Pediatric Pharmacology Research Unit

Daniel W. Nebert, MS, MD

Appointment

Professor

Email

dan.nebert@uc.edu

Phone

513-558-4347

Fax

513-558-3562

Bio

International leader in elucidation of:

the diversity, specificity, functions, evolution and nomenclature of several drug-metabolizing enzyme gene superfamilies and their role in metabolism of endogenous substrates as well as of foreign chemicals;
mechanisms by which pharmacogenetics and pharmacogenomics determine susceptibility to toxicity, teratogenicity and carcinogenicity by environmental agents including pharmaceuticals.
Gene-drug interactions; gene-environment interactions.

Credentials

MS and MD: Oregon Health Sciences University, Portland, Ore., 1964

Residency: Pediatrics, UCLA, Los Angeles

Board-qualified: Pediatrics, 1968

Board-qualified: Human genetics, 1985

Research

Genetics, molecular pharmacology, toxicology, teratogenesis, carcinogenesis, signal transduction pathways, evolution, genomics, gene & allele nomenclature.

Publications, Most Recent

Nebert DW, Sophos NA, Vasiliou V, Nelson DR. (2004) Cyclophilin nomenclature problems, or, 'a visit from the sequence police'.Hum Genomics 1:381-8.
Nebert DW. (2004) Conflicts of interests: declarations for all.Environ Health Perspect 112:A980.
Nebert DW. The scientific career of Daniel W Nebert.Proceedings of the 15th International Symposium on Microsomes and Drug Oxidations (Oesch F, ed) Medimond S.R.L. Publishers, Bologna, Italy, 2004; pp 25-32
Kleiner HE, Vulimiri SV, Hatten WB, Reed MJ, Nebert DW, Jefcoate CR, DiGiovanni J. (2004) Role of cytochrome p4501 family members in the metabolic activation of polycyclic aromatic hydrocarbons in mouse epidermis.Chem Res Toxicol 17:1667-74.
Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW. (2004) Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.Pharmacogenetics 14:1-18.
Nelson DR, Nebert DW. (2004) The truth about mouse, human, worms and yeast.Hum Genomics 1:146-9.
Nebert DW, Dalton TP, Okey AB, Gonzalez FJ. (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer.J Biol Chem 279:23847-50.
Toraason M, Albertini R, Bayard S, Bigbee W, Blair A, Boffetta P, Bonassi S, Chanock S, Christiani D, Eastmond D, Hanash S, Henry C, Kadlubar F, Mirer F, Nebert D, Rapport S, Rest K, Rothman N, Ruder A, Savage R, Schulte P, Siemiatycki J, Shields P, Smith M, Tolbert P, Vermeulen R, Vineis P, Wacholder S, Ward E, Waters M, Weston A. (2004) Applying new biotechnologies to the study of occupational cancer--a workshop summary.Environ Health Perspect 112:413-6.
Wu C, Nebert DW. (2004) Update on genome completion and annotations: Protein Information Resource.Hum Genomics 1:229-33.
Shertzer HG, Clay CD, Genter MB, Schneider SN, Nebert DW, Dalton TP. (2004) Cyp1a2 protects against reactive oxygen production in mouse liver microsomes.Free Radic Biol Med 36:605-17.
Shertzer HG, Clay CD, Genter MB, Chames MC, Schneider SN, Oakley GG, Nebert DW, Dalton TP. (2004) Uncoupling-mediated generation of reactive oxygen by halogenated aromatic hydrocarbons in mouse liver microsomes.Free Radic Biol Med 36:618-31.
Uno S, Dalton TP, Derkenne S, Curran CP, Miller ML, Shertzer HG, Nebert DW. (2004) Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation.Mol Pharmacol 65:1225-37.
Uno S, Dalton TP, Sinclair PR, Gorman N, Wang B, Smith AG, Miller ML, Shertzer HG, Nebert DW. (2004) Cyp1a1(-/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria.Toxicol Appl Pharmacol 196:410-21.
Zhang K, Zhang S, Zheng K, Hou Y, Liao L, He Y, Zhang L, Nebert DW, Shi J, Su Z, Xiao C. (2004) Novel P143L polymorphism of the LCAT gene is associated with dyslipidemia in Chinese patients who have coronary atherosclerotic heart disease.Biochem Biophys Res Commun 318:4-10.
Nebert DW, Vasiliou V. (2004) Analysis of the glutathione S-transferase (GST) gene family.Hum Genomics 1:460-4.
Dalton TP, Chen Y, Schneider SN, Nebert DW, Shertzer HG. (2004) Genetically altered mice to evaluate glutathione homeostasis in health and disease.Free Radic Biol Med 37:1511-26.
Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT. (2004) Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family.J Lipid Res 45:1958-61.
Nebert DW, Vesell ES. (2004) Advances in pharmacogenomics and individualized drug therapy: exciting challenges that lie ahead.Eur J Pharmacol 500:267-80.
Nebert DW. (2005) Role of host susceptibility to toxicity and cancer caused by pesticides: cytochromes P450.J Biochem Mol Toxicol 19:184-6.
Jiang Z, Dalton TP, Jin L, Wang B, Tsuneoka Y, Shertzer HG, Deka R, Nebert DW. (2005) Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus.Hum Mutat 25:196-206.
