Prof Peter Mackenzie

Professor Peter Ian Mackenzie
Position/s:NHMRC Senior Principal Research Fellow and Professor
Clinical Pharmacology
Phone: +61 8 82045394
Email:
Location: School of Medicine (6D:310.1)
Postal address: GPO Box 2100, Adelaide 5001, South Australia

Biography

Professor Mackenzie was awarded a PhD from the University of Sydney (Biochemistry Department, 1976). He held post doctoral positions at the University of Kuopio, Finland (Physiology Department, 1976-1980), National Institutes of Health, Maryland, USA (NICHD, 1980-1987) before returning to Flinders University (Clinical Pharmacology) in 1987 as a NHMRC Research Fellow. He is currently a NHMRC Senior Principal Research Fellow in the Department.

Qualifications

B.SC (hons 1)
PhD

Honours, awards and grants

  • Awarded Fogarty International Fellowship for postdoctoral studies at the National Institutes of Health USA (1980-1983) appointed visiting associate in 1983 and visiting scientist in 1986.
  • Awarded NHMRC Fellowship (1987), SRF (1991), PRF (1994), SPRF (2000).
  • Awarded UICC International Cancer Research Fellowship (1993).
  • Elected ASCEPT visitor to the British Toxicological Society, 2000.
  • Honoured as the 11th Dr Chiravat Sodavongvivad Memorial Lecturer to the Thai Pharmacological Society, Chiangmai, Thailand in 2004.
  • Awarded the Asia/Pacific Scientific Achievement Award for 2006 from the International Society for the Study of Xenobiotics, 2006.
  • Awarded the RAND MEDAL for 2009 by ASCEPT.

Key responsibilities

  • Research only
  • Honours and Postgraduate research supervision

Research and consultancy

Research interests

Our defense against the toxic effects of small organic molecules is mediated by families of enzymes found in the internal membranes of cells. Many small organic molecules, such as environmental pollutants, carcinogens and therapeutic drugs, are fat-soluble and will accumulate in the body to toxic levels unless they are modified, usually by the addition of sugar groups. The modified chemical, in the majority of cases, is less toxic and readily removed from the body. We have identified and characterized many of the sugar-transferring enzymes involved in this detoxification process. We are investigating how these enzymes are controlled in the cell and whether there are genetic differences in control processes that may impact on our ability to detoxify drugs and chemicals. This research may provide strategies to help reduce the risk of chemical-induced carcinogenesis and hormone-dependent cancers, such as those of the prostate and breast.

Publications

Book chapters

Mackenzie, P.I., Gardner-Stephen, D.A., & Miners, J.O., 2010. UDP-Glucuronosyltransferases. In Comprehensive Toxicology. United Kingdom: Elsevier, pp. 413-433.

Refereed journal articles

Mackenzie, P.I., Hu, D., & Gardner-Stephen, D.A., 2010. The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors. Drug Metabolism Reviews, 42(1), 99-109.

Hu, D., Gardner-Stephen, D.A., Severi, G., Gregory, P.A., Treloar, J., Giles, G.G., English, D., Hopper, J.L., Tilley, W., & Mackenzie, P.I., 2010. A Novel Polymorphism in a Forkhead Box A1 (FOXA1) Binding Site of the Human UDP Glucuronosyltransferase 2B17 Gene Modulates Promoter Activity and is associated with altered levels of circulating Androstane-3{alpha},17{beta}-diol Glucuronide. Molecular Pharmacology, 78(4), 714-722.

Hu, D. & Mackenzie, P.I., 2009. Estrogen Receptor {alpha}, Fos-Related Antigen-2, and c-Jun Coordinately Regulate Human UDP Glucuronosyltransferase 2B15 and 2B17 Expression in Response to 17b-Estradiol in MCF-7 cells. Molecular Pharmacology, 76(2), 425-439.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2008. Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Current Drug Metabolism, 9(5), 439-452.

Mackenzie, P.I., Rogers, A., Gillis, J.L., Jorgensen, B.R., Miners, J.O., & Meech, R., 2008. Identification of UDP Glycosyltransferase 3A1 as a UDP N-Acetylglucosaminyltransferase. Journal of Biological Chemistry, 283(52), 36205-36210.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2007. Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4alpha. Pharmacogenetics and Genomics, 17(1), 25-36.

Mackenzie, P.I., Bock, K., Burchell, B., Guillemette, C., Iyanagi, T., Miners, J.O., Owens, I.S., Nerbert, D.W., & Ikushiro, S., 2005. Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenetics and Genomics, 15(10), 677-685.

Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A., & Mackenzie, P.I., 2004. Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9 and 1A10 genes by hepatocyte nuclear factor 1-alpha and the caudal-related homeodomain protein 2. Molecular Pharmacology, 65(4), 953-963.

Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Duncliffe, K.N., & Mackenzie, P.I., 2003. Cloning and characterization of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 gene promoters: differential regulation through an intitiator-like region. Journal of Biological Chemistry, 278(38), 36107-36114.

Show all publications

Book chapters

Mackenzie, P.I., Gardner-Stephen, D.A., & Miners, J.O., 2010. UDP-Glucuronosyltransferases. In Comprehensive Toxicology. United Kingdom: Elsevier, pp. 413-433.

Miners, J.O., Polasek, T.M., Mackenzie, P.I., & Knights, K.M., 2010. The In Vitro Characterization of Inhibitory Drug-Drug Interactions Involving UDP-Glucuronosyltransferase. In Enzyme- and Transporter-Based Drug-Drug Interactions. New York, USA: Springer, pp. 217-236.

Radominska-Pandya, A., Mackenzie, P.I., & Xie, W., 2004. Transciptional Regulation of UDP-Glucuronosyltransferases. In DRUG METABOLISM AND TRANSPORT: MOLECULAR METHODS AND MECHANISMS. Totowa, New Jersey: Humana Press, pp. 133-172.

Refereed journal articles

Meech, R., Miners, J.O., Lewis, B.C., & Mackenzie, P.I., 2012. The glycosidation of xenobiotics and endogenous compounds: Versatility and redundancy in the UDP glycosyltransferase superfamily. PHARMACOLOGY & THERAPEUTICS, 134, 200-218.

Mackenzie, P.I., Rogers, A., Elliot, D.J., Chau, N., Hulin, J., Miners, J.O., & Meech, R., 2011. The novel UDP glycosyltransferase 3A2: cloning, catalytic properties, and tissue distribution. Molecular Pharmacology, 79(3), 472-478.

Mackenzie, P.I., Rogers, A., Elliot, D.J., Chau, N., Hulin, J., Miners, J.O., & Meech, R., 2011. The Novel UDP Glycosyltransferase 3A2: Cloning, Catalytic Properties, and Tissue Distribution. Molecular Pharmacology, 79(3), 472-478.

Lewis, B.C., Mackenzie, P.I., & Miners, J.O., 2011. Homodimerization of UDP-glucuronosyltransferase 2B7 (UGT2B7) and identification of a putative dimerization domain by protein homology modeling. Biochemical Pharmacology, 82, 2016-2023.

Lewis, B.C., Mackenzie, P.I., & Miners, J.O., 2011. Application of Homology Modeling to Generate CYP1A1 Mutants with Enhanced Activation of the Cancer Chemotherapeutic Prodrug Dacarbazine. Molecular Pharmacology, 80(5), 879-888.

Mackenzie, P.I., Hu, D., & Gardner-Stephen, D.A., 2010. The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors. Drug Metabolism Reviews, 42(1), 99-109.

Ismail, S., Hanapi, N.A., Halim, M.R., Uchaipichat, V.N., & Mackenzie, P.I., 2010. Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms. Molecules, 15, 3578-3592.

Miners, J.O., Mackenzie, P.I., & Knights, K.M., 2010. The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential. Drug Metabolism Reviews, 42(1), 196-208.

Meech, R. & Mackenzie, P.I., 2010. UGT3A: novel UDP-glycosyltransferases of the UGT superfamily. Drug Metabolism Reviews, 42(1), 45-54.

Hu, D. & Mackenzie, P.I., 2010. Forkhead Box Protein A1 Regulates UDP-Glucuronosyltransferase 2B15 Gene Transcription in LNCaP Prostate Cancer Cells. Drug Metabolism and Disposition, 38(12), 2105-2109.

Hu, D., Gardner-Stephen, D.A., Severi, G., Gregory, P.A., Treloar, J., Giles, G.G., English, D., Hopper, J.L., Tilley, W., & Mackenzie, P.I., 2010. A Novel Polymorphism in a Forkhead Box A1 (FOXA1) Binding Site of the Human UDP Glucuronosyltransferase 2B17 Gene Modulates Promoter Activity and is associated with altered levels of circulating Androstane-3{alpha},17{beta}-diol Glucuronide. Molecular Pharmacology, 78(4), 714-722.

