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 supervision

Research expertise

  • Biochemistry and cell biology
  • Pharmacology and pharmaceutical sciences

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.

Supervisory interests

  • Drug metabolising enzymes, cytochrome P450 and UDP-glucuronosyltransferase
  • Gene expression
  • MicroRNA-regulated gene expression

RHD research supervision

Current

Principal supervisor: Molecular Pharmacology (3);

Publications

Book chapters
Mackenzie, P.I., Gardner-Stephen, D.A. and Miners, J.O. (2010). UDP-Glucuronosyltransferases. In Charlene A. McQueen, ed. Comprehensive Toxicology. United Kingdom: Elsevier, pp. 413-433. [online]. http://dx.doi.org/10.1016/B978-0-08-046884-6.00420-6.
Refereed journal articles
Mackenzie, P.I., Hu, D.G. and Gardner-Stephen, D.A. (2010). The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors. Drug Metabolism Reviews, 42(1), pp.99-109. [online]. http://dx.doi.org/10.3109/03602530903209544.
Hu, D.G., Gardner-Stephen, D.A., Severi, G., Gregory, P.A., Treloar, J., Giles, G.G., et al. (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), pp.714-722. [online]. http://dx.doi.org/10.1124/mol.110.065953.
Hu, D.G. and 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), pp.425-439. [online]. http://dx.doi.org/10.1124/mol.109.057380.
Gardner-Stephen, D.A. and Mackenzie, P.I. (2008). Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Current Drug Metabolism, 9(5), pp.439-452. [online]. http://dx.doi.org/10.2174/138920008784746409.
Mackenzie, P.I., Rogers, A., Gillis, J.L., Jorgensen, B.R., Miners, J.O. and Meech, R. (2008). Identification of UDP Glycosyltransferase 3A1 as a UDP N-Acetylglucosaminyltransferase. Journal of Biological Chemistry, 283(52), pp.36205-36210. [online]. http://dx.doi.org/10.1074/jbc.M807961200.
Gardner-Stephen, D.A. and 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), pp.25-36. [online]. http://dx.doi.org/10.1097/FPC.0b013e32801112b5.
Mackenzie, P.I., Bock, K.W., Burchell, B., Guillemette, C., Iyanagi, T., Miners, J.O., et al. (2005). Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenetics and Genomics, 15(10), pp.677-685.
Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A. and 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), pp.953-963. [online]. http://dx.doi.org/10.1124/mol.65.4.953.
Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Duncliffe, K.N. and 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), pp.36107-36114. [online]. http://dx.doi.org/10.1074/jbc.M305565200.

