Robert Tukey

Title(s)Professor, Pharmacology
SchoolHealth Sciences
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    Collapse Biography 
    Collapse Education and Training
    Ph.D.University of Iowa
    B.S.University of Minnesota

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    Collapse Research 
    Collapse Research Activities and Funding
    Novel regulatory events that control expression of the UGT1A1 gene
    NIH/NIGMS R01GM126074Jan 15, 2018 - Nov 30, 2021
    Role: Principal Investigator
    Neonatal hyperbilirubinemia in a humanized UGT1 animal model
    NIH/NIGMS R01GM100481Mar 15, 2012 - Dec 31, 2015
    Role: Principal Investigator
    Co-repressors SMRT and NCoR1 regulate UGT1A1 gene expression
    NIH/NIGMS R01GM086713Sep 1, 2009 - Apr 30, 2018
    Role: Principal Investigator
    NIH/NIEHS P42ES010337Jul 1, 2000 - Mar 31, 2022
    Role: Principal Investigator
    NIH/NCI R01CA079834Dec 17, 1998 - Nov 30, 2002
    Role: Principal Investigator
    Regulated Properties of the Human UGT1A1 Gene.
    NIH/NIGMS R01GM049135Apr 1, 1994 - Nov 30, 2007
    Role: Principal Investigator
    NIH/NIGMS R01GM036590Apr 1, 1986 - Jun 30, 2001
    Role: Principal Investigator
    NIH/NCI R01CA037139Apr 1, 1984 - Jun 30, 1996
    Role: Principal Investigator
    Specialized Cancer Center Support Grant
    NIH/NCI P30CA023100Apr 1, 1978 - Apr 30, 2019
    Role: Co-Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Chen S, Tukey RH. Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos. 2018 11; 46(11):1745-1755. PMID: 30093417.
      View in: PubMed
    2. Fujiwara R, Yoda E, Tukey RH. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet. 2018 Feb; 33(1):9-16. PMID: 29079228.
      View in: PubMed
    3. Fujiwara R, Mitsugi R, Uemura A, Itoh T, Tukey RH. Severe Neonatal Hyperbilirubinemia in Crigler-Najjar Syndrome Model Mice Can Be Reversed With Zinc Protoporphyrin. Hepatol Commun. 2017 Oct; 1(8):792-802. PMID: 29399656.
      View in: PubMed
    4. Lu W, Rettenmeier E, Paszek M, Yueh MF, Tukey RH, Trottier J, Barbier O, Chen S. Crypt Organoid Culture as an in Vitro Model in Drug Metabolism and Cytotoxicity Studies. Drug Metab Dispos. 2017 07; 45(7):748-754. PMID: 28468837.
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    5. Yoda E, Paszek M, Konopnicki C, Fujiwara R, Chen S, Tukey RH. Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress. Sci Rep. 2017 Apr 19; 7:46489. PMID: 28422158.
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    6. Yueh MF, Chen S, Nguyen N, Tukey RH. Developmental, Genetic, Dietary, and Xenobiotic Influences on Neonatal Hyperbilirubinemia. Mol Pharmacol. 2017 May; 91(5):545-553. PMID: 28283555.
      View in: PubMed
    7. Chen S, Lu W, Yueh MF, Rettenmeier E, Liu M, Paszek M, Auwerx J, Yu RT, Evans RM, Wang K, Karin M, Tukey RH. Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A. 2017 02 21; 114(8):E1432-E1440. PMID: 28167773.
      View in: PubMed
    8. Hirashima R, Itoh T, Tukey RH, Fujiwara R. Prediction of drug-induced liver injury using keratinocytes. J Appl Toxicol. 2017 07; 37(7):863-872. PMID: 28138970.
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    9. Hinds TD, Hosick PA, Chen S, Tukey RH, Hankins MW, Nestor-Kalinoski A, Stec DE. Mice with hyperbilirubinemia due to Gilbert's syndrome polymorphism are resistant to hepatic steatosis by decreased serine 73 phosphorylation of PPARa. Am J Physiol Endocrinol Metab. 2017 04 01; 312(4):E244-E252. PMID: 28096081.
      View in: PubMed
    10. Hirashima R, Michimae H, Takemoto H, Sasaki A, Kobayashi Y, Itoh T, Tukey RH, Fujiwara R. Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity. Mol Pharmacol. 2016 09; 90(3):265-74. PMID: 27413119; PMCID: PMC4998668 [Available on 09/01/17].
    11. Liu M, Chen S, Yueh MF, Fujiwara R, Konopnicki C, Hao H, Tukey RH. Cadmium and arsenic override NF-?B developmental regulation of the intestinal UGT1A1 gene and control of hyperbilirubinemia. Biochem Pharmacol. 2016 06 15; 110-111:37-46. PMID: 27060662; PMCID: PMC5010383 [Available on 06/15/17].
