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
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. Another major project involves identifying and characterizing microRNAs that determine interindividual variability in drug glucuronidation in human liver.
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 Aug 13. pii: S0006-2952(16)30232-5. doi: 10.1016/j.bcp.2016.08.014. [Epub ahead of print] PMID: 27531059
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. 2016 Jun 15. doi: 10.1111/jvp.12338. [Epub ahead of print] PMID: 27301298.
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. 2016 Mar 21:1-10. [Epub ahead of print] PMID: 26999266.
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.