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. Deng, W, Kimura, Y, Gududuru, V, Wu, W, Balogh, A, Szabo, E, Thompson, KE, Yates, CR, Balazs, L, Johnson, LR, Miller, DD, Strobos, J, McCool, WS, Tigyi, GJ. Mitigation of the Hematopoietic and Gastrointestinal Acute Radiation Syndrome by Octadecenyl Thiophosphate, a Small Molecule Mimic of Lysophosphatidic Acid. Radiat Res, 2015.
  2. Umberger, R, Thompson, CL, Cashion, AK, Kuhl, D, Wan, J, Yates, CR, Muthiah, MP, Meduri, GU. Exaggerated plasma Interleukin 6, Interleukin 10, and Subsequent Development of Health Care-Associated Infections in Patients With Sepsis. Dimens Crit Care Nurs, 34 (2), 100-11, 2015.
  3. Patil, R, Szabó, E, Fells, JI, Balogh, A, Lim, KG, Fujiwara, Y, Norman, DD, Lee, SC, Balazs, L, Thomas, F, Patil, S, Emmons-Thompson, K, Boler, A, Strobos, J, McCool, SW, Yates, CR, Stabenow, J, Byrne, GI, Miller, DD, Tigyi, GJ. Combined Mitigation of the Gastrointestinal and Hematopoietic Acute Radiation Syndromes by an LPA2 Receptor-Specific Nonlipid Agonist. Chem Biol, 2015.
  4. Toutounchian, JJ, Steinle, JJ, Makena, PS, Waters, CM, Wilson, MW, Haik, BG, Miller, DD, Yates, CR. Modulation of Radiation Injury Response in Retinal Endothelial Cells by Quinic Acid Derivative KZ-41 Involves p38 MAPK. PLoS One, 9 (6), e100210, 2014.
  5. Zawaski, JA, Yates, CR, Miller, DD, Kaffes, CC, Sabek, OM, Afshar, SF, Young, DA, Yang, Y, Gaber, MW. Radiation Combined Injury Models to Study the Effects of Interventions and Wound Biomechanics. Radiat Res, 2014.
  6. Hosni-Ahmed, A, Sims, M, Jones, TS, Patil, R, Patil, S, Abdelsamed, H, Yates, CR, Miller, DD, Pfeffer, LM. EDL-360: A Potential Novel Antiglioma Agent. J Cancer Sci Ther, 6 (9), 370-377, 2014.
  7. 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.
  8. Patil, R, Hosni-Ahmed, A, Jones, TS, Patil, SA, Asres, LB, Wang, X, Yates, RC, Geisert, EE, Miller, DD. Synthesis and in vitro evaluation of novel 1,2,3,4-tetrahydroisoquinoline derivatives as potent antiglioma agents. Anticancer Agents Med Chem, 14 (3), 473-82, 2014.
  9. Thompson, KE, Zeng, K, Wilson, CM, Gaber, MW, Miller, DD, Yates, CR. Quinic acid derivative KZ-41 exhibits radiomitigating activity in preclinical models of radiation injury. Drug Dev Res, 75 (1), 29-36, 2014.
  10. 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.
  11. Winston, J, Chonchol, M, Gallant, J, Durr, J, Canada, RB, Liu, H, Martin, P, Patel, K, Hindman, J, Piontkowsky, D. Discontinuation of Tenofovir Disoproxil Fumarate for Presumed Renal Adverse Events in Treatment-Naïve HIV-1 Patients: Meta-analysis of Randomized Clinical Studies. HIV Clin Trials, 15 (6), 231-245, 2014.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. Patil R, Wang X-D, Orr WE, Yates CR, Geisert EE, and Miller DD. Synthesis and antiglioma activity of new tetrahydroisoquinolines. Medicinal Chemistry Research (20), 131-137, 2011.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. Song, P, Ma, F, Wang, F, Wang, X, Patil, R, Ramagiri, S, Orr, WE, Miller, DD, Geisert, E, Yates, CR. Plasma and cerebrospinal fluid pharmacokinetics of the novel tetrahydroisoquinoline EDL-155 in rats. Cancer Chemother Pharmacol, 61 (6), 1037-44, 2008.
  34. 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.
  35. Kosanam, H, Prakash, PK, Yates, CR, Miller, DD, Ramagiri, S. Rapid screening of doping agents in human urine by vacuum MALDI-linear ion trap mass spectrometry. Anal Chem, 79 (15), 6020-6, 2007.
  36. Gao, L, Flores, C, Fan-Ma, S, Miller, EJ, Moitra, J, Moreno, L, Wadgaonkar, R, Simon, B, Brower, R, Sevransky, J, Tuder, RM, Maloney, JP, Moss, M, Shanholtz, C, Yates, CR, Meduri, GU, Ye, SQ, Barnes, KC, Garcia, JG. Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations. Transl Res, 150 (1), 18-29, 2007.
  37. Gurley, BJ, Swain, A, Barone, GW, Williams, DK, Breen, P, Yates, CR, Stuart, LB, Hubbard, MA, Tong, Y, Cheboyina, S. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos, 35 (2), 240-5, 2007.
  38. Chen, ML, Straughn, AB, Sadrieh, N, Meyer, M, Faustino, PJ, Ciavarella, AB, Meibohm, B, Yates, CR, Hussain, AS. A modern view of excipient effects on bioequivalence: case study of sorbitol. Pharm Res, 24 (1), 73-80, 2007.