Show all publications

Book chapters
Mackenzie, P.I., Gardner-Stephen, D.A. and Miners, J.O. (2010). UDP-Glucuronosyltransferases. In Charlene A. McQueen, ed. Comprehensive Toxicology. United Kingdom: Elsevier, pp. 413-433. [online]. http://dx.doi.org/10.1016/B978-0-08-046884-6.00420-6.
Miners, J.O., Polasek, T.M., Mackenzie, P.I. and Knights, K.M. (2010). The In Vitro Characterization of Inhibitory Drug-Drug Interactions Involving UDP-Glucuronosyltransferase. In K. Sandy Pang, A. David Rodrigues, Raimund M. Peter, ed. Enzyme- and Transporter-Based Drug-Drug Interactions. New York, USA: Springer, pp. 217-236. [online]. http://dx.doi.org/10.1007/978-1-4419-0840-7_8.
Radominska-Pandya, A., Mackenzie, P.I. and Xie, W. (2004). Transciptional Regulation of UDP-Glucuronosyltransferases. In Lawrence H. Lash, ed. DRUG METABOLISM AND TRANSPORT: MOLECULAR METHODS AND MECHANISMS. Totowa, New Jersey: Humana Press, pp. 133-172.
Refereed journal articles
Rowland, A., Miners, J. and Mackenzie, P. (2013). The UDP-Glucuronosyltransferases: their role in drug metabolism and detoxification. International Journal of Biochemistry and Cell Biology. International Journal of Biochemistry and Cell Biology, 45(6), pp.1121-1132. [online]. http://dx.doi.org/10.1016/j.biocel.2013.02.019.
Zhang, H., Patana, A.-S., Mackenzie, P., Ikushiro, S., Goldman, A. and Finel, M. (2012). Human UDP-Glucuronosyltransferase Expression in Insect Cells: Ratio of Active to Inactive Recombinant Proteins and the Effects of a C-Terminal His-Tag on Glucuronidation Kinetics. Drug Metabolism and Disposition, 40(10), pp.1935-1944. [online]. http://dx.doi.org/10.1124/dmd.112.046086.
Meech, R., Rogers, A., Zhuang, L., Lewis, B., Miners, J. and Mackenzie, P. (2012). Identification of Residues That Confer Sugar Selectivity to UDP-Glycosyltransferase 3A (UGT3A) Enzymes. Journal of Biological Chemistry, 287(29), pp.24122-24130. [online]. http://dx.doi.org/10.1074/jbc.M112.343608.
Meech, R., Miners, J., Lewis, B. and Mackenzie, P. (2012). The glycosidation of xenobiotics and endogenous compounds: Versatility and redundancy in the UDP glycosyltransferase superfamily. Pharmacology and Therapeutics, 134(2), pp.200-218. [online]. http://dx.doi.org/10.1016/j.pharmthera.2012.01.009.
Korprasertthaworn, P., Rowland, A., Lewis, B., Mackenzie, P., Yoovathaworn, K. and Miners, J. (2012). Effects of amino acid substitutions at positions 33 and 37 on UDP-glucuronosyltransferase 1A9 (UGT1A9) activity and substrate selectivity. Biochemical Pharmacology, 84(11), pp.1511-1521. [online]. http://dx.doi.org/10.1016/j.bcp.2012.08.026.
Ishii, Y., Iida, N., Mackenzie, P. and Yamada, H. (2012). Inhibition of Morphine Glucuronidation in the Liver Microsomes of Rats and Humans by Monoterpenoid Alcohols. Biological and Pharmaceutical Bulletin, 35(10), pp.1811-1817. [online]. http://dx.doi.org/10.1248/bpb.b12-00568.
Lewis, B., Mackenzie, P. and Miners, J. (2011). Homodimerization of UDP-glucuronosyltransferase 2B7 (UGT2B7) and identification of a putative dimerization domain by protein homology modeling. Biochemical Pharmacology, 82, pp.2016-2023. [online]. http://dx.doi.org/10.1016/j.bcp.2011.09.007.
Lewis, B., Mackenzie, P. and Miners, J. (2011). Application of Homology Modeling to Generate CYP1A1 Mutants with Enhanced Activation of the Cancer Chemotherapeutic Prodrug Dacarbazine. Molecular Pharmacology, 80(5), pp.879-888. [online]. http://dx.doi.org/10.1124/mol.111.072124.
Mackenzie, P.I., Rogers, A., Elliot, D.J., Chau, N., Hulin, J.-A., Miners, J.O., et al. (2011). The novel UDP glycosyltransferase 3A2: cloning, catalytic properties, and tissue distribution. Molecular Pharmacology, 79(3), pp.472-478. [online]. http://dx.doi.org/10.1124/mol.110.069336.
Meech, R. and Mackenzie, P.I. (2010). UGT3A: novel UDP-glycosyltransferases of the UGT superfamily. Drug Metabolism Reviews, 42(1), pp.45-54. [online]. http://dx.doi.org/10.3109/03602530903205823.
Miners, J.O., Mackenzie, P.I. and 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), pp.196-208. [online]. http://dx.doi.org/10.3109/03602530903210716.
