Curt Omiecinski, PhD

Curt Omiecinski, PhD

  • Professor Emeritus of Veterinary and Biomedical Sciences
  • Academy of Toxicological Sciences
306D Life Sciences Building
University Park, PA 16802

Areas of Expertise

  • Molecular Toxicology
  • Nuclear Receptors
  • Gene Regulation

Education

  • Postdoctoral Fellow in Molecular Toxicology, University of Vermont, Burlington, VT, 1980-83
  • PhD, Pharmacology, University of Washington, Seattle, WA, 1980
  • BS, Biology, State University of New York at Albany, 1975

Graduate Programs

  • Molecular Cellular Integrative Biosciences (MCIBS)

Research

The research in our laboratory is focused on the molecularbiology of mammalian biotransformation. Variability in the expression of biotransformation activities appears to substantially impact individual responsiveness to both pharmaceutical and toxicant exposures. One line of laboratory endeavor relates to the study of the regulatory mechanisms responsible for controlling the expression of the biotransformation enzymes. Recently, a variety of ligand-activated nuclear receptors have been characterized that serve as “xenosensors” in mammalian cells and function as transcriptional activators of a variety of genes, including the cytochrome P450s. The P450s are key components of the drug and chemical metabolism pathway. Phenobarbital (PB) is an example of clinical compound that produces marked activation of the expression of several P450 genes, in a process that is regulated by the constitutive androstane receptor (CAR). The laboratory studies signaling cascades activated by inducer exposures and nuclear events dictating altered DNA-protein and protein-protein interactions associated with the induction process. Experimental models in use include primary hepatocyte cultures and transgenic mouse systems. Investigations are underway examining the transcriptional activation processes involved in gene induction, such as the interactions of nuclear receptors with core DNA enhancer elements and the associated network of nuclear co-activator and co-repressor proteins. We are very interested in determining genetic variation in nuclear receptor structure that may impact important clinical and toxicological outcomes.

A parallel investigation in the laboratory involves the characterization of the human epoxide hydrolases, including their structure, regulation and genetic variability. These enzymes, like the P450s, also function to biotransform a variety of drug and toxic substances, typically acting upon epoxide intermediates produced by P450 reactions. Epoxide hydrolase often functions to render the epoxides less chemically reactive. Two forms of human hydrolase are being studied, the microsomal epoxide hydrolase and the soluble epoxide hydrolase. The microsomal enzyme is active against a broad array of xenobiotic chemicals whereas the soluble enzyme principally participates in the metabolism of endogenous substances such as the arachidonate derivates, the epoxyeicosotrienoic acids. Our epoxide hydrolase research program involves characterization of genetic variation, structure-function relationships, and tissue-specific regulation of their expression.

Publications

Metabolomic approaches reveal the role of CAR in energy metabolism
Journal of Proteome Research, Chen, Fengming, Coslo, Denise M., Chen, Tao, Zhang, Limin, Tian, Yuan, Smith, Philip B., Patterson, Andrew D., Omiecinski, Curtis J., 2019

Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.
Journal of proteome research, 2018

In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets
Nucleic acids research, Niu, Ben, Coslo, Denise M., Bataille, Alain R., Albert, Istvan, Pugh, Benjamin Franklin, Omiecinski, Curtis John, 2018

Activation of the Constitutive Androstane Receptor by Monophthalates
Chemical research in toxicology, Laurenzana, Elizabeth M., Coslo, Denise M., Vigilar, M. Veronica, Roman, Anthony M., Omiecinski, Curtis J., 2016

δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression
Toxicology, Takeda, Shuso, Ikeda, Eriko, Su, Shengzhong, Harada, Mari, Okazaki, Hiroyuki, Yoshioka, Yasushi, Nishimura, Hajime, Ishii, Hiroyuki, Kakizoe, Kazuhiro, Taniguchi, Aya, Tokuyasu, Miki, Himeno, Taichi, Watanabe, Kazuhito, Omiecinski, Curtis J., Aramaki, Hironori, 2014

Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture
Toxicological Sciences, Wahlang, Banrida, Cameron Falkner, K., Clair, Heather B., Al-Eryani, Laila, Prough, Russell A., Christopher States, J., Coslo, Denise M., Omiecinski, Curtis J., Cave, Matthew C., 2014

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action
Toxicology, Currie, Richard A., Peffer, Richard C., Goetz, Amber K., Omiecinski, Curtis J., Goodman, Jay I., 2014

Intronic DNA elements regulate Nrf2 chemical responsiveness of the human microsomal epoxide hydrolase gene (EPHX1) through a far upstream alternative promoter
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Su, Shengzhong, Yang, Xi, Omiecinski, Curtis J., 2014

Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter
Gene, Su, Shengzhong, Omiecinski, Curtis John, 2014

Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor
Biochemical Journal, Chen, Tao, Laurenzana, Elizabeth M., Coslo, Denise M., Chen, Fengming, Omiecinski, Curtis J., 2014

Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: A case study with phenobarbital as a model constitutive androstane receptor (CAR) activator.
Critical reviews in toxicology, Elcombe, C, Peffer, R, Wolf, D, Bailey, J, Bars, R, Bell, D, Cattley, R, Ferguson, S, Geter, D, Goetz, A, Goodman, Jovictoria, Hester, S, Jacobs, A, Omiecinski, Curtis, Schoeny, R, Xie, W, Lake, B, 2014