Rowland, A., Knights, K.M., Mackenzie, P.I., & Miners, J.O., 2009. Characterization of the Binding of Drugs to Human Intestinal Fatty Acid Binding Protein (IFABP): Potential Role of IFABP as an Altenative to Albumin for in Vitro-in Vivo Extrapolation of Drug Kinetic Parameters. Drug Metabolism and Disposition, 37(7), 1395-1403.

Kerdpin, O., Mackenzie, P.I., Bowalgaha Ralalage, K.W., Finel, M., & Miners, J.O., 2009. Influence of N-Terminal Domain Histidine and Proline Residues on the Substrate Selectivities of Human UDP-Glucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10. Drug Metabolism and Disposition, 37(9), 1948-1955.

Hu, D. & Mackenzie, P.I., 2009. Estrogen Receptor {alpha}, Fos-Related Antigen-2, and c-Jun Coordinately Regulate Human UDP Glucuronosyltransferase 2B15 and 2B17 Expression in Response to 17b-Estradiol in MCF-7 cells. Molecular Pharmacology, 76(2), 425-439.

Takeda, S., Ishii, Y., Iwanaga, M., Nurrochmad, A., Ito, Y., Mackenzie, P.I., Nagata, K., Yamazoe, Y., Oguri, K., & Yamada, H., 2009. Interaction of Cytochrome P450 3A4 and UDP-Glucuronosyltransferase 2B7: Evidence for Protein-Protein Association and Possible Involvement of CYP3A4 J-Helix in the Interaction. Molecular Pharmacology, 75(4), 956-964.

Sorich, M.J., Smith, P.A., Miners, J.O., Mackenzie, P.I., & McKinnon, R.A., 2008. Recent advances in the in silico modelling of UDP Glucuronosyltransferase Substrates. Current Drug Metabolism, 9(1), 60-69.

Uchaipichat, V.N., Galetin, A., Houston, J., Mackenzie, P.I., Williams, A., & Miners, J.O., 2008. Kinetic modeling of the interactions between 4-Methylumbelliferone, 1-Naphthol, and zidovudine glucuronidation by UDP-glucuronosyltransferase 2B7 (UGT2B7) provides evidence for multiple substrate binding and effector sites. Molecular Pharmacology, 74(4), 1152-1162.

Rowland, A., Knights, K.M., Mackenzie, P.I., & Miners, J.O., 2008. The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities. Drug Metabolism and Disposition, 36(6), 1056-1062.

Rowland, A., Elliot, D.J., Knights, K.M., Mackenzie, P.I., & Miners, J.O., 2008. The "Albumin Effect" and in Vitro-in Vivo Extrapolation: Sequestration of Long-Chain Unsaturated Fatty Acids Enhances Phenytoin Hydroxylation by Human Liver Microsomal and Recombinant Cytochrome P450 2C9. Drug Metabolism and Disposition, 36(5), 870-877.

Mackenzie, P.I., Rogers, A., Gillis, J.L., Jorgensen, B.R., Miners, J.O., & Meech, R., 2008. Identification of UDP Glycosyltransferase 3A1 as a UDP N-Acetylglucosaminyltransferase. Journal of Biological Chemistry, 283(52), 36205-36210.

Itaaho, K., Mackenzie, P.I., Ikushiro, S., Miners, J.O., & Finel, M., 2008. The configuration of the 17-hydroxy group variably influences the glucuronidation of B-estradiol and epiestradiol by human UDP-Glucuronosyltransferases. Drug Metabolism and Disposition, 36(11), 2307-2315.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2008. Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Current Drug Metabolism, 9(5), 439-452.

Ishii, Y., Iwanaga, M., Nishimura, Y., Takeda, S., Ikushiro, S., Nagata, K., Yamazoe, Y., Mackenzie, P.I., & Yamada, H., 2007. Protein-protein interactions between rat hepatic cytochromes P450 (P450s) and UDP-Glucuronosyltransferases (UGTs): evidence for the functionally active UGT in P450-UGT complex. Drug Metabolism and Pharmacokinetics, 22(5), 367-376.

Kubota, T., Lewis, B.C., Elliot, D.J., Mackenzie, P.I., & Miners, J.O., 2007. Critical roles of residues 36 and 40 in the phenol and tertiary amine aglycone substrate selectivities of UDP-glucuronosyltransferases 1A3 and 1A4. Molecular Pharmacology, 72(4), 1054-1062.

Kurkela, M., Patana, A., Mackenzie, P.I., Court, M.H., Tate, C.G., Hirvonen, J., Goldman, A., & Finel, M., 2007. Interactions with other human UDP-glucuronosyltransferases attenuate the consequences of the Y485D mutation on the activity and substrate affinity of UGT1A6. Pharmacogenetics and Genomics, 17(2), 115-126.