    12. Touboul T, Chen S, To CC, Mora-Castilla S, Sabatini K, Tukey RH, Laurent LC. Stage-specific regulation of the WNT/ß-catenin pathway enhances differentiation of hESCs into hepatocytes. J Hepatol. 2016 06; 64(6):1315-26. PMID: 26921690.
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    13. Mitsugi R, Sumida K, Fujie Y, Tukey RH, Itoh T, Fujiwara R. Acyl-glucuronide as a Possible Cause of Trovafloxacin-Induced Liver Toxicity: Induction of Chemokine (C-X-C Motif) Ligand 2 by Trovafloxacin Acyl-glucuronide. Biol Pharm Bull. 2016; 39(10):1604-1610. PMID: 27725437.
      View in: PubMed
    14. Yueh MF, Tukey RH. Triclosan: A Widespread Environmental Toxicant with Many Biological Effects. Annu Rev Pharmacol Toxicol. 2016; 56:251-72. PMID: 26738475; PMCID: PMC4774862 [Available on 01/06/17].
    15. Barateiro A, Chen S, Yueh MF, Fernandes A, Domingues HS, Relvas J, Barbier O, Nguyen N, Tukey RH, Brites D. Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia. Mol Pharmacol. 2016 Jan; 89(1):84-93. PMID: 26480925; PMCID: PMC4702100 [Available on 01/01/17].
    16. Liu M, Chen S, Yueh MF, Wang G, Hao H, Tukey RH. Reduction of p53 by knockdown of the UGT1 locus in colon epithelial cells causes an increase in tumorigenesis. Cell Mol Gastroenterol Hepatol. 2016 Jan; 2(1):63-76.e5. PMID: 26807433.
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    17. Fujiwara R, Maruo Y, Chen S, Tukey RH. Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia. Toxicol Appl Pharmacol. 2015 Nov 15; 289(1):124-32. PMID: 26342858; PMCID: PMC4708261 [Available on 11/15/16].
    18. Landrigan PJ, Wright RO, Cordero JF, Eaton DL, Goldstein BD, Hennig B, Maier RM, Ozonoff DM, Smith MT, Tukey RH. The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health. Environ Health Perspect. 2015 Oct; 123(10):909-18. PMID: 25978799; PMCID: PMC4590764.
    19. Kutsuno Y, Hirashima R, Sakamoto M, Ushikubo H, Michimae H, Itoh T, Tukey RH, Fujiwara R. Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity toward Endogenous Substances in Humanized UGT1 Mouse Brain. Drug Metab Dispos. 2015 Jul; 43(7):1071-6. PMID: 25953521; PMCID: PMC4468441.
    20. Sakamoto M, Itoh T, Tukey RH, Fujiwara R. Nicotine regulates the expression of UDP-glucuronosyltransferase (UGT) in humanized UGT1 mouse brain. Drug Metab Pharmacokinet. 2015 Aug; 30(4):269-75. PMID: 26210671; PMCID: PMC4752199.
    21. Yueh MF, Taniguchi K, Chen S, Evans RM, Hammock BD, Karin M, Tukey RH. The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proc Natl Acad Sci U S A. 2014 Dec 02; 111(48):17200-5. PMID: 25404284; PMCID: PMC4260592.
    22. Aoshima N, Fujie Y, Itoh T, Tukey RH, Fujiwara R. Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia. Sci Rep. 2014 Sep 11; 4:6343. PMID: 25209391; PMCID: PMC4160704.
    23. Kutsuno Y, Itoh T, Tukey RH, Fujiwara R. Glucuronidation of drugs and drug-induced toxicity in humanized UDP-glucuronosyltransferase 1 mice. Drug Metab Dispos. 2014 Jul; 42(7):1146-52. PMID: 24764149; PMCID: PMC4053997.
    24. Maruo Y, Morioka Y, Fujito H, Nakahara S, Yanagi T, Matsui K, Mori A, Sato H, Tukey RH, Takeuchi Y. Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice. J Pediatr. 2014 Jul; 165(1):36-41.e1. PMID: 24650397; PMCID: PMC4123958.
    25. Yueh MF, Chen S, Nguyen N, Tukey RH. Developmental onset of bilirubin-induced neurotoxicity involves Toll-like receptor 2-dependent signaling in humanized UDP-glucuronosyltransferase1 mice. J Biol Chem. 2014 Feb 21; 289(8):4699-709. PMID: 24403077; PMCID: PMC3931032.
    26. Chen S, Yueh MF, Bigo C, Barbier O, Wang K, Karin M, Nguyen N, Tukey RH. Intestinal glucuronidation protects against chemotherapy-induced toxicity by irinotecan (CPT-11). Proc Natl Acad Sci U S A. 2013 Nov 19; 110(47):19143-8. PMID: 24191041; PMCID: PMC3839688.
