Superfund Research Program

David J. Waxman

Boston University
5 Cummington Street
Boston, Massachusetts 02215
Phone: 617-353-7401
Fax: 617-353-7404
Email: djw@bu.edu

Projects

• Boston University: Activation Of Orphan Receptors By Chlorinated Hydrocarbons (1995 - 2000)
• Boston University: Nuclear Receptors and Gonadal Toxicity of Xenochemicals (2005-2012)
• Boston University: PPAR, Hormones, and Xenobiotics (2000 - 2005)

Research Briefs

• 39 - Tracking Down the Mechanisms of Trichloroethylene-Induced Toxicity

Publications

2011

• Bagchi G, Stanley KA, Zhang Y, Waxman DJ. 2011. Complex modulation of androgen responsive gene expression by methoxyacetic acid. Reprod Biol Endocrinol 9:doi:10.1186/1477-7827-9-42 PMID:21453523 PMCID:PMC3083340

2010

• Arany I, Baliga R, Tian N, Waxman DJ. 2010. Cytochrome-P450 2B1 gene silencing attenuates puromycin aminonucleoside-induced cytotoxicity in glomerular epithelial cells. Kidney International 78:182-190. doi:10.1038/ki.2010.100 PMID:20407477 PMCID:PMC3053138
• Bagchi G, Zhang Y, Waxman DJ. 2010. Impact of methoxyacetic acid on mouse Leydig cell gene expression. Reprod Biol Endocrinol 8:65. doi:10.1186/1477-7827-8-65 PMID:20565877 PMCID:PMC2909983
• Ling G, Sugathan A, Mazor T, Fraenkel E, Waxman DJ. 2010. Unbiased, genome-wide in vivo mapping of transcriptional regulatory elements reveals sex differences in chromatin structure associated with sex-specific liver gene expression. Mol Cell Biol 30(23):5531-5544. doi:10.1128/MCB.00601-10 PMID:20876297 PMCID:PMC2976433
• Liu H, Tian N, Arany I, Bigler S, Waxman DJ, Shah S, Baliga R. 2010. Cytochrome P450 2B1 mediates complement-dependent sublytic injury in a model of membranous nephropathy. J Biol Chem 285:40901-10. doi:10.1074/jbc.M110.165498 PMID:20947506 PMCID:PMC3003390
• Wauthier V, Sugathan A, Meyer RD, Dombkowski AA, Waxman DJ. 2010. Intrinsic Sex Differences in the Early Growth Hormone Responsiveness of Sex-Specific Genes in Mouse Liver. Mol Endocrinol 24(3):667-668. doi:10.1210/me.2009-0454 PMID:20150183 PMCID:PMC2840812

2009

• Bagchi G, Hurst CH, Waxman DJ. 2009. Interactions of methoxyacetic acid with androgen receptor. Toxicol Appl Pharmacol 238(2):101-110. doi:10.1016/j.taap.2008.03.015 PMID:18486176 PMCID:PMC2742301

2008

• Bagchi G, Waxman DJ. 2008. Toxicity of ethylene glycol monomethyl ether: impact on testicular gene expression. Int J Androl 31(2):269-274. doi:10.1111/j.1365-2605.2007.00846.x PMID:18179559 PMCID:PMC3286123
• Holloway MG, Miles GD, Dombkowski AA, Waxman DJ. 2008. Liver-Specific Hepatocyte Nuclear Factor-4α Deficiency: Greater Impact on Gene Expression in Male than in Female Mouse Liver. Mol Endocrinol 22(5):1274-1286. doi:10.1210/me.2007-0564 PMID:18276827 PMCID:PMC2366185
• Johnston TP, Waxman DJ. 2008. Circulating free fatty acids are increased independently of PPARgamma activity after administration of poloxamer 407 to mice. Can J Physiol Pharmacol 86(9):643-649. doi:10.1139/y08-070 PMID:18758514 PMCID:PMC2615679
• Johnston TP, Waxman DJ. 2008. Peroxisome proiiferator-actlvated receptor (PPAR) agonists: using a mouse model of atherogenic dyslipidemia to better understand the PPAR-LXR-ABCA1 signaling pathway for accelerating cholesterol elimination. In: 22nd Ann Mtg Amer Assoc Pharm Sci.
• Johnston TP, Waxman DJ. 2008. The induction of atherogenic dyslipidaemia in poloxamer 407-treated mice is not mediated through PPARalpha. J Pharm Pharmacol 60(6):753-759. doi:10.1211/jpp.60.6.0011 PMID:18498712 PMCID:PMC2496925
• Waxman DJ, Chang TK. 2008. Nuclear receptor regulation of hepatic cytochrome P450 enzymes. In: Encyclopedia of Molecular Pharmacology (2nd ed.). Springer, pp.889-893.