Mackenzie, P.I., Hu, D.G. and Gardner-Stephen, D.A. (2010). The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors. Drug Metabolism Reviews, 42(1), pp.99-109. [online]. http://dx.doi.org/10.3109/03602530903209544.
Ismail, S., Hanapi, N.A., Halim, M.R.A., Uchaipichat, V.N. and Mackenzie, P.I. (2010). Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms. Molecules, 15, pp.3578-3592. [online]. http://dx.doi.org/10.3390/molecules15053578.
Hu, D.G. and 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), pp.2105-2109. [online]. http://dx.doi.org/ 10.1124/dmd.110.035436.
Hu, D.G., Gardner-Stephen, D.A., Severi, G., Gregory, P.A., Treloar, J., Giles, G.G., et al. (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), pp.714-722. [online]. http://dx.doi.org/10.1124/mol.110.065953.
Hu, D.G. and 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), pp.425-439. [online]. http://dx.doi.org/10.1124/mol.109.057380.
Kerdpin, O., Mackenzie, P.I., Bowalgaha Ralalage, K.W., Finel, M. and 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), pp.1948-1955. [online]. http://dx.doi.org/10.1124/dmd.109.028225.
Rowland, A., Knights, K.M., Mackenzie, P.I. and 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), pp.1395-1403. [online]. http://dmd.aspetjournals.org/cgi/content/full/37/7/1395.
Takeda, S., Ishii, Y., Iwanaga, M., Nurrochmad, A., Ito, Y., Mackenzie, P.I., et al. (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), pp.956-964. [online]. http://dx.doi.org/10.1124/mol.108.052001.
Sorich, M.J., Smith, P.A., Miners, J.O., Mackenzie, P.I. and McKinnon, R. (2008). Recent advances in the in silico modelling of UDP Glucuronosyltransferase Substrates. Current Drug Metabolism, 9(1), pp.60-69. [online]. http://dx.doi.org/10.2174/138920008783331167.
Uchaipichat, V.N., Galetin, A., Houston, J., Mackenzie, P.I., Williams, A. and 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), pp.1152-1162. [online]. http://dx.doi.org/10.1124/mol.108.048645.
Rowland, A., Elliot, D.J., Knights, K.M., Mackenzie, P.I. and 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), pp.870-877. [online]. http://dx.doi.org/10.1124/dmd.107.019885.
Mackenzie, P.I., Rogers, A., Gillis, J.L., Jorgensen, B.R., Miners, J.O. and Meech, R. (2008). Identification of UDP Glycosyltransferase 3A1 as a UDP N-Acetylglucosaminyltransferase. Journal of Biological Chemistry, 283(52), pp.36205-36210. [online]. http://dx.doi.org/10.1074/jbc.M807961200.
Itaaho, K., Mackenzie, P.I., Ikushiro, S., Miners, J.O. and 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), pp.2307-2315. [online]. http://dx.doi.org/10.1124/dmd.108.022731.
Gardner-Stephen, D.A. and Mackenzie, P.I. (2008). Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Current Drug Metabolism, 9(5), pp.439-452. [online]. http://dx.doi.org/10.2174/138920008784746409.
Rowland, A., Knights, K.M., Mackenzie, P.I. and 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), pp.1056-1062. [online]. http://dx.doi.org/10.1124/dmd.108.021105.
Bowalgaha, K., Elliot, D.J., Mackenzie, P.I., Knights, K.M. and 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), pp.363-370. [online]. http://dx.doi.org/10.1124/dmd.106.013052.
Gardner-Stephen, D.A. and 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), pp.25-36. [online]. http://dx.doi.org/10.1097/FPC.0b013e32801112b5.
Gardner-Stephen, D.A. and 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), pp.116-120. [online]. http://dx.doi.org/10.1124/dmd.106.012203.
Ishii, Y., Iwanaga, M., Nishimura, Y., Takeda, S., Ikushiro, S., Nagata, K., et al. (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), pp.367-376. [online]. http://www.jstage.jst.go.jp/browse/dmpk.
Kubota, T., Lewis, B.C., Elliot, D.J., Mackenzie, P.I. and 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), pp.1054-1062. [online]. http://dx.doi.org/10.1124/mol.107.037952.
Kurkela, M., Patana, A.-S., Mackenzie, P.I., Court, M.H., Tate, C.G., Hirvonen, J., et al. (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), pp.115-126. [online]. http://dx.doi.org/10.1097/fpc.0b013e328011b598.
Lewis, B.C., Mackenzie, P.I. and 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), pp.58-69. [online]. http://dx.doi.org/10.1016/j.abb.2007.09.014.