    27. Shibuya A, Itoh T, Tukey RH, Fujiwara R. Impact of fatty acids on human UDP-glucuronosyltransferase 1A1 activity and its expression in neonatal hyperbilirubinemia. Sci Rep. 2013 Oct 09; 3:2903. PMID: 24104695; PMCID: PMC3793218.
    28. Kutsuno Y, Sumida K, Itoh T, Tukey RH, Fujiwara R. Glucuronidation of drugs in humanized UDP-glucuronosyltransferase 1 mice: Similarity with glucuronidation in human liver microsomes. Pharmacol Res Perspect. 2013 Oct; 1(1):e00002. PMID: 25505556; PMCID: PMC4184567.
    29. Sumida K, Kawana M, Kouno E, Itoh T, Takano S, Narawa T, Tukey RH, Fujiwara R. Importance of UDP-glucuronosyltransferase 1A1 expression in skin and its induction by UVB in neonatal hyperbilirubinemia. Mol Pharmacol. 2013 Nov; 84(5):679-86. PMID: 23950218; PMCID: PMC3807078.
    30. Konopnicki CM, Dickmann LJ, Tracy JM, Tukey RH, Wienkers LC, Foti RS. Evaluation of UGT protein interactions in human hepatocytes: effect of siRNA down regulation of UGT1A9 and UGT2B7 on propofol glucuronidation in human hepatocytes. Arch Biochem Biophys. 2013 Jul 15; 535(2):143-9. PMID: 23562620; PMCID: PMC4059507.
    31. Li T, Yu RT, Atkins AR, Downes M, Tukey RH, Evans RM. Targeting the pregnane X receptor in liver injury. Expert Opin Ther Targets. 2012 Nov; 16(11):1075-83. PMID: 22913318; PMCID: PMC4319648.
    32. Yueh MF, Li T, Evans RM, Hammock B, Tukey RH. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha. PLoS One. 2012; 7(6):e37705. PMID: 22761658; PMCID: PMC3376094.
    33. Chen S, Yueh MF, Evans RM, Tukey RH. Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice. Hepatology. 2012 Aug; 56(2):658-67. PMID: 22371261; PMCID: PMC3383890.
    34. Fujiwara R, Chen S, Karin M, Tukey RH. Reduced expression of UGT1A1 in intestines of humanized UGT1 mice via inactivation of NF-?B leads to hyperbilirubinemia. Gastroenterology. 2012 Jan; 142(1):109-118.e2. PMID: 21983082; PMCID: PMC3428231.
    35. Vogel A, Ockenga J, Tukey RH, Manns MP, Strassburg CP. Genotyping of the UDP-glucuronosyltransferase (UGT) 1A7 gene revisited. Gastroenterology. 2011 May; 140(5):1692-3. PMID: 21440586.
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    36. Fujiwara R, Nguyen N, Chen S, Tukey RH. Developmental hyperbilirubinemia and CNS toxicity in mice humanized with the UDP glucuronosyltransferase 1 (UGT1) locus. Proc Natl Acad Sci U S A. 2010 Mar 16; 107(11):5024-9. PMID: 20194756; PMCID: PMC2841904.
    37. Cai H, Nguyen N, Peterkin V, Yang YS, Hotz K, La Placa DB, Chen S, Tukey RH, Stevens JC. A humanized UGT1 mouse model expressing the UGT1A1*28 allele for assessing drug clearance by UGT1A1-dependent glucuronidation. Drug Metab Dispos. 2010 May; 38(5):879-86. PMID: 20124398; PMCID: PMC2872941.
    38. Savas U, Machemer DE, Hsu MH, Gaynor P, Lasker JM, Tukey RH, Johnson EF. Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J Biol Chem. 2009 Jun 12; 284(24):16541-52. PMID: 19366684; PMCID: PMC2713544.
    39. Chouinard S, Yueh MF, Tukey RH, Giton F, Fiet J, Pelletier G, Barbier O, Bélanger A. Inactivation by UDP-glucuronosyltransferase enzymes: the end of androgen signaling. J Steroid Biochem Mol Biol. 2008 Apr; 109(3-5):247-53. PMID: 18467088.
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    40. Nguyen N, Bonzo JA, Chen S, Chouinard S, Kelner MJ, Hardiman G, Bélanger A, Tukey RH. Disruption of the ugt1 locus in mice resembles human Crigler-Najjar type I disease. J Biol Chem. 2008 Mar 21; 283(12):7901-11. PMID: 18180294.
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    41. Bonzo JA, Bélanger A, Tukey RH. The role of chrysin and the ah receptor in induction of the human UGT1A1 gene in vitro and in transgenic UGT1 mice. Hepatology. 2007 Feb; 45(2):349-60. PMID: 17256720.