Lewis, B.C., Mackenzie, P.I., & Miners, J.O., 2007. Comparative homology modeling of human cytochrome P4501A1 (CYP1A1) and confirmation of residues involved in 7-ethoxyresorufin O-deethylation by site-directed mutagenesis and enzyme kinetic analysis. Archives of Biochemistry and Biophysics, 468(1), 58-69.

Lewis, B.C., Mackenzie, P.I., Elliot, D.J., Burchell, B., Bhasker, R., & Miners, J.O., 2007. Amino terminal domains of human UDP-glucuronosyltransferases (UGT) 2B7 and 2B15 associated with substrate selectivity and autoactivation. Biochemical Pharmacology, 73(9), 1463-1473.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2007. Isolation of the UDP-glucuronosyltransferase 1A3 and 1A4 proximal promoters and characterization of their dependence on the transcription factor hepatocyte nuclear factor 1 alpha. Drug Metabolism and Disposition, 35(1), 116-120.

Rowland, A., Gaganis, P., Elliot, D.J., Mackenzie, P.I., Knights, K.M., & Miners, J.O., 2007. Binding of inhibitory fatty acids is responsible for the enhancement of UDP-Glucuronosyltransferase 2B7 activity by albumin: implications for in vitro-in vivo extrapolation. Journal of Pharmacology and Experimental Therapeutics, 321(1), 137-147.

Southwood, H., DeGraaf, Y., Mackenzie, P.I., Miners, J.O., Burcham, P., & Sallustio, B., 2007. Carboxylic Acid Drug-Induced DNA Nicking in HEK293 Cells Expressing Human UDP-Glucuronosyltransferases: Role of Acyl Glucuronide Metabolites and Glycation Pathways. Chemical Research in Toxicology, 20(10), 1520-1527.

Udomuksorn, W., Elliot, D.J., Lewis, B.C., Mackenzie, P.I., Yoovathaworn, K., & Miners, J.O., 2007. Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenetics and Genomics, 17(12), 1017-1029.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2007. Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4alpha. Pharmacogenetics and Genomics, 17(1), 25-36.

Bowalgaha, K.W., Elliot, D.J., Mackenzie, P.I., Knights, K.M., & Miners, J.O., 2007. The glucuronidation of delta4-3-keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6alpha- and 21-hydroxyprogesterone are selective substrates for UGT2B7. Drug Metabolism and Disposition, 35(3), 363-370.

Nishimura, Y., Maeda, S., Ikushiro, S., Mackenzie, P.I., Ishii, Y., & Yamada, H., 2007. Inhibitory effects of adenine nucleotides and related substances on UDP-glucuronosyltransferase: structure-effect relationships and evidence for an allosteric mechanism. Biochimica et Biophysica Acta-General Subjects, 1770(11), 1557-1566.

Boyd, M.A., Srasuebkul, P., Ruxrungtham, K., Mackenzie, P.I., Uchaipichat, V.N., Stek, M., Lange, J.M., Phanuphak, P., Cooper, D.A., Udomuksorn, W., et al., 2006. Relationship between hyperbilirubinaemia and UDP-glucoronosyltransferase 1A1 (UGT1A1) polymorphism in adult HIV-infected Thai patients treated with indinavir. Pharmacogenetics and Genomics, 16(5), 321-329.

Gregory, P., Gardner-Stephen, D.A., Rogers, A., Michael, M.Z., & Mackenzie, P.I., 2006. The caudal-related homeodomain protein Cdx2 and hepatocyte nuclear factor 1-alpha cooperatively regulate the UDP-glucuronosyltransferase 2B7 gene promotor. Pharmacogenetics and Genomics, 16(7), 527-536.

Kerdpin, O., Elliot, D.J., Mackenzie, P.I., & Miners, J.O., 2006. Sulfinpyrazone C-Glucuronidation Is Catalyzed Selectively by Human UDP-Glucuronosyltransferase 1A9. Drug Metabolism and Disposition, 34(12), 1950-1953.

Miners, J.O., Knights, K.M., Houston, J., & Mackenzie, P.I., 2006. In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: Pitfalls and promises. Biochemical Pharmacology, 71(11), 1531-1539.

Okamura, K., Ishii, Y., Ikushiro, S., Mackenzie, P.I., & Yamada, H., 2006. Fatty acyl-CoA as an endogenous activator of UDP-glucuronosyltransferases. Biochemical and Biophysical Research Communications, 345(4), 1649-1656.