2007

• Clodfelter KH, Miles GD, Wauthier V, Holloway MG, Zhang X, Hodor P, Ray WJ, Waxman DJ. 2007. Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysis. Physiol Genomics 31:63-74. PMID:17536022
• Ma X, Idle JR, Malfatti MA, Krausz KW, Nebert DW, Chen C, Felton JS, Waxman DJ, Gonzalez FJ. 2007. Mouse lung CYP1A1 catalyzes the metabolic activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis 28(3):732-737. doi:10.1093/carcin/bgl184 PMID:17052995 PMCID:PMC1829392
• Sun L, Chen C, Waxman DJ, Liu H, Halpert JR, Kumar S. 2007. Re-engineering cytochrome P450 2B11dH for enhanced metabolism of several substrates including the anti-cancer prodrugs cyclophosphamide and ifosfamide. Arch Biochem Biophys 458(2):167-174. doi:10.1016/j.abb.2006.12.021 PMID:17254539 PMCID:PMC1805465

2006

• Chang TK, Crespi CL, Waxman DJ. 2006. Spectrophotometric analysis of human CYP2E1-catalyzed p-nitrophenol hydroxylation. Methods Mol Biol 320:127-131. doi:10.1385/1-59259-998-2:127 PMID:14577224
• Chang TK, Crespi CL, Waxman DJ. 2006. Spectrophotometric analysis of human CYP2E1-catalyzed p-nitrophenol hydroxylation. In: Methods in Molecular Biology, Vol 320. Humana Press, Inc, Louisville, KY. pp.127-131.
• Chang TK, Waxman DJ. 2006. Catalytic assays for human cytochrome P450. In: Methods in Molecular Biology, Vol 320. Humana Press, Inc, Louisville, KY. pp.73-83.
• Chang TK, Waxman DJ. 2006. Enzymatic analysis of cDNA-expressed human CYP1A1, CYP1A2 and CYP1B1 with 7-ethoxyresorufin as substrate. In: Methods in Molecular Biology, Vol 320. Humana Press, Inc, Louisville, KY. pp.85-90.
• Chang TK, Waxman DJ. 2006. Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). J Mol Biol 38(1-2):51-73. PMID:16684648
• Clodfelter KH, Holloway MG, Hodor P, Park S, Ray WJ, Waxman DJ. 2006. Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis. Mol Endocrinol 20(6):1333-1351. doi:10.1210/me.2005-0489 PMID:16469768
• Clodfelter KH, Waxman DJ, Vajda S. 2006. Computational solvent mapping reveals the importance of local conformational changes for broad substrate specificity in mammalian cytochromes P450. Biochemistry 45(31):9393-407. PMID:16878974
• Crespi CL, Chang TK, Waxman DJ. 2006. CYP2D6-dependent bufuralol 1'-hydroxylation assayed by reversed-phase ion-pair high performance liquid chromatography with fluorescence detection. In: Methods in Molecular Biology, Vol 320. Humana Press, Inc, Louisville, KY. pp.121-125.
• Kaya T, Mohr SC, Waxman DJ, Vajda S. 2006. Computational screening of phthalate monoesters for binding to PPARgamma. Chem Res Toxicol 19(8):999-1009. doi:10.1021/tx050301s PMID:16918238
• Shipley JM, Waxman DJ. 2006. Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methycholanthrene. Toxicol Appl Pharmacol 213(2):87-97. PMID:16257430
• Waxman DJ, Chang TK. 2006. Use of 7-ethoxycoumarin to monitor multiple enzymes in the human CYP1, CYP2 and CYP3 families. In: Methods in Molecular Biology, Vol 320. Humana Press, Inc, Louisville, KY. pp.153-156.
• Waxman DJ, Chang TK. 2006. Use of 7-ethoxycoumarin to monitor multiple enzymes in the human CYP1, CYP2, and CYP3 families. Methods Mol Biol 320:153-156. doi:10.1385/1-59259-998-2:153 PMID:14577228

