Michael H. Court,
Professor and William R. Jones Endowed Chair
Department of Veterinary Clinical Sciences
Diplomate, American College of Veterinary Anesthesiologists
Queensland University, BVSc Hons., 1981
University of Sydney, Internship, Small Animal, 1982
Tufts University, Residency, Anesthesia, 1985
Flinders University, Fellowship, Pharmacology, 1999
Tufts University, PhD, Pharmacology and Experimental Therapeutics 2000
Active Call for DNA Samples
We are currently seeking DNA samples from sighthounds who may have experienced either delayed postoperative bleeding or an adverse reaction to an anesthesia or sedative drug that caused unexpected slow recovery or increased body temperature (malignant hyperthermia). More information including contact email is provided in the following flier:WSU Sighthound Genetics Study Advertisement - 11-2-2018
My laboratory primarily conducts pharmacogenomic research, including studies designed to identify genetic variants and related mechanisms that determine interindividual differences in drug effect (both beneficial and adverse). The long-term goal of our work is to translate these findings into clinical practice and improve the treatment of important diseases through pharmacogenomic-guided selection of the most effective and safest drug and drug dose for the individual patient (individualized therapeutics). One of the main projects in our laboratory is attempting to understand the molecular and genetic basis for increased sensitivity of some sighthound dog breeds (such as greyhounds) to certain injectable anesthetic agents. We are also trying to find the genetic cause of several other sighthound problems, including hyperfibrinolysis causing delayed postoperative bleeding and stress/anesthesia induced hyperthermia. The ultimate goal of this work is to develop predictive genetic and phenotypic tests to identify dogs at risk.
Perez Jimenez TE, Kukanich B, Joo H, Mealey KL, Grubb TL, Greene SA, Court MH. Oral Coadministration of Fluconazole with Tramadol Markedly Increases Plasma and Urine Concentrations of Tramadol and the O-Desmethyltramadol Metabolite in Healthy Dogs. Drug Metab Dispos. 2019 Jan;47(1):15-25. doi: 10.1124/dmd.118.083444. Epub 2018 Oct 26. PMID: 30366901.
Lee PM, Faus MCL, Court MH. High interindividual variability in plasma clopidogrel active metabolite concentrations in healthy cats is associated with sex and cytochrome P450 2C genetic polymorphism. J Vet Pharmacol Ther. 2019 Jan;42(1):16-25. doi: 10.1111/jvp.12717. Epub 2018 Sep 24. PMID: 30251376.
Kwara A, Yang H, Antwi S, Enimil A, Gillani FS, Dompreh A, Ortsin A, Opoku T, Bosomtwe D, Sarfo A, Wiesner L, Norman J, Alghamdi WA, Langaee T, Peloquin CA, Court MH, Greenblatt DJ. Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old. Antimicrob Agents Chemother. 2018 Dec 21;63(1). pii: e01657-18. doi: 10.1128/AAC.01657-18. Print 2019 Jan. PMID: 30397066.
Perez Jimenez TE, Mealey KL, Schnider D, Grubb TL, Greene SA, Court MH. Identification of canine cytochrome P-450s (CYPs) metabolizing the tramadol (+)-M1 and (+)-M2 metabolites to the tramadol (+)-M5 metabolite in dog liver microsomes. J Vet Pharmacol Ther. 2018 Dec;41(6):815-824. doi: 10.1111/jvp.12706. Epub 2018 Aug 16. PMID: 30113702.
Malkawi M, Woolcock AD, Lee PM, Court MH, Moore GE, Hogan DF. Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study. J Feline Med Surg. 2018 Nov 14:1098612X18810887. doi: 10.1177/1098612X18810887. [Epub ahead of print] PMID: 30427274.
Haines JM, Lee PM, Hegedus RM, Hwang JK, Court MH. Investigation into the causes of aspirin resistance in healthy dogs. J Vet Pharmacol Ther. 2018 Oct 9. doi: 10.1111/jvp.12725. [Epub ahead of print] PMID: 30302763.
Martinez MN, Court MH, Fink-Gremmels J, Mealey KL. Population variability in animal health: Influence on dose-exposure-response relationships: Part I: Drug metabolism and transporter systems. J Vet Pharmacol Ther. 2018 Aug;41(4):E57-E67. doi: 10.1111/jvp.12670. Epub 2018 Jun 19. Review. PMID: 29917248.
Morassi A, Rivera-Vélez SM, Slovak JE, Court MH, Villarino NF. Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co-incubated dexamethasone and prednisolone. J Vet Pharmacol Ther. 2018 Aug;41(4):513-521. doi: 10.1111/jvp.12507. Epub 2018 Apr 23. PMID: 29687456.