  39. Gourley, DR, Rowell, C, Wingate, L, Yates, CR, Gourley, GK, Miller, DD, Vleet, V. Status of PharmD/PhD programs in colleges of pharmacy: the University of Tennessee dual PharmD/PhD program. Am J Pharm Educ, 70 (2), 44, 2006.
  40. Gao, L, Grant, A, Halder, I, Brower, R, Sevransky, J, Maloney, JP, Moss, M, Shanholtz, C, Yates, CR, Meduri, GU, Shriver, MD, Ingersoll, R, Scott, AF, Beaty, TH, Moitra, J, Ma, SF, Ye, SQ, Barnes, KC, Garcia, JG. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol, 34 (4), 487-95, 2006.
  41. Song, P, Lamba, JK, Zhang, L, Schuetz, E, Shukla, N, Meibohm, B, Yates, CR. G2677T and C3435T genotype and haplotype are associated with hepatic ABCB1 (MDR1) expression. J Clin Pharmacol, 46 (3), 373-9, 2006.
  42. Gurley, BJ, Barone, GW, Williams, DK, Carrier, J, Breen, P, Yates, CR, Song, PF, Hubbard, MA, Tong, Y, Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos, 34 (1), 69-74, 2006.
  43. Parker, RB, Yates, CR, Laizure, SC, Weber, KT. P-glycoprotein modulates aldosterone plasma disposition and tissue uptake. J Cardiovasc Pharmacol, 47 (1), 55-9, 2006.
  44. Gupta, M, Yates, CR, Meibohm, B. SYBR Green-based real-time PCR allelic discrimination assay for beta2-adrenergic receptor polymorphisms. Anal Biochem, 344 (2), 292-4, 2005.
  45. Song, P, Meibohm, B, Yates, CR. LC/MS/MS in drug development: targeting the brain. Biotechniques, Suppl, 19-23, 2005.
  46. Dirks, NL, Huth, B, Yates, CR, Meibohm, B. Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther, 42 (12), 701-18, 2004.
  47. Meduri, GU, Yates, CR. Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS. Ann N Y Acad Sci, 1024, 24-53, 2004.
  48. Gupta, M, Song, P, Yates, CR, Meibohm, B. Real-time PCR-based genotyping assay for CXCR2 polymorphisms. Clin Chim Acta, 341 (1-2), 93-100, 2004.
  49. Yates, CR, Chang, C, Kearbey, JD, Yasuda, K, Schuetz, EG, Miller, DD, Dalton, JT, Swaan, PW. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res, 20 (11), 1794-803, 2003.
  50. Parker, RB, Yates, CR, Soberman, JE, Laizure, SC. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy, 23 (8), 979-87, 2003.
  51. Yates, CR, Zhang, W, Song, P, Li, S, Gaber, AO, Kotb, M, Honaker, MR, Alloway, RR, Meibohm, B. The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol, 43 (6), 555-64, 2003.
  52. Song, P, Li, S, Meibohm, B, Gaber, AO, Honaker, MR, Kotb, M, Yates, CR. Detection of MDR1 single nucleotide polymorphisms C3435T and G2677T using real-time polymerase chain reaction: MDR1 single nucleotide polymorphism genotyping assay. AAPS PharmSci, 4 (4), E29, 2003.
  53. Dalton, JT, Yates, CR, Yin, D, Straughn, A, Marcus, SL, Golub, AL, Meyer, MC. Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer. J Pharmacol Exp Ther, 301 (2), 507-12, 2002.
  54. Yates, CR, Vysokanov, A, Mukherjee, A, Ludden, TM, Tolley, E, Meduri, GU, Dalton, JT. Time-variant increase in methylprednisolone clearance in patients with acute respiratory distress syndrome: a population pharmacokinetic study. J Clin Pharmacol, 41 (4), 415-24, 2001.
  55. Yates, CR, Pui, CH, Evans, WE. Pharmacodynamic monitoring of cancer chemotherapy: childhood acute lymphoblastic leukemia as a model. Ther Drug Monit, 20 (5), 453-8, 1998.
  56. Loennechen, T, Yates, CR, Fessing, MY, Relling, MV, Krynetski, EY, Evans, WE. Isolation of a human thiopurine S-methyltransferase (TPMT) complementary DNA with a single nucleotide transition A719G (TPMT*3C) and its association with loss of TPMT protein and catalytic activity in humans. Clin Pharmacol Ther, 64 (1), 46-51, 1998.
  57. Krynetski, EY, Fessing, MY, Yates, CR, Sun, D, Schuetz, JD, Evans, WE. Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library. Pharm Res, 14 (12), 1672-8, 1997.
  58. Yates, CR, Krynetski, EY, Loennechen, T, Fessing, MY, Tai, HL, Pui, CH, Relling, MV, Evans, WE. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med, 126 (8), 608-14, 1997.
  59. Krynetski, EY, Tai, HL, Yates, CR, Fessing, MY, Loennechen, T, Schuetz, JD, Relling, MV, Evans, WE. Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms. Pharmacogenetics, 6 (4), 279-90, 1996.
  60. Tai, HL, Krynetski, EY, Yates, CR, Loennechen, T, Fessing, MY, Krynetskaia, NF, Evans, WE. Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. Am J Hum Genet, 58 (4), 694-702, 1996.
  61. Mukherjee, A, Kirkovsky, L, Yao, XT, Yates, RC, Miller, DD, Dalton, JT. Enantioselective binding of Casodex to the androgen receptor. Xenobiotica, 26 (2), 117-22, 1996.