Derkenne S, Curran CP, Shertzer HG, Dalton TP, Dragin N, Nebert DW. (2005) Theophylline pharmacokinetics: comparison of Cyp1a1(-/-) and Cyp1a2(-/-) knockout mice, humanized hCYP1A1_1A2 knock-in mice lacking either the mouse Cyp1a1 or Cyp1a2 gene, and Cyp1(+/+) wild-type mice.Pharmacogenet Genomics 15:503-11.
Shen D, Dalton TP, Nebert DW, Shertzer HG. (2005) Glutathione redox state regulates mitochondrial reactive oxygen production.J Biol Chem 280:25305-12.
Dalton TP, He L, Wang B, Miller ML, Jin L, Stringer KF, Chang X, Baxter CS, Nebert DW. (2005) Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis.Proc Natl Acad Sci U S A 102:3401-6.
Liu H, Zhang S, Lin J, Li H, Huang A, Xiao C, Li X, Su Z, Wang C, Nebert DW, Zhou B, Zheng K, Shi J, Li G, Huang D. (2005) Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese.Metabolism 54:568-72.
Greaves P, Clothier B, Davies R, Higginson FM, Edwards RE, Dalton TP, Nebert DW, Smith AG. (2005) Uroporphyria and hepatic carcinogenesis induced by polychlorinated biphenyls-iron interaction: absence in the Cyp1a2(-/-) knockout mouse.Biochem Biophys Res Commun 331:147-52.
Mackenzie PI, Walter Bock K, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, Nebert DW. (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily.Pharmacogenet Genomics 15:677-85.
Chen Y, Shertzer HG, Schneider SN, Nebert DW, Dalton TP. (2005) Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels.J Biol Chem 280:33766-74.
Cheung C, Ma X, Krausz KW, Kimura S, Feigenbaum L, Dalton TP, Nebert DW, Idle JR, Gonzalez FJ. (2005) Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice humanized for CYP1A1 and CYP1A2.Chem Res Toxicol 18:1471-8.
Nebert DW. (2005) Inter-individual susceptibility to environmental toxicants-A current assessment.Toxicol Appl Pharmacol 207:34-42.
Uno S, Dalton TP, Dragin N, Curran CP, Derkenne S, Miller ML, Shertzer HG, Gonzalez FJ, Nebert DW. (2006) Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate.Mol Pharmacol 69:1103-14.
Genter MB, Clay CD, Dalton TP, Dong H, Nebert DW, Shertzer HG. (2006) Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment.Biochem Biophys Res Commun 342:1375-81.
Curran CP, Miller KA, Dalton TP, Vorhees CV, Miller ML, Shertzer HG, Nebert DW. (2006) Genetic differences in lethality of newborn mice treated in utero with coplanar versus non-coplanar hexabromobiphenyl.Toxicol Sci 89:454-64.
Li Y, Zhang D, Jin W, Shao C, Yan P, Xu C, Sheng H, Liu Y, Yu J, Xie Y, Zhao Y, Lu D, Nebert DW, Harrison DC, Huang W, Jin L. (2006) Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.J Clin Invest 116:506-11.
Nebert DW. (2006) Comparison of gene expression in cell culture to that in the intact animal: relevance to drugs and environmental toxicants. Focus on "development of a transactivator in hepatoma cells that allows expression of phase I, phase II, and chemical defense genes".Am J Physiol Cell Physiol 290:C37-41.
He L, Girijashanker K, Dalton TP, Reed J, Li H, Soleimani M, Nebert DW. (2006) ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family: characterization of transporter properties.Mol Pharmacol 70:171-80.
Dragin N, Dalton TP, Miller ML, Shertzer HG, Nebert DW. (2006) For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential.J Biol Chem 281:18591-600.
Genter MB, Marlowe J, Kevin Kerzee J, Dragin N, Puga A, Dalton TP, Nebert DW. (2006) Naphthalene toxicity in mice and aryl hydrocarbon receptor-mediated CYPs.Biochem Biophys Res Commun.
Zhang G, Nebert DW, Chakraborty R, Jin L. (2006) Statistical power of association using the extreme discordant phenotype design.Pharmacogenet Genomics 16:401-413.
Vasiliou V, Ross D, Nebert DW. (2006) Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family.Hum Genomics 2:329-35.
Vasiliou V, Ross D, Nebert DW. (2006) Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family.Hum Genomics 2:329-35.
Jiang Z, Dragin N, Jorge-Nebert LF, Martin MV, Guengerich FP, Aklillu E, Ingelman-Sundberg M, Hammons GJ, Lyn-Cook BD, Kadlubar FF, Saldana SN, Sorter M, Vinks AA, Nassr N, von Richter O, Jin L, Nebert DW. (2006) Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype.Pharmacogenet Genomics 16:359-67.

Editorial Boards
Biochemical Pharmacology, since 1972
DNA and Cell Biology, since 1986 (Associate Editor, Section on Molecular Pharmacology, since 1987)
Endocrinology, since 1989
Pharmacogenetics, since 1991
Environmental Health Perspectives, since 1997
European Journal of Pharmacology, since 2002
Human Genomics, since 2002

Presentations
At least 15 since January, 1999.