Rowland, A., Elliot, D.J., Williams, A., Mackenzie, P.I., Dickinson, R.G., & Miners, J.O., 2006. In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug Metabolism and Disposition, 34(6), 1055-1062.

Takeda, S., Kitajima, Y., Ishii, Y., Nishimura, Y., Mackenzie, P.I., Oguri, K., & Yamada, H., 2006. Inhibition of UDP-glucuronosyltransferase 2B7-catalyzed morphine glucuronidation by Ketoconazole: Dual mechanisms involving a novel non-competitive mode. Drug Metabolism and Disposition, 34(8), 1277-1282.

Uchaipichat, V.N., Mackenzie, P.I., Elliot, D.J., & Miners, J.O., 2006. Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) 'probes' for human UDP-glucuronosyltransferases. Drug Metabolism and Disposition, 34(3), 449-456.

Uchaipichat, V.N., Winner, L., Mackenzie, P.I., Elliot, D.J., Williams, A., & Miners, J.O., 2006. Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation. British Journal of Clinical Pharmacology, 61(4), 427-439.

Gardner-Stephen, D.A., Gregory, P., & Mackenzie, P.I., 2005. Identification and characterization of functional hepatocyte nuclear factor 1-binding sites in UDP-glucuronosyltransferase genes. Methods in Enzymology, 400(2), 22-46.

Finel, M., Li, X., Gardner-Stephen, D.A., Bratton, S., Mackenzie, P.I., & Radominska-Pandya, A., 2005. Human UDP-glucuronosyltransferase 1A5: indentification, expression and activity. Journal of Pharmacology and Experimental Therapeutics, 315(3), 1143-1149.

Bowalgaha Ralalage, K.W., Elliot, D.J., Mackenzie, P.I., Knights, K.M., Swedmark, S., & Miners, J.O., 2005. S-Naproxen and desmethylnaproxen glucuronidation by human liver miscrosomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. British Journal of Clinical Pharmacology, 60(4), 423-433.

Lewinsky, R.H., Smith, P., & Mackenzie, P.I., 2005. Glucuronidation of bioflavonoids by human UGT1A10: structure-function relationships. Xenobiotica, 35(2), 117-129.

Mackenzie, P.I., Bock, K., Burchell, B., Guillemette, C., Iyanagi, T., Miners, J.O., Owens, I.S., Nerbert, D.W., & Ikushiro, S., 2005. Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenetics and Genomics, 15(10), 677-685.

Mackenzie, P.I., Gregory, P., Lewinsky, R.H., Yasmin, S.N., Height, T., MacKinnon, R.A., & Gardner-Stephen, D.A., 2005. Polymorphic variations in the expression of the chemical detoxifying UDP glucuronosytransferases. Toxicology and Applied Pharmacology, 207(Issue 2 SUPPL.), S77-S83.

Takeda, S., Ishii, Y., Iwanaga, M., Mackenzie, P.I., Nagata, K., Yamazoe, Y., Oguri, K., & Yamada, H., 2005. Modulation of UDP-glucuronosyltransferase function by cytochrome P450: Evidence for the alteration of UGT2B7-catalyzed glucuronidation of morphine by CYP3A4. Molecular Pharmacology, 67(3), 665-672.

Takeda, S., Ishii, Y., Mackenzie, P.I., Nagata, K., Yamazoe, Y., Oguri, K., & Yamada, H., 2005. Modulation of UDP-glucuronosyltransferase 2B7 function by cytochrome P450s in vitro: Differential effects of CYP1A2, CYP2C9 and CYP3A4. Biological and Pharmaceutical Bulletin, 28(10), 2026-2027.

Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A., & Mackenzie, P.I., 2004. Regulation of UDP-glucuronosyltransferases in the gastrointestinal tract. Toxicology and Applied Pharmacology, 199(3), 354-363.

Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A., & Mackenzie, P.I., 2004. Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9 and 1A10 genes by hepatocyte nuclear factor 1-alpha and the caudal-related homeodomain protein 2. Molecular Pharmacology, 65(4), 953-963.

Gardner-Stephen, D.A., Heydel, J.M., Goyal, A., Lu, Y., Xie, W., Lindblom, T., Mackenzie, P.I., & Radominska-Pandya, A., 2004. Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug Metabolism and Disposition, 32(3), 340-347.

Miners, J.O., Smith, P.A., Sorich, M.J., McKinnon, R.A., & Mackenzie, P.I., 2004. Predicating Human Drug Glucuronidation Parameters: Application of In Vitro and InSilico Modeling Approaches. Annual Review of Pharmacology and Toxicology, 44, 1-25.