2005

• Chang TK, Waxman DJ. 2005. Pregnane X receptor-mediated transcription. Methods Enzymol 400:588-598. doi:10.1016/S0076-6879(05)00033-9 PMID:16399372
• Hurst CH, Waxman DJ. 2005. Interactions of endocrine-active environmental chemicals with the nuclear receptor PXR. Toxicol Sci 87:299-311.
• Kumar S, Chen C, Waxman DJ, Halpert JR. 2005. Directed evolution of mammalian cytochrome P450 2B1: mutations outside of the active site enhance the metabolism of several substrates, including the anticancer prodrugs cyclophosphamide and ifosfamide. J Biol Chem 280(20):19569-19575. doi:10.1074/jbc.M500158200 PMID:15774478
• Sheu S, Kaya T, Waxman DJ, Vajda S. 2005. Exploring the binding site structure of the PPAR gamma ligand-binding domain by computational solvent mapping. Biochemistry 44(4):1193-1209. doi:10.1021/bi048032c PMID:15667213

2004

• Ahluwalia A, Clodfelter KH, Waxman DJ. 2004. Sexual dimorphism of rat liver gene expression: Regulatory role of growth hormone revealed by deoxyribonucleic acid microarray analysis. Mol Endocrinol 18(3):747-760. PMID:14684848
• Clodfelter KH, Waxman DJ. 2004. Computational solvent mapping reveals major differences in substrate binding between bacterial and mammalian cytochrome. In: Proceedings of the New England Member Enzyme Conference.
• Hurst CH, Waxman DJ. 2004. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription. Toxicol Appl Pharmacol 199(3):266-274. PMID:15364542
• Schlezinger JJ, Howard G, Hurst CH, Emberley JK, Waxman DJ, Webster TF, Sherr DH. 2004. Environmental and endogenous peroxisome proliferator-activated receptor gamma agonists induce bone marrow B cell growth arrest and apoptosis: Interactions between mono(2-ethylhexyl)phthalate, 9-cis-retinoic acid, and 15-Deoxy-Delta(12,14)-prostaglandin J(2). J Immunol 173(5):3165-3177. PMID:15322177
• Shipley JM, Waxman DJ. 2004. Simultaneous, bidirectional inhibitory crosstalk between PPAR and STAT5b. Toxicol Appl Pharmacol 199(3):275-284. PMID:15364543
• Su T, Waxman DJ. 2004. Impact of dimethyl sulfoxide on expression of nuclear receptors and drug-inducible cytochromes P450 in primary rat hepatocytes. Arch Biochem Biophys 424(2):226-234. doi:10.1016/j.abb.2004.02.008 PMID:15047195

2003

• Hurst CH, Waxman DJ. 2003. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci 74(2):297-308. doi:10.1093/toxsci/kfg145 PMID:12805656
• Shipley JM, Waxman DJ. 2003. Down-regulation of STAT5b transcriptional activity by ligand-activated peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma. Mol Pharmacol 64(2):355-364. PMID:12869640
• Su T, Waxman DJ. 2003. Impact of dimethyl sulphoxide on expression of nuclear receptors and drug-inducible cytochromes P450 (CYPs) in primary rat hepatocytes. FASEB J 17(4):A240-A240Part1Suppl..
• Waxman DJ. 2003. Nuclear receptor regulation of drug-metzbolizing P450 enzymes. In: Encyclopedia Reference of Molecular Pharmacology. Springer-Verlag Press,

2002

• Ahluwalia A, Waxman DJ. 2002. Global gene expression profiling in rat liver using oligonucleotide microarrays: evaluation of the regulatory role of hormones and xenobiotics. In: New England Drug Metabolism Discussion Group Summer Symposium. Worcester, MA.
• Goss KA, Clodfelter KH, Waxman DJ. 2002. Understanding P450 structure-function relationships using DNA shuffling mutagenesis. In: Boston University-Humboldt University Bioinformatics Workshop, Boston, MA.
• Zhou Y, Davey HW, McLachlan MJ, Xie T, Waxman DJ. 2002. Elevated basal expression of liver peroxisomal beta-oxidation enzymes and CYP4A microsomal fatty acid omega-hydroxylase in STAT5b(-/-) mice: cross-talk in vivo between peroxisome proliferator-activated receptor and signal transducer and activator of transcription signaling pathways. Toxicol Appl Pharmacol 182(1):1-10. PMID:12127257

2001

• Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM. 2001. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci U S A 98(6):3375-3380. PMID:11248086

2000

• Waxman DJ. 2000. Receptor-mediated signaling events in cytochrome P450 gene regulation. In: Proceedings of the Early Toxicity Screening in Drug Discovery Conference.

