diverse Constructions of Enone Functionality: Identification of Dienone Analogues Effective for Highly Aggressive Breast Cancer by Inducing Apoptosis. J. Med. Chem. 2013, 56 (21), 8814-8825. 
  7. H. Chen, T. Tsalkova, O. G. Chepurny, F. C. Mei, G. G. Holz, X. Cheng, J. Zhou, Identification and Characterization of Small Molecules as Potent and Specific Epac2 Antagonists, J. Med. Chem., 2013, 56 (3), 952-962. 
  8. C. Ding, Y. Zhang, H. Chen, C. Wild, T. Wang, M. White, Q. Shen, J. Zhou. Overcoming Synthetic Challenges of Oridonin A-Ring Structural Diversification: Regio- and Stereoselective Installation of Azides and 1,2,3-Triazoles at the C-1, C-2, or C-3 Position. Org. Lett., 2013, 15 (14), 3718-3721.   
  9.  C. Ding, Y. Zhang, H. Chen, L. Chu, Z. Yang, C. Wild, H. Liu, Q. Shen, J.  Zhou. Novel Nitrogen-Enriched Oridonin Analogs with Thiazole-Fused A-Ring: Protecting Group-Free Synthesis, Enhanced Anticancer Profile, and Improved Aqueous Solubility. J. Med. Chem. 2013, 56 (12), 5048-5058.  
  10.  C. Ding, N. M. Bremer, T. D. Smith, P. K. Seitz, N. C. Anastasio, K. A. Cunningham, J. Zhou. Exploration of Synthetic Approaches and Pharmacological Evaluation of PNU-69176E and Its Stereoisomer as 5-HT2C Receptor Allosteric Modulators. ACS Chem. Neurosci., 2012, 3 (7), 538-545. 

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