Wells, P.G., Mackenzie, P.I., Chowdhury, J.R., Guillemette, C., Gregory, P., Ishii, Y., Hansen, A.J., Kessler, F.K., Kim, P.M., Chowdhury, N.R., et al., 2004. Glucuronidation and the UDP-glucuronosyltransferases in health and disease. Drug Metabolism and Disposition, 32(3), 281-290.

Uchaipichat, V.N., Mackenzie, P.I., Guo, X.H., Gardner-Stephen, D.A., Galetin, A., Houston, J.B., & Miners, J.O., 2004. Human UDP-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumberlliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metabolism and Disposition, 32(4), 413-423.

Oguri, T., Takahashi, T., Miyazaki, M., Isobe, T., Kohno, N., Mackenzie, P.I., & Fujiwara, Y., 2004. UGT1A10 is responsible for SN-38 glucuronidation and its expression in human lung cancers. Anticancer Research, 24(5 A), 2893-2896.

Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Duncliffe, K.N., & Mackenzie, P.I., 2003. Cloning and characterization of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 gene promoters: differential regulation through an intitiator-like region. Journal of Biological Chemistry, 278(38), 36107-36114.

Mackenzie, P.I., Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Jorgensen, B.R., Nishiyama, T., Xie, W., & Radominska-Pandya, A., 2003. Regulation of UDP glucuronosyltransferase genes. Current Drug Metabolism, 4(3), 249-257.

Mackenzie, P.I., Little, J.M., & Radominska-Pandya, A., 2003. Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7. Biochemical Pharmacology, 65(3), 417-421.

Stone, A.N., Mackenzie, P.I., Galetin, A., Houston, J.B., & Miners, J.O., 2003. Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human UDP-glucuronosyltranferases: evidence for atypical glucuronidation kinetics by UGT2B7. Drug Metabolism and Disposition, 31(9), 1086-1089.

Tukey, R.H., Strassburg, C.P., & Mackenzie, P.I., 2002. Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Molecular Pharmacology, 62(3), 446-450.

Miners, J.O., Mackenzie, P.I., & McKinnon, R.A., 2002. Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology, 181-182, 453-456.

Gregory, P. & Mackenzie, P.I., 2002. The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1 alpha-mediated activation of the UDP-Glucuronosyltransferase 2B17 gene. Molecular Pharmacology, 62(1), 154-161.

Court, M.H., Duan, S.X., Von Moltke, L.L., Greenblatt, D.J., Patten, C.J., Miners, J.O., & Mackenzie, P.I., 2001. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. Journal of Pharmacology and Experimental Therapeutics, 299(3), 998-1006.

Refereed conference papers

Miners, J.O., Rowland, A., Uchaipichat, V.N., Elliot, D.J., Knights, K.M., Galetin, A., Houston, J., & Mackenzie, P.I., 2007. In vitro-in vivo extrapolation of drug glucuronidation kinetic parameters: Pitfalls and Promises. The Taskinen Symposium on Drug Design and Metabolism, 32-35.

Conference publications

Mackenzie, P.I., Rogers, A., Haines, A.Z., Miners, J.O., Gardner-Stephen, D.A., & Meech, R., 2010. Characterization of the Novel UDP Glycosyltransferase 3 Family. Program and Abstract Book, 18th International Symposium on Microsomes and Drug Oxidations, 73-73.

Miners, J.O., Chau, N., Elliot, D.J., & Mackenzie, P.I., 2010. Glucuronidation and Glucosidation are Parallel Metabolic Pathways: Studies with the Model Substrate Morphine. Program and Abstract Book, 18th International Symposium on Microsomes and Drug Oxidations, 75-75.

Mackenzie, P.I., Hu, D., Meech, R., & Gardner-Stephen, D.A., 2009. Transcriptional Control of UDP Glucuonosyltransferases. Drug Metabolism Reviews - Biotransformation and Disposition of Xenobiotics, 41(Suppl. 2), 16-17.

Kerdpin, O., Mackenzie, P.I., Bowalgaha Ralalage, K.W., Finel, M., & Miners, J.O., 2009. Roles of N-Terminal Domain Histidine and Proline Residues in the Substrate Selectivities of Human UDP-Glucuronosyltransferase (UGT) 1A1, 1A6, 1A9, 2B7, and 2B10. Drug Metabolism Reviews - Biotransformation and Disposition of Xenobiotics, 41(Suppl. 2), 70-71.