1999

• Maloney EK, Waxman DJ. 1999. trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicol Appl Pharmacol 161(2):209-218. PMID:10581215
• Waxman DJ. 1999. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR and PPAR. Arch Biochem Biophys 369(1):11-23. PMID:10462436
• Zhou Y, Waxman DJ. 1999. Inhibitory cross-talk between JAK2/STAT5b and PPARa. In: Proceedings of the 81st Annual Endocrine Society Meeting. pp.108.
• Zhou Y, Waxman DJ. 1999. STAT5b down-regulates peroxisome proliferator-activated receptor alpha transcription by inhibition of ligand-independent activation function region-1 trans-activation domain. J Biol Chem 274(42):29874-29882. PMID:10514468

1998

• Chang TK, Waxman DJ. 1998. Catalytic assays for human cytochrome P450. Methods Mol Biol 107:95-102. PMID:14577216
• Chang TK, Waxman DJ. 1998. Enzymatic analysis of cDNA-expressed human CYP1A1, CYP1A2, and CYP1B1 with 7-ethoxyresorufin as substrate. Methods Mol Biol 107:103-109. PMID:14577217
• Crespi CL, Chang TK, Waxman DJ. 1998. CYP2D6-dependent bufuralol 1'-hydroxylation assayed by reversed-phase ion-pair high-performance liquid chromatography with fluorescence detection. Methods Mol Biol 107:141-145. PMID:14577223
• Zhou Y, Waxman DJ. 1998. Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids. Environ Health Perspect 106Suppl.4:983-988. PMID:9703482
• Zhou Y, Waxman DJ. 1998. Cross-talk between JAK-STAT and PPARα signaling pathways: Growth hormone (GH) inhibition of PPARα activity mediated by STAT5b. In: Proceedings of the 12th International Symposium on Microsomes and Drug Oxidations. pp.123.

1997

• Chang TK, Crespi CL, Waxman DJ. 1997. Spectrophotometric Analysis of Human CY P2El -Catalyzed pNitrophenol Hydroxylation. Chapter 17 in: Methods in Molecular Biology series: Cytochrome P450 Protocols. Humana Press, Inc., pp.147-152.
• Crespi CL, Chang TK, Waxman DJ. 1997. CYP2D6-dependent bufuralol 1'-hydroxylation assayed by reversed-phase ion-pair high performance liquid chromatography with fluorescence detection. Chapter 16 in: Methods in Molecular Biology series: Cytochrome P450 Protocols. Humana Press, Inc., pp.141-146.
• Waxman DJ, Chang TK. 1997. Use of 7-Ethoxycoumarin to Monitor Multiple Enzymes in the Human CYPI, CYP2, and CYP3 Families. Chapter 21 in: Methods in Molecular Biology series: Cytochrome P450 Protocols. Humana Press, Inc., pp.175-180.
• Zhou Y, Waxman DJ. 1997. Cross-talk between PPAR and JAK-STAT signaling pathways regulating liver P450 expression. In: Proceedings of the 15th New England Membrane Enzyme Conference.

1996

• Peters JM, Zhou Y, Ram PA, Lee SS, Gonzalez FJ, Waxman DJ. 1996. Peroxisome proliferator-activated receptor a required for gene induction by dehydroepiandrosterone 3b-sulfate. Mol Pharmacol 50(1):67-74.
• Waxman DJ. 1996. Role of metabolism in the activation of dehydroepiandrosterone as a peroxisome proliferator. Journal of Endocrinology 150:S129-S147. PMID:8943797
• Zhou Y, Peters JM, Ram PA, Lee SS, Gonzalez FJ, Waxman DJ. 1996. Peroxisome proliferator-activated receptor a (PPARa) mediates gene induction by dehydroepiandrosterone 3b-sulfate (DHEA-S). In: Proceedings of the 11th International Symposium on Microsomes and Drug Oxidations. pp.209.

1995

• Waxman DJ. 1995. Metabolism of DHEA and related steroids: interaction with liver cytochromes P450 (CYPs). In: Proceedings of the International Symposium on DHEA (Dehydroepiandrosterone) Transformation. pp.29.