Charles Ryan Yates, Pharm.D., Ph.D.

Professor
Pharmaceutical Sciences
Professor
Ophthalmology

Office: 446 Pharmacy Building
Tel: (901) 448-4135
cyates4@uthsc.edu

Education

  • Ph.D., UTHSC College of Graduate Health Sciences, Pharmaceutical Sciences
  • Pharm.D., UT, College of Pharmacy, Clinical Pharmacy
  • B.S., UT, Knoxville, Biological Sciences

Download My Curriculum Vitae

Research Description

Our laboratory has discovered two separate anti-inflammatory platforms. First,  we have identified and patented an orallly available quinic acid derivative, KZ-41, that exerts pro-survival activity under genotoxic stress. For example, KZ-41 improves survival in murine models of radiation and combined radiation and dermal injury models. Further, KZ-41 has been shown to protect human retinal endothelial cells from genotoxic stresses including radiation, melphalan, and high glucose.  Current research with quinic acid derivatives is focused on identifying the cellular receptor responsible for the pro-survival effects of KZ-41 and evaluating efficacy of topically applied KZ-41 in the murine oxygen-induced retinopathy model.  Second, we have identified an inhibitor of the cytoskeletal adaptor protein paxillin. We are currently using this platform as a tool to examine the effect of selective modulation of paxillin signaling using in vitro and in vivo models of aberrant proliferation and migration.

Research Interest/Specialty

Dr. Yates’ research interest is in drug discovery and development of small molecules that modulate pro-inflammatory signaling cascades associated with aberrant cellular proliferation and migration.