Lewis, B.C., Mackenzie, P.I., Elliot, D.J., Burchell, B., Bhasker, R. and 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), pp.1463-1473. [online]. http://dx.doi.org/10.1016/j.bcp.2006.12.021.
Nishimura, Y., Maeda, S., Ikushiro, S., Mackenzie, P.I., Ishii, Y. and 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), pp.1557-1566. [online]. http://dx.doi.org/10.1016/j.bbagen.2007.07.011.
Rowland, A., Gaganis, P., Elliot, D.J., Mackenzie, P.I., Knights, K.M. and 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), pp.137-147. [online]. http://dx.doi.org/10.1124/jpet.106.118216.
Southwood, H., DeGraaf, Y., Mackenzie, P.I., Miners, J.O., Burcham, P. and 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), pp.1520-1527. [online]. http://dx.doi.org/10.1021/tx700188x.
Udomuksorn, W., Elliot, D.J., Lewis, B.C., Mackenzie, P.I., Yoovathaworn, K. and 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), pp.1017-1029. [online]. http://dx.doi.org/10.1097/FPC.0b013e328256b1b6.
Rowland, A., Elliot, D.J., Williams, A., Mackenzie, P.I., Dickinson, R.G. and Miners, J.O. (2006). In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug Metabolism and Disposition, 34(6), pp.1055-1062. [online]. http://dx.doi.org/10.1124/dmd.106.009340.
Okamura, K., Ishii, Y., Ikushiro, S., Mackenzie, P.I. and Yamada, H. (2006). Fatty acyl-CoA as an endogenous activator of UDP-glucuronosyltransferases. Biochemical and Biophysical Research Communications, 345(4), pp.1649-1656. [online]. http://dx.doi.org/10.1016/j.bbrc.2006.05.089.
Miners, J.O., Knights, K.M., Houston, J.B. and 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), pp.1531-1539. [online]. http://dx.doi.org/10.1016/j.bcp.2005.12.019.
Kerdpin, O., Elliot, D.J., Mackenzie, P.I. and Miners, J.O. (2006). Sulfinpyrazone C-Glucuronidation Is Catalyzed Selectively by Human UDP-Glucuronosyltransferase 1A9. Drug Metabolism and Disposition, 34(12), pp.1950-1953. [online]. http://dx.doi.org/10.1124/dmd.106.012385.
Uchaipichat, V.N., Winner, L., Mackenzie, P.I., Elliot, D.J., Williams, A. and 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), pp.427-439. [online]. http://dx.doi.org/10.1111/j.1365-2125.2006.02588.x.
Boyd, M.A., Srasuebkul, P., Ruxrungtham, K., Mackenzie, P.I., Uchaipichat, V.N., Stek, M., 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), pp.321-329. [online]. http://dx.doi.org/10.1097/01.fpc.0000197465.14340.d4.
Takeda, S., Kitajima, Y., Ishii, Y., Nishimura, Y., Mackenzie, P.I., Oguri, K., et al. (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), pp.1277-1282. [online]. http://dx.doi.org/10.1124/dmd.106.009738.
Uchaipichat, V.N., Mackenzie, P.I., Elliot, D.J. and 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), pp.449-456. [online]. http://dx.doi.org/10.1124/dmd.105.007369.
Gregory, P., Gardner-Stephen, D.A., Rogers, A., Michael, M.Z. and 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), pp.527-536. [online]. http://dx.doi.org/10.1097/01.fpc.0000215068.06471.35.
Mackenzie, P.I., Gregory, P.A., Lewinsky, R., Yasmin, S.N., Height, T., MacKinnon, R.A., et al. (2005). Polymorphic variations in the expression of the chemical detoxifying UDP glucuronosytransferases. Toxicology and Applied Pharmacology, 207(Issue 2 SUPPL.), pp.S77-S83. [online]. http://dx.doi.org/10.1016/j.taap.2004.12.026.
Mackenzie, P.I., Bock, K.W., Burchell, B., Guillemette, C., Iyanagi, T., Miners, J.O., et al. (2005). Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenetics and Genomics, 15(10), pp.677-685.
Lewinsky, R., Smith, P. and Mackenzie, P.I. (2005). Glucuronidation of bioflavonoids by human UGT1A10: structure-function relationships. Xenobiotica, 35(2), pp.117-129. [online]. http://dx.doi.org/10.1080/00498250400028189.
Gardner-Stephen, D.A., Gregory, P. and Mackenzie, P.I. (2005). Identification and characterization of functional hepatocyte nuclear factor 1-binding sites in UDP-glucuronosyltransferase genes. Methods in Enzymology, 400(2), pp.22-46. [online]. http://dx.doi.org/10.1016/S0076-6879(05)00002-9.
Finel, M., Li, X., Gardner-Stephen, D.A., Bratton, S., Mackenzie, P.I. and Radominska-Pandya, A. (2005). Human UDP-glucuronosyltransferase 1A5: indentification, expression and activity. Journal of Pharmacology and Experimental Therapeutics, 315(3), pp.1143-1149. [online]. http://dx.doi.org/10.1124/jpet.105.091900.
