Dr. Omiecinski's research centers on the molecular genetics and regulation of human xenobiotic detoxication. The laboratory's toxicogenomic investigations seek to characterize critical determinants that specify the underlying mechanisms dictating the variable nature of interindividual responsiveness to drug and chemical exposure. One specific focus of the laboratory is the study of human microsomal epoxide hydrolase. The laboratory has characterized structural polymorphisms as well as the use of alternative gene promoter mechanisms that contribute as potential risk modifiers for chemical toxicity mediated by epoxide intermediates. Another area of focus is the biological regulation conferred by nuclear receptors, in particular the constitutive androstane receptor. Xenobiotic receptors, such as CAR and PXR, sense the cellular chemical environment and function in key regulatory circuitry that tunes the cell's genomic expression program to accommodate the specific chemical milieu. These receptor control circuits exhibit diversity within cells, tissues and among individuals, in part due to the generation of structurally distinct sets of receptors generated by alternative RNA splicing - an area of particular research focus for the laboratory.