Research Keywords

Pharmacokinetics

Anti-inflammatory

Retinal Neovascularization

Proliferation

Migration

Publications

  1. Janice A. Zawaski, Charles R. Yates, Duane Miller, Caterina C. Kaffes, Omaima M. Sabek, Solmaz Afshar, Daniel A. Young, Yunzhi Yang, M. Waleed Gaber. Radiation combined injury models used to study the effect of interventions and wound biomechanics. (In preparation).
  2. Reba Umberger, Carol L. Thompson, Ann K. Cashion, David Kuhl, Jim Wan, Charles R. Yates, Muthiah P. Muthiah, Gianfranco U. Meduri. Exaggerated Systemic Inflammation and Subsequent Development of Health Care Associated Infections in Patients with Sepsis. American Journal of Critical Care (Under review).
  3. Jordan J. Toutounchian, Jena J. Steinle, Patrudu S. Makena, Christopher M. Waters, Matthew W. Wilson, Barrett G. Haik, Duane D. Miller, Charles R. Yates. Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. PLoS One (Under review).
  4. Zhang Q, Jiang Y, Toutounchian JJ, Pagadala J, Soderland D, Miller DD, Yates CR, and Steinle JJ. Protective effects of β1/β2-adrenergic receptor agonist, Compound 49b, in a mouse model of Oxygen-Induced Retinopathy. American Journal of Pathology (under review).
  5. Renukadevi Patil, Erzsébet Szabó, James I. Fells, Keng G. Lim, Yuko Fujiwara, Derek B. Norman, Andrea Balogh, Sue-Chin Lee, Louisa Balazs, Fridtjof Thomas, Shivaputra Patil, Karin Emmons-Thompson, Jur Strobos, Shannon W. McCool, C. Ryan Yates, Jennifer Stabenow, Gerrald B. Byrne, Duane D. Miller, Gábor J. Tigyi. Mitigation of High-dose Combined Acute Gastrointestinal and Hematopoietic Radiation Syndromes by a Sulfamoyl Benzoic Acid LPA2 Receptor-Specific Agonist. Chemistry and Biology (Under review).
  6. Slominski, AT, Kim, TK, Shehabi, HZ, Tang, EK, Benson, HA, Semak, I, Lin, Z, Yates, CR, Wang, J, Li, W, Tuckey, RC. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland. Mol Cell Endocrinol, 383 (1-2), 181-92, 2014.
  7. He, H, Williams-Guy, K, Pagadala, J, Presley, CS, Miller, DD, Steinle, JJ, Yates, CR. A sensitive and fast LC-MS/MS method for determination of β-receptor agonist JP-49b: Application to a pharmacokinetic study in rats. J Chromatogr B Analyt Technol Biomed Life Sci, 953-954C, 86-91, 2014.
  8. Renukadevi Patil, Amira Hosni-Ahmed, Terreia S. Jones, Shivaputra A. Patil, Likeselam B. Asres, Xiangdi Wang, Charles R. Yates, Eldon E. Geisert and Duane D. Miller. Synthesis and In Vitro Evaluation of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent Antiglioma Agents. Anti-Cancer Agents in Medicinal Chemistry, 14, 473-482, 2014.
  9. Karin Emmons Thompson, Kui Zeng, Christy M. Wilson, M. Waleed Gaber, Duane D. Miller, Charles R. Yates. Quinic acid derivative KZ-41 exhibits radiomitigating activity pre-clinical models of radiation injury. Drug Development Research (75), 29-36, 2014.
  10. Zhang, Q, Jiang, Y, Toutounchian, JJ, Soderland, C, Yates, CR, Steinle, JJ. Insulin-like growth factor binding protein-3 inhibits monocyte adhesion to retinal endothelial cells in high glucose conditions. Mol Vis, 19, 796-803, 2013.
  11. Wu, H, Pagadala, J, Yates, CR, Miller, D, Mahato, RI. Synthesis and characterization of an anti-apoptotic immunosuppressive compound for improving the outcome of islet transplantation. Bioconjug Chem, 24 (12), 2036-44, 2013.
  12. Zhang, Q, Jiang, Y, Toutounchian, J, Wilson, MW, Morales-Tirado, V, Miller, DD, Yates, CR, Steinle, JJ. Novel quinic acid derivative KZ-41 prevents retinal endothelial cell apoptosis without inhibiting retinoblastoma cell death through p38 signaling. Invest Ophthalmol Vis Sci, 54 (9), 5937-43, 2013.
  13. Gardner, LA, Desiderio, DM, Groover, CJ, Hartzes, A, Yates, CR, Zucker-Levin, AR, Bloom, L, Levin, MC. LC-MS/MS identification of the one-carbon cycle metabolites in human plasma. Electrophoresis, 34 (11), 1710-6, 2013.
  14. Kiss, GN, Lee, SC, Fells, JI, Liu, J, Valentine, WJ, Fujiwara, Y, Thompson, KE, Yates, CR, Sümegi, B, Tigyi, G. Mitigation of radiation injury by selective stimulation of the LPA(2) receptor. Biochim Biophys Acta, 1831 (1), 117-25, 2013.