Bowalgaha Ralalage, K.W., Elliot, D.J., Mackenzie, P.I., Knights, K.M., Swedmark, S. and 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), pp.423-433. [online]. http://dx.doi.org/10.1111/j.1365-2125.2005.02446.x.
Takeda, S., Ishii, Y., Iwanaga, M., Mackenzie, P.I., Nagata, K., Yamazoe, Y., et al. (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), pp.665-672. [online]. http://dx.doi.org/10.1124/mol.104.007641.
Takeda, S., Ishii, Y., Mackenzie, P.I., Nagata, K., Yamazoe, Y., Oguri, K., et al. (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), pp.2026-2027. [online]. http://dx.doi.org/10.1248/bpb.28.2026.
Gardner-Stephen, D.A., Heydel, J.M., Goyal, A., Lu, Y., Xie, W., Lindblom, T., et al. (2004). Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug Metabolism and Disposition, 32(3), pp.340-347. [online]. http://dx.doi.org/10.1124/dmd.32.3.340.
Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A. and 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), pp.953-963. [online]. http://dx.doi.org/10.1124/mol.65.4.953.
Gregory, P., Lewinsky, R.H., Gardner-Stephen, D.A. and Mackenzie, P.I. (2004). Regulation of UDP-glucuronosyltransferases in the gastrointestinal tract. Toxicology and Applied Pharmacology, 199(3), pp.354-363. [online]. http://dx.doi.org/10.1016/j.taap.2004.01.008.
Miners, J.O., Smith, P.A., Sorich, M.J., McKinnon, R.A. and Mackenzie, P.I. (2004). Predicating Human Drug Glucuronidation Parameters: Application of In Vitro and InSilico Modeling Approaches. Annual Review of Pharmacology and Toxicology, 44, pp.1-25. [online]. http://dx.doi.org/10.1146/annurev.pharmtox.44.101802.121546.
Oguri, T., Takahashi, T., Miyazaki, M., Isobe, T., Kohno, N., Mackenzie, P.I., et al. (2004). UGT1A10 is responsible for SN-38 glucuronidation and its expression in human lung cancers. Anticancer Research, 24(5 A), pp.2893-2896. [online]. http://ar.iiarjournals.org/content/24/5A/2893.abstract.
Uchaipichat, V.N., Mackenzie, P.I., Guo, X.H., Gardner-Stephen, D.A., Galetin, A., Houston, J.B., et al. (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), pp.413-423. [online]. http://dx.doi.org/10.1124/dmd.32.4.413.
Wells, P.G., Mackenzie, P.I., Chowdhury, J.R., Guillemette, C., Gregory, P., Ishii, Y., et al. (2004). Glucuronidation and the UDP-glucuronosyltransferases in health and disease. Drug Metabolism and Disposition, 32(3), pp.281-290. [online]. http://dx.doi.org/10.1124/dmd.32.3.281.
Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Duncliffe, K.N. and 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), pp.36107-36114. [online]. http://dx.doi.org/10.1074/jbc.M305565200.
Stone, A.N., Mackenzie, P.I., Galetin, A., Houston, J.B. and 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), pp.1086-1089. [online]. http://dx.doi.org/10.1124/dmd.31.9.1086.
Mackenzie, P.I., Little, J.M. and Radominska-Pandya, A. (2003). Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7. Biochemical Pharmacology, 65(3), pp.417-421. [online]. http://dx.doi.org/10.1016/S0006-2952(02)01522-8.
Mackenzie, P.I., Gregory, P., Gardner-Stephen, D.A., Lewinsky, R.H., Jorgensen, B.R., Nishiyama, T., et al. (2003). Regulation of UDP glucuronosyltransferase genes. Current Drug Metabolism, 4(3), pp.249-257. [online]. http://dx.doi.org/10.2174/1389200033489442.
Tukey, R.H., Strassburg, C.P. and Mackenzie, P.I. (2002). Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Molecular Pharmacology, 62(3), pp.446-450. [online]. http://dx.doi.org/10.1124/mol.62.3.446.
Miners, J.O., Mackenzie, P.I. and McKinnon, R.A. (2002). Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology, 181-182, pp.453-456. [online]. http://dx.doi.org/10.1016/S0300-483X(02)00449-3.
Gregory, P. and 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), pp.154-161. [online]. http://dx.doi.org/10.1124/mol.62.1.154.
Court, M.H., Duan, S.X., Von Moltke, L.L., Greenblatt, D.J., Patten, C.J., Miners, J.O., et al. (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), pp.998-1006.

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