The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells
Developmental biology, Chen, Fengming, Zamule, Stephanie M., Coslo, Denise M., Chen, Tao, Omiecinski, Curtis John, 2013

Δ9-tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ)
Chemical research in toxicology, Takeda, Shuso, Yoshida, Kazutaka, Nishimura, Hajime, Harada, Mari, Okajima, Shunsuke, Miyoshi, Hiroko, Okamoto, Yoshiko, Amamoto, Toshiaki, Watanabe, Kazuhito, Omiecinski, Curtis J., Aramaki, Hironori, 2013

Expression of a novel mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5′-untranslated region
RNA, Nguyen, Hong Loan, Yang, Xi, Omiecinski, Curtis J., 2013

Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ9-tetrahydrocannabinol in human breast cancer cells
Journal of Toxicological Sciences, Takeda, Shuso, Harada, Mari, Su, Shengzhong, Okajima, Shunsuke, Miyoshi, Hiroko, Yoshida, Kazutaka, Nishimura, Hajime, Okamoto, Yoshiko, Amamoto, Toshiaki, Watanabe, Kazuhito, Omiecinski, Curtis John, Aramaki, Hironori, 2013

(-)-Xanthatin up-regulation of the GADD45γ tumor suppressor gene in MDA-MB-231 breast cancer cells
Toxicology, Takeda, Shuso, Noguchi, Momoko, Matsuo, Kazumasa, Yamaguchi, Yasuhiro, Kudo, Taichi, Nishimura, Hajime, Okamoto, Yoshiko, Amamoto, Toshiaki, Shindo, Mitsuru, Omiecinski, Curtis J., Aramaki, Hironori, 2013

Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration
Toxicology Letters, Takeda, Shuso, Okajima, Shunsuke, Miyoshi, Hiroko, Yoshida, Kazutaka, Okamoto, Yoshiko, Okada, Tomoko, Amamoto, Toshiaki, Watanabe, Kazuhito, Omiecinski, Curtis John, Aramaki, Hironori, 2012

The orphan nuclear receptor DAX-1 functions as a potent corepressor of the constitutive androstane receptor (NR1I3)
Molecular pharmacology, Laurenzana, Elizabeth M., Chen, Tao, Kannuswamy, Malavika, Sell, Brian E., Strom, Stephen C., Li, Yong, Omiecinski, Curtis J., 2012

Multi-species analyses of direct activators of the constitutive androstane receptor
Toxicological Sciences, Omiecinski, Curtis J., Coslo, Denise M., Chen, Tao, Laurenzana, Elizabeth M., Peffer, Richard C., 2011

Cannabidiol-2′,6′-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro
Biological and Pharmaceutical Bulletin, Takeda, Shuso, Hirayama, Akari, Urata, Shino, Mano, Nobutaka, Fukagawa, Keiko, Imamura, Midori, Irii, Ayumi, Kitajima, Satomi, Masuyama, Tomoko, Nomiyama, Mai, Tatei, Sachiko, Tomita, Saari, Kudo, Taichi, Noguchi, Momoko, Yamaguchi, Yasuhiro, Okamoto, Yoshiko, Amamoto, Toshiaki, Fukunishi, Yoshifumi, Watanabe, Kazuhito, Omiecinski, Curtis John, Aramaki, Hironori, 2011

(-)-Xanthatin selectively induces GADD45γ and stimulates caspase-independent cell death in human breast cancer MDA-MB-231 cells
Chemical research in toxicology, Takeda, Shuso, Matsuo, Kazumasa, Yaji, Kentaro, Okajima-Miyazaki, Shunsuke, Harada, Mari, Miyoshi, Hiroko, Okamoto, Yoshiko, Amamoto, Toshiaki, Shindo, Mitsuru, Omiecinski, Curtis John, Aramaki, Hironori, 2011

Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor
Toxicological Sciences, Dekeyser, Joshua G., Laurenzana, Elizabeth M., Peterson, Eric C., Chen, Tao, Omiecinski, Curtis J., 2011

Differentiation of human embryonic stem cells along a hepatic lineage
Chemico-Biological Interactions, Zamule, Stephanie M., Coslo, Denise M., Chen, Fengming, Omiecinski, Curtis John, 2011

Bioassay-directed fractionation for discovery of bioactive neutral lipids guided by relative mass defect filtering and multiplexed collision-induced dissociation
Rapid Communications in Mass Spectrometry, Stagliano, Michael, DeKeyser, Joshua, Omiecinski, Curtis, Jones, Daniel, 2010

Hepatocyte differentiation.
Methods in molecular biology (Clifton, N.J.), Olsavsky Goyak, Katy M., Laurenzana, Elizabeth M., Omiecinski, Curtis J., 2010

Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling
Toxicological Sciences, DiNatale, Brett C., Murray, Iain A., Schroeder, Jennifer C., Flaveny, Colin A., Lahoti, Tejas S., Laurenzana, Elizabeth M., Omiecinski, Curtis J., Perdew, Gary H., 2010

The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor
Biochemistry, Schroeder, Jennifer C., DiNatale, Brett C., Murray, Iain A., Flaveny, Colin A., Liu, Qiang, Laurenzana, Elizabeth M., Lin, Jyh Ming, Strom, Stephen C., Omiecinski, Curtis J., Amin, Shantu, Perdew, Gary H., 2010