  15. Zhang, Q, Guy, K, Pagadala, J, Jiang, Y, Walker, RJ, Liu, L, Soderland, C, Kern, TS, Ferry, R, He, H, Yates, CR, Miller, DD, Steinle, JJ. Compound 49b prevents diabetes-induced apoptosis through increased IGFBP-3 levels. Invest Ophthalmol Vis Sci, 53 (6), 3004-13, 2012.
  16. Schilling, BK, Hammond, KG, Bloomer, RJ, Presley, CS, Yates, CR. Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men. BMC Pharmacol Toxicol, 14, 52, 2012.
  17. Slominski, AT, Kim, TK, Chen, J, Nguyen, MN, Li, W, Yates, CR, Sweatman, T, Janjetovic, Z, Tuckey, RC. Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes. Int J Biochem Cell Biol, 44 (11), 2003-18, 2012.
  18. Slominski, AT, Kim, TK, Shehabi, HZ, Semak, I, Tang, EK, Nguyen, MN, Benson, HA, Korik, E, Janjetovic, Z, Chen, J, Yates, CR, Postlethwaite, A, Li, W, Tuckey, RC. In vivo evidence for a novel pathway of vitamin D₃ metabolism initiated by P450scc and modified by CYP27B1. FASEB J, 26 (9), 3901-15, 2012.
  19. Wang, XD, Freeman, NE, Patil, R, Patil, SA, Mitra, S, Orr, WE, Abner, CW, Yates, CR, Miller, DD, Geisert, EE. EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo. Anticancer Drugs, 23 (5), 494-504, 2012.
  20. Steinle, JJ, Zhang, Q, Thompson, KE, Toutounchian, J, Yates, CR, Soderland, C, Wang, F, Stewart, CF, Haik, BG, Williams, JS, Jackson, JS, Mandrell, TD, Johnson, D, Wilson, MW. Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis. Invest Ophthalmol Vis Sci, 53 (4), 2439-45, 2012.
  21. Zeng, K, Thompson, KE, Presley, CS, Miller, DD, Yates, CR. Preclinical pharmacokinetics of the radiomitigator KZ-41 in rats. Xenobiotica, 41 (11), 1006-12, 2011.
  22. Gupte, R, Patil, R, Liu, J, Wang, Y, Lee, SC, Fujiwara, Y, Fells, J, Bolen, AL, Emmons-Thompson, K, Yates, CR, Siddam, A, Panupinthu, N, Pham, TC, Baker, DL, Parrill, AL, Mills, GB, Tigyi, G, Miller, DD. Benzyl and naphthalene methylphosphonic acid inhibitors of autotaxin with anti-invasive and anti-metastatic activity. ChemMedChem, 6 (5), 922-35, 2011.
  23. Vaddady, PK, Mehrotra, N, Zhang, X, Yates, CR, Moore, BM, Meibohm, B. Pharmacokinetics of a combination of Δ9-tetrahydro-cannabinol and celecoxib in a porcine model of hemorrhagic shock. Biopharm Drug Dispos, 32 (2), 89-98, 2011.
  24. Kosanam, H, Ma, F, He, H, Ramagiri, S, Gududuru, V, Tigyi, GJ, Van Rompay, K, Miller, DD, Yates, CR. Development of an LC-MS/MS assay to determine plasma pharmacokinetics of the radioprotectant octadecenyl thiophosphate (OTP) in monkeys. J Chromatogr B Analyt Technol Biomed Life Sci, 878 (26), 2379-83, 2010.
  25. Nassr, M, Wang, X, Mitra, S, Freeman-Anderson, NE, Patil, R, Yates, CR, Miller, DD, Geisert, EE. Treating retinoblastoma in tissue culture and in a rat model with a novel isoquinoline derivative. Invest Ophthalmol Vis Sci, 51 (7), 3813-9, 2010.
  26. Zeng, K, Thompson, KE, Yates, CR, Miller, DD. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents. Bioorg Med Chem Lett, 19 (18), 5458-60, 2009.
  27. Li, S, Stuart, L, Zhang, Y, Meduri, GU, Umberger, R, Yates, CR. Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype. J Clin Pharm Ther, 34 (4), 447-55, 2009.
  28. Ramagiri, S, Ma, F, Kosanam, H, Wang, X, Patil, R, Miller, DD, Geisert, E, Yates, CR. Fast and sensitive liquid chromatography/electrospray mass spectrometry method to study ocular penetration of EDL-155, a novel antitumor agent for retinoblastoma in rats. J Mass Spectrom, 44 (5), 786-93, 2009.
  29. Dirks, NL, Li, S, Huth, B, Hochhaus, G, Yates, CR, Meibohm, B. Transrepression and transactivation potencies of inhaled glucocorticoids. Pharmazie, 63 (12), 893-8, 2008.
  30. Ramagiri, S, Gupte, R, Rakov, I, Yates, CR, Miller, DD. Quantitative chiral analysis of phthaloylglutamic acid and related analogs by a single ratio kinetic method using electrospray ionization and matrix-assisted laser desorption techniques. Rapid Commun Mass Spectrom, 22 (5), 639-46, 2008.