Ishii, Y., Iwamoto, Y., Oizaki, T., Nurrochmad, A., Nishimura, Y., Ikushiro, S., Taura, F., Morimoto, S., Nagata, K., Yamazoe, Y., et al., 2009. Cytochrome P450 3A4 Enhances UDP-Glucuronosyltransferase 1A9-catalyzed Glucuronidation of SN-38, an Active Metabolite of Irinotecan. Drug Metabolism Reviews - Biotransformation and Disposition of Xenobiotics, 41(Suppl. 2), 69-69.

Mackenzie, P.I., Meech, R., & Miners, J.O., 2009. Characterization of the UDP Glucosyltransferase 3A Family. Drug Metabolism Reviews - Biotransformation and Disposition of Xenobiotics, 41(Suppl. 1), 29-29.

Miners, J.O., Rowland, A., Mackenzie, P.I., & Knights, K.M., 2009. Comparison of the Binding of Drugs to Human Intestinal Fatty Acid Binding Protein and Albumin: Application to In Vitro-In Vivo Extrapolation. Drug Metabolism Reviews - Biotransformation and Disposition of Xenobiotics, 41(Suppl. 1), 60-61.

Mackenzie, P.I. & Gardner-Stephen, D.A., 2008. Differential regulation of UDP Glucuronosyltransferase genes by liver enriched transcription factors. 12th International glucuronidation and UGT workshop, 35-35.

Mackenzie, P.I. & Gardner-Stephen, D.A., 2008. Transcriptional regulation of drug metabolising enzymes: the role of liver enriched transcription factors. Drug Metabolism Reviews, 40(suppl. 2), 18-18.

Miners, J.O., Rowland, A., Mackenzie, P.I., Uchaipichat, V.N., & Knights, K.M., 2008. In vitro-in vivo extrapolation for glucuronidated drugs. 12th International glucuronidation and UGt workshop, 32-32.

Polasek, T.M., Rowland, A., Elliot, D.J., Knights, K.M., Mackenzie, P.I., Polak, S., Rostami-Hodjegan, A., & Miners, J.O., 2008. Incorporating inter-individual variability into the prediction of phenytoin clearance from albumin-adjusted in vitro data. Drug Metabolism Reviews, 40, 51-51.

Gardner-Stephen, D.A., Gillis, J.L., Rogers, A., & Mackenzie, P.I., 2007. Hepatocyte nuclear factor 1 alpha regulates human UDP-glucuronosyltransferase genes via several distinct mechanisms. 2007 Joint Meeting of ASCEPT and SEAWP-RMP, 12, 2-97-2-97.

Elliot, D.J., Rowland, A., Knights, K.M., Mackenzie, P.I., & Miners, J.O., 2007. Effect of albumin on in vitro lignocaine kinetics - revealing the 'true' contribution of CYP1A2. 2007 Joint Meeting of ASCEPT and SEAWP-RMP, 12, 3-51-3-51.

Ishii, Y., Takeda, S., Nurrochmad, A., Iwamoto, Y., Ito, Y., Mackenzie, P.I., Nagata, K., Yamazoe, Y., Oguri, K., & Yamada, H., 2007. Interaction of cytochrome P450 3A4 and UDP-glucuronosyltransferase 2B7: possible involvement of a region located in the J-helix of CYP3A4 in the interaction. Drug Metabolism Reviews: Abstracts from the 8th International ISSX meeting, 39(Suppl. 1), 301-302.

Sallustio, B., Southwood, H., DeGraaf, Y., Mackenzie, P.I., Miners, J.O., & Burcham, P., 2007. Glucuronidation-dependent DNA nicking by carboxylic acid drugs in HEK293 cells expressing human UDP-glucuronosyltransferases. Drug metabolism reviews: Abstracts from the 8th international ISSX meeting, 39(Suppl. 1), 144-145.

Rowland, A., Elliot, D.J., Knights, K.M., Mackenzie, P.I., & Miners, J.O., 2007. Sequestration of long chain unsaturated fatty acids by albumin enhances phenytoin hydroxylation in vitro: implications for clearance prediction. 2007 Joint meeting of ASCEPT and SEAWP-RMP, 12, 1-9-1-9.

Rogers, A. & Mackenzie, P.I., 2007. Expression of UDP-Glucuronosyltransferase 1A1 in the MCF7 breast cancer cell line protects against genotoxic and cytotoxic effects of benzo(alpha)pyrene. 2007 Joint meeting of ASCEPT and SEAWP-RMP, 12, 3-88-3-88.