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    42. Yueh MF, Tukey RH. Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice. J Biol Chem. 2007 Mar 23; 282(12):8749-58. PMID: 17259171.
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    43. Pezzoli K, Tukey R, Sarabia H, Zaslavsky I, Miranda ML, Suk WA, Lin A, Ellisman M. The NIEHS Environmental Health Sciences Data Resource Portal: placing advanced technologies in service to vulnerable communities. Environ Health Perspect. 2007 Apr; 115(4):564-71. PMID: 17450225; PMCID: PMC1852670.
    44. Operaña TN, Tukey RH. Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation. J Biol Chem. 2007 Feb 16; 282(7):4821-9. PMID: 17179145.
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    45. Senekeo-Effenberger K, Chen S, Brace-Sinnokrak E, Bonzo JA, Yueh MF, Argikar U, Kaeding J, Trottier J, Remmel RP, Ritter JK, Barbier O, Tukey RH. Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor alpha activation. Drug Metab Dispos. 2007 Mar; 35(3):419-27. PMID: 17151188.
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    46. Operaña TN, Nguyen N, Chen S, Beaton D, Tukey RH. Human CYP1A1GFP expression in transgenic mice serves as a biomarker for environmental toxicant exposure. Toxicol Sci. 2007 Jan; 95(1):98-107. PMID: 17065433.
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    47. Verreault M, Senekeo-Effenberger K, Trottier J, Bonzo JA, Bélanger J, Kaeding J, Staels B, Caron P, Tukey RH, Barbier O. The liver X-receptor alpha controls hepatic expression of the human bile acid-glucuronidating UGT1A3 enzyme in human cells and transgenic mice. Hepatology. 2006 Aug; 44(2):368-78. PMID: 16871576.
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    48. Chen S, Beaton D, Nguyen N, Senekeo-Effenberger K, Brace-Sinnokrak E, Argikar U, Remmel RP, Trottier J, Barbier O, Ritter JK, Tukey RH. Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem. 2005 Nov 11; 280(45):37547-57. PMID: 16155002.
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    49. Machemer DE, Tukey RH. The role of protein kinase C in regulation of TCDD-mediated CYP1A1 gene expression. Toxicol Sci. 2005 Sep; 87(1):27-37. PMID: 15947024.
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    50. Bonzo JA, Chen S, Galijatovic A, Tukey RH. Arsenite inhibition of CYP1A1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin is independent of cell cycle arrest. Mol Pharmacol. 2005 Apr; 67(4):1247-56. PMID: 15630080.
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    51. Yueh MF, Bonzo JA, Tukey RH. The role of Ah receptor in induction of human UDP-glucuronosyltransferase 1A1. Methods Enzymol. 2005; 400:75-91. PMID: 16399344.
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    52. Chen S, Operaña T, Bonzo J, Nguyen N, Tukey RH. ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem. 2005 Feb 11; 280(6):4350-9. PMID: 15572374.
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    53. Galijatovic A, Beaton D, Nguyen N, Chen S, Bonzo J, Johnson R, Maeda S, Karin M, Guengerich FP, Tukey RH. The human CYP1A1 gene is regulated in a developmental and tissue-specific fashion in transgenic mice. J Biol Chem. 2004 Jun 04; 279(23):23969-76. PMID: 15037607.
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    54. Xie W, Yeuh MF, Radominska-Pandya A, Saini SP, Negishi Y, Bottroff BS, Cabrera GY, Tukey RH, Evans RM. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci U S A. 2003 Apr 01; 100(7):4150-5. PMID: 12644700; PMCID: PMC153063.
    55. Chen S, Nguyen N, Tamura K, Karin M, Tukey RH. The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosis. J Biol Chem. 2003 May 23; 278(21):19526-33. PMID: 12637498.
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    56. Yueh MF, Huang YH, Hiller A, Chen S, Nguyen N, Tukey RH. Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1. J Biol Chem. 2003 Apr 25; 278(17):15001-6. PMID: 12566446.
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    57. Tukey RH, Strassburg CP, Mackenzie PI. Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol. 2002 Sep; 62(3):446-50. PMID: 12181419.
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    58. Huang YH, Galijatovic A, Nguyen N, Geske D, Beaton D, Green J, Green M, Peters WH, Tukey RH. Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3. Pharmacogenetics. 2002 Jun; 12(4):287-97. PMID: 12042666.
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    59. Strassburg A, Strassburg CP, Manns MP, Tukey RH. Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. Mol Pharmacol. 2002 Feb; 61(2):320-5. PMID: 11809856.
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    60. Tukey RH, Strassburg CP. Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol Pharmacol. 2001 Mar; 59(3):405-14. PMID: 11179432.
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    61. Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol. 2000; 40:581-616. PMID: 10836148.
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