Dompreh A, Tang X, Zhou J, Yang H, Topletz A, Adu Ahwireng E, Antwi S, Enimil A, Langaee T, Peloquin CA, Court MH, Kwara A. Effect of genetic variation of NAT2 on isoniazid and SLCO1B1 and CES2 on rifampin pharmacokinetics in Ghanaian children with tuberculosis. Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e02099-17. doi: 10.1128/AAC.02099-17. Print 2018 Mar. PMID: 29263072.
Rivera SM, Slovak JE, Court MH, Villarino NF. Simultaneous determination of mycophenolic acid and its glucuronide and glycoside derivatives in canine and feline plasma by UHPLC-UV. Biomed Chromatogr. 2017 Aug;31(8). doi: 10.1002/bmc.3942. Epub 2017 Feb 27. PMID: 28146301.
Slovak JE, Rivera SM, Hwang JK, Court MH, Villarino NF. Pharmacokinetics of mycophenolic acid after intravenous administration of mycophenolate mofetil to healthy cats. J Vet Intern Med. 2017 Nov;31(6):1827-1832. PMID: 28892209.
Papageorgiou I, Court MH. Identification and validation of the microRNA response elements in the 3'-untranslated region of the UDP glucuronosyltransferase (UGT) 2B7 and 2B15 genes by a functional genomics approach. Biochem Pharmacol. 2017 Dec 15;146:199-213. PMID: 28962835.
Haines JM, Lee PM, Hegedus RM, Hwang JK, Court MH. Establishment of reference ranges and evaluation of in vitro concentration-dependent platelet inhibition by acetylsalicylic acid for multiple electrode impedance aggregometry in healthy dogs. J Vet Pharmacol Ther. 2017 Dec;40(6):618-628. PMID: 28387027.
Guzman DS, Court MH, Zhu Z, Summa N, Paul-Murphy JR. Pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots (Amazona ventralis). J Avian Med Surg. 2017 Sep;31(3):219-224. PMID: 28891702.
Court MH, Zhu Z, Masse G, Duan SX, James LP, Harmatz JS, Greenblatt DJ. Race, gender, and genetic polymorphism contribute to variability in acetaminophen pharmacokinetics, metabolism, and protein-adduct concentrations in healthy African-American and European-American volunteers. J Pharmacol Exp Ther. 2017 Sep;362(3):431-440. PMID: 28663312
Papageorgiou I, Court MH. Identification and validation of microRNAs directly regulating the UDP-glucuronosyltransferase 1A subfamily enzymes by a functional genomics approach. Biochem Pharmacol. 2017 Aug 1; 137:93-106. PMID: 28433553
Lyngby JG, Court MH, Lee PM. Validation of a method for quantitation of the clopidogrel active metabolite, clopidogrel, clopidogrel carboxylic acid, and 2-oxo-clopidogrel in feline plasma. J Vet Cardiol. 2017 Aug;19(4):384-395. PMID: 28602635
Lewis RS, Fidel J, Dassanayake S, Court MH, Burke NS, Mealey KL. Comparison of chemotherapeutic drug resistance in cells transfected with canine ABCG2 or feline ABCG2. Vet Comp Oncol. 2017 Jun;15(2):411-420. PMID:26464002
Slovak JE, Mealey K, Court MH. Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes. J Vet Pharmacol Ther. 2017 Apr;40(2):123-129. PMID: 27301298.
Perez TE, Mealey KL, Burke NS, Grubb TL, Court MH, Greene SA. Relationship between the melanocortin-1 receptor (MC1R) variant R306ter and physiological responses to mechanical or thermal stimuli in Labrador Retriever dogs. Vet Anaesth Analg. 2017 Mar;44(2):370-374. PMID: 28214221
Court MH, Robbins AH, Whitford AM, Beck EV, Tseng FS, Reeder DM. Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. Am J Vet Res. 2017 Jan;78(1):90-99. PMID: 28029293.
Street CM, Zhu Z, Finel M, Court MH. Bisphenol-A glucuronidation in human liver and breast: identification of UDP-glucuronosyltransferases (UGTs) and influence of genetic polymorphisms. Xenobiotica. 2017 Jan;47(1):1-10. PMID: 26999266.
Rivera Vélez SM, Morassi A, Court MH, Slovak JE, Villarino NF. Development and validation of an ultrafast chromatographic method for quantification of the immunosuppressant mycophenolic acid in canine, feline and human plasma. J Pharm Biomed Anal. 2016 Nov 30;131:94-102. PMID: 27552122.
