St. Jude Children's Research Hospital
Memphis, TN, USA
Project Description: Drug toxicity and resistance are the leading causes of therapeutic failures. The Chen Lab (https://www.stjude.org/research/labs/chen-lab-taosheng.html) studies: (1) the chemical regulation of nuclear xenobiotic receptors, (2) the mechanism of selective modulation of highly homologous drug-metabolizing enzymes. We are taking a hypothesis-driven and technology-enabled multidisciplinary approach to develop chemical probes, investigate biological mechanisms, and evaluate in vivo efficacy. In particular we use the promiscuous pregnane X receptor (PXR) and constitutive androstane receptor (CAR) as models. PXR and CAR transcriptionally regulate cytochrome P450 3A4 (CYP3A4) and CYP3A5—drug-metabolizing enzymes that metabolize more than 50% of clinical drugs, the dysregulation of which contributes to drug toxicity and drug resistance. We have developed the first selective PXR antagonist (Nat Commun 8:741, 2017; Nat Commun 15:4054, 2024); established that PXR and CAR...