Miners, J.O., Rowland, A., Uchaipichat, V.N., Elliot, D.J., Knights, K.M., & Mackenzie, P.I., 2007. Unravelling the kinetic anomalies of UDP-glucuronosyltransferases. Drug Metabolism Reviews: Abstracts from the 8th International ISSX Meeting, 39(Suppl. 1), 11-11.

Lewis, B.C., Mackenzie, P.I., & Miners, J.O., 2007. Identification of the cytochrome P4501A1 (CYP1A1) residues involved in 7-ethoxyresorufin o-deethylation. 2007 Joint Meeting of ASCEPT and SEAWP-RMP, 12, 1-6-1-6.

Galetin, A., Uchaipichat, V.N., Mackenzie, P.I., Houston, J., & Miners, J.O., 2006. Multisite kinetic modelling of interactions between UDP-glucuronosyltransferase 2B7 (UGT2B7) substrates. Drug Metabolism Review: Abstracts from the 9th European ISSX Meeting, 38(Supp 1), 45-46.

Gardner-Stephen, D.A., Rogers, A., & Mackenzie, P.I., 2006. Differential regulation of the human UDP-glucuronosyltransferase genes by liver-enriched transcription factors. Proceedings of the Australian Health and Medical Research Congress 2006, 156-156.

Uchaipichat, V.N., Mackenzie, P.I., Houston, J., Galetin, A., & Miners, J.O., 2006. Characterisation of interactions between UDP-glucuronosyltransferase 2B7 (UGT2B7) substrates using multisite kinetic modelling [abstract]. Acta Pharmacologica Sinica: XVth World Congress of Pharmacology - Meeting Abstracts, 27(Supp 1), 218-218.

Rowland, A., Gaganis, P., Elliot, D.J., Mackenzie, P.I., Knights, K.M., & Miners, J.O., 2006. Binding of inhibitory fatty acids contributes to the enhancement of UDP-glucuronosyltransferase. Proceedings of the Australian Health and Medical Research Congress 2006, 402-402.

Mackenzie, P.I., 2006. The UDP glucuronosyltransferase superfamily; our guardian against toxic chemicals. Drug Metobolism Reviews: Abstracts from the 1st Asia Pacific ISSX Meeting, 38(Suppl. 3).

Mackenzie, P.I. & Gardner-Stephen, D.A., 2006. Transcriptional regulation of the UDP glucuronosyltransferase gene family. Drug Metabolism Reviews: Abstracts from the 9th European ISSX Meeting, 38(Suppl.1), 8-8.

Lewis, B.C., Mackenzie, P.I., Elliot, D.J., Burchell, B., Bhasker, R., & Miners, J.O., 2006. Chimeric UDP-Gucluronosyltransferase (UGT) 2B7 and 2B15 proteins define domains associated with substrate selectivity and autoactivation. Acta Pharmacologica Sinica: XVth World Congress of Pharmacology - Meeting Abstracts, 27(Supp1), 214-214.

Udomuksorn, W., Mackenzie, P.I., Lewis, B.C., Elliot, D.J., Yoovathaworn, K., & Miners, J.O., 2006. Coding region mutations in UGT1A1 impair bilirubin and xenobiotic glucuronidation [abstract]. Acta Pharmacologica Sinica: XVth World Congress of Pharmacology - Meeting Abstracts, 27(Supp 1), 210-210.

Lewis, B.C., Mackenzie, P.I., & Miners, J.O., 2005. Homology modeling of cytochrome P4501A1 (CYP1A1). Proceedings: Joint Meeting of ASCEPT and APSA.

Gardner-Stephen, D.A. & Mackenzie, P.I., 2005. Hepatocyte nuclear transcription factors co-operate to regulate the human UDP glucuronosyltransferase 1A9 gene. Joint meeting of ASCEPT and APSA, 11.

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Professional and community engagement

  • Elected member of the American Society of Biochemistry and Molecular Biology in 1987-
  • Elected member of the American Association for the Study of Liver Diseases in 1988-.
  • Fellow of the International Union Against Cancer (UICC) 1995-
  • Councillor of the International Society for the Study of Xenobiotics (ISSX) 1994-1997, 2004-2007
  • Chair of Regional Scientific Affairs Committee (ISSX-Pacific Region) 1993-1997
  • Member of ISSX International Scientific Affairs Committee 1993-1997, Chair, 2008-
  • Appointed to the UDP Glycosyltransferase Nomenclature Committee of the International Union of Biochemistry and Molecular Biology and JUPAC-IUBMB Joint Commission on Biochemical Nomenclature. 1995-
  • Appointed UGT specialist advisor to the HUGO Genome Nomenclature Committee. 2005-



inspiring achievement