Orphan nuclear receptors (those that lack a well defined physiologic ligand) control nearly every major physiologic and biochemical process in eukaryotes - cell metabolism (e.g., cholesterol, energy, bile acids), xenobiotic detoxification, cell differentiation (e.g., gastrulation, retinal development), circadian rhythm, and cancer cell growth and apoptosis (e.g., NURR77). Alterations in the receptor are directly linked to human disease (e.g., NOR1 and extraskeletal myxoid chondrosarcomas).
Of these receptors, the pregnane X receptor (PXR) [or steroid and xenobiotic receptor (SXR)] is a key regulator of genes encoding drug metabolizing and transport proteins. In addition, PXR has been implicated in cancer drug resistance, carcinogenesis and pathophysiologic states like osteomalacia. Our laboratory focuses on defining the role of PXR and other orphans in: (i) xenobiotic metabolism and pharmacology and (ii) carcinogenesis, organogenesis, anticancer drug resistance and inflammation. We hope that with a fundamental understanding of the role of PXR in the above processes, we will be able to develop smart molecular approaches towards controlling aberrant drug pharmacology and tumor cell growth.