Perez Jimenez TE, Mealey KL, Grubb TL, Greene SA, Court MH. Tramadol metabolism to O-desmethyl tramadol (M1) and N-desmethyl tramadol (M2) by dog liver microsomes: Species comparison and identification of responsible canine cytochrome P-450s (CYPs). Drug Metab Dispos. 2016 Oct 6; 44 (12) 1963-1972. PMID: 27758804
Papageorgiou I, Freytsis M, Court MH. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver. Biochem Pharmacol. 2016 Oct 1;117:78-87. PMID: 27531059.
Redmon JM, Shrestha B, Cerundolo R, Court MH. Soy isoflavone metabolism in cats compared with other species: urinary metabolite concentrations and glucuronidation by liver microsomes. Xenobiotica. 2016 May;46(5):406-15. PMID: 26366946.
Court MH, Almutairi FE, Greenblatt DJ, Hazarika S, Sheng H, Klein K, Zanger UM, Bourgea J, Patten CJ, Kwara A. Isoniazid mediates the CYP2B6*6 genotype-dependent interaction between efavirenz and antituberculosis drug therapy through mechanism-based inactivation of CYP2A6. Antimicrob Agents Chemother. 2014 Jul;58(7):4145-52. PMID: 24820076.
Court MH, Peter I, Hazarika S, Vasiadi M, Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos. 2014 Jan;42(1):28-32. PMID: 24104197.
Court MH. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Vet Clin North Am Small Anim Pract. 2013 Sep;43(5):1039-54. PMID: 23890237.
Court MH. Canine cytochrome P-450 pharmacogenetics. Vet Clin North Am Small Anim Pract. 2013 Sep;43(5):1027-38. PMID: 23890236.
Yasar U, Greenblatt DJ, Guillemette C, Court MH. Evidence for regulation of UDP-glucuronosyltransferase (UGT) 1A1 protein expression and activity via DNA methylation in healthy human livers. J Pharm Pharmacol. 2013 Jun;65(6):874-83. PMID: 23647681.
Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S, Duan SX, Greenblatt DJ, Lee WM. The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. J Pharmacol Exp Ther. 2013 May;345(2):297-307. PMID: 23408116.
Shrestha B, Reed JM, Starks PT, Kaufman GE, Goldstone JV, Roelke ME, O'Brien SJ, Koepfli KP, Frank LG, Court MH. Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: Phylogenetic timing and the role of hypercarnivory. PLoS One. 2011 Mar 28;6(3):e18046.
Mosher CM, Court MH. Comparative and veterinary pharmacogenomics. Handb Exp Pharmacol. 2010;199:49-77.
He X, Hesse LM, Hazarika S, Masse G, Harmatz JS, Greenblatt DJ, Court MH. Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion. Br J Clin Pharmacol. 2009 Nov;68(5):721-30.
Kwara A, Lartey M, Sagoe KW, Kenu E, Court MH. CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients. AIDS. 2009 Oct 23;23(16):2101-6.
Kwara A, Lartey M, Boamah I, Rezk NL, Oliver-Commey J, Kenu E, Kashuba AD, Court MH. Interindividual Variability in Pharmacokinetics of Generic Nucleoside Reverse Transcriptase Inhibitors in TB/HIV-Coinfected Ghanaian Patients: UGT2B7*1c Is Associated With Faster Zidovudine Clearance and Glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
Kwara A, Lartey M, Sagoe KW, Rzek NL, Court MH. CYP2B6 (c.516G>T) and CYP2A6 (*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients. Br J Clin Pharmacol. 2009 Apr;67(4):427-36.
Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP-glucuronosyltransferase (UGT) 1A6 pharmacogenetics: 1. Identification of polymorphisms in the 5’-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther. 2005 Mar; 313(3):1331-1339.
Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP-glucuronosyltransferase (UGT) 1A6 pharmacogenetics: 2. Structure-function studies of recombinant UGT1A6 amino acid variants. J Pharmacol Exp Ther. 2005 Mar; 313(3):1340-1346.
Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, Von Moltke LL, Greenblatt DJ: UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther. 2004 Aug;310(2):656-65.
Hay Kraus BL, Greenblatt DJ, Venkatakrishnan K, Court MH: Evidence for propofol hydroxylation by cytochrome P450 2B11 in canine liver microsomes: Dog breed and gender differences. Xenobiotica 30(6):575-588, 2000.
Court MH and Greenblatt DJ: Molecular genetic basis for deficient glucuronidation of acetaminophen in cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms Pharmacogenetics 10:355-369, 2000.
Court MH, Hay Kraus BL, Hill DW, Kind AJ and Greenblatt DJ: Propofol hydroxylation by dog liver microsomes: Assay development and dog breed differences. Drug Metabolism and Disposition 27(11):1293-1299, 1999.
Court MH: Anesthesia of the sighthound. Clinical Techniques in Small Animal Practice 14(1): 38-43, 1999.