Paul E. Thomas, Ph.D.
EOHSI Bldg. Office Room 428
170 Frelinghuysen Road
Department of Environmental & Occupational Medicine
UMDNJ-Robert Wood Johnson Medical School
Piscataway, NJ 08854
EOHSI Bldg. Lab Room 427
Dr Thomas’ research interests include breast cancer cause and prevention and the possible role of cytochromes P450 in the activation/inactivation of endogenous hormones. Additionally, his research seeks to understand whether environmental chemicals that act as estrogens (known as endocrine disruptors) are in part responsible for the disproportionally high incidence of breast cancer in industrialized countries. Cytochrome P450 is a super family of enzymes responsible for both oxidations of estrogens as well as drugs and xenobiotics to facilitate their elimination from the body as well as their metabolism to reactive metabolites that can bind to macromolecules leading to toxicity or initiation of carcinogenesis in the cell as well as oxidative stress. He is an internationally-recognized expert in developing antibodies that distinguish among individual enzymes of this super family. Dr. Thomas has produced over 100 different monoclonal and polyclonal antibodies that recognize rat and human cytochromes P450 and have been widely used to study the regulation, organ distribution, intracellular localization and function of these enzymes. Many of the epitopes recognized by these antibodies have been mapped in an effort to develop more specific antibodies and to develop those which inhibit catalysis.
--Bisphenol A is an environmental contaminant that has weak estrogenic activity but is considered by many to be an endocrine disruptor to which humans are widely exposed. We have found that this chemical is metabolized by rats to 4 distinct reactive metabolites that can be trapped as glutathione derivatives. We are exploring whether this metabolism could be a route to detrimental effects on the organism apart from endocrine effects.
-- We have found that dansylglutathione is a substrate for microsomal-glutathione transferase despite earlier reports that it wasn’t. This has important implications for in vitro measurements of reactive electrophilic intermediates formed by oxidative enzymes in different tissues.
-- When implanted with slow release estradiol the female ACI rat has been shown to mimic human breast cancer better than any other rodent model. In a collaborative study with Dr. Nanjoo Suh’s laboratory we have found that a diet enriched in gamma-tocopherols inhibits mammary tumor proliferation and decreases serum inflammatory markers.
Course co-coordinator for Biochemical Toxicology, a 2nd year graduate course in the Joint Graduate Program in Toxicology. Course coordinator for Pharmaceutical Microbiology which is a 4th year required course for a Pharm. D. degree in the Ernest Mario School of Pharmacy ofRutgersUniversity.
Ad hoc reviewer for Drug Metabolism and Disposition, Drug Metabolism Reviews, Cancer Research, Archives of Biochemistry Biophysics, Biochemical Pharmacology.
Charter member of the International Society for the Study of Xenobiotics and Member of the following professional Societies: American Association for Cancer Research, American Chemical Society, American Society for Pharmacology and Experimental Therapeutics, American Society of Biochemistry & Molecular Biology, and the Society of Toxicology. Consultant on cytochrome P450 for Sanofi-Aventis.
Hong M, Li S, Zhou F, Thomas PE, You G. Putative transmembrane domain 12 of the human organic anion transporter hOAT1 determines transporter stability and maturation efficiency. J Pharmacol Exp Ther. 2010 Feb;332(2):650-8. [PMID: 19892921]
Lee HJ, Paul S, Atalla N, Thomas PE, Lin X, Yang I, Buckley B, Lu G, Zheng X, Lou YR, Conney AH, Maehr H, Adorini L, Uskokovic M, Suh N. Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity. Cancer Prev Res (Phila). 2008 Nov;1(6):476-84. [PMID: 19138995]
Zhu LR, Thomas PE, Lu G, Reuhl KR, Yang GY, Wang LD, Wang SL, Yang CS, He XY, Hong JY. CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical study with a new peptide-specific antibody. Drug Metab Dispos. 2006 Oct;34(10):1672-6. [PMID: 16815959]
Gu X, Ke S, Liu D, Sheng T, Thomas PE,RabsonAB, Gallo MA, Xie W, Tian Y. Role of NF-kappaB in regulation of PXR-mediated gene expression: a mechanism for the suppression of cytochrome P-450 3A4 by proinflammatory agents. J Biol Chem. 2006 Jun 30;281(26):17882-9. Epub 2006 Apr 10. [PMID: 16608838]
Jan YH, Mishin V, Busch CM, Thomas PE. Generation of specific antibodies and their use to characterize sex differences in four rat P450 3A enzymes following vehicle and pregnenolone 16alpha-carbonitrile treatment. Arch Biochem Biophys. 2006 Feb 15;446(2):101-10. [PMID: 16448623]
Mishin VM, Thomas PE. Characterization of hydroxyl radical formation by microsomal enzymes using a water-soluble trap, terephthalate. Biochem Pharmacol. 2004 Aug 15;68(4):747-52. [PMID: 15276082]
Turan VK, Sanchez RI, Li JJ, Li SA, Reuhl KR, Thomas PE, Conney AH, Gallo MA, Kauffman FC, Mesia-Vela S. The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17beta-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16alpha-hydroxyestradiol, and 4-hydroxyestrone. J Endocrinol. 2004 Oct;183(1):91-9. [PMID: 15525577]
Dvorzhinski D, Thalasila A, Thomas PE, Nelson D, Li H, White E, Dipaola RS. A novel proteomic coculture model of prostate cancer cell growth. Proteomics. 2004 Oct;4(10):3268-75. [PMID: 15378687]
Dean B, Chang S,DossGA, King C, Thomas PE..Glucuronidation, oxidative metabolism, and bioactivation of enterolactone in rhesus monkeys. Arch Biochem Biophys. 2004 Sep 15;429(2):244-51. [PMID: 15313229]