Postdoctoral Research Associate - Chemical Biology & Therapuetics
About The Position
A postdoc position is available in the lab of Taosheng Chen. The Chen Lab is seeking a Postdoctoral Research Associate to work in a multidisciplinary team to study the regulation of PXR and CAR, or CYP3A4 and CYP3A5, by characterizing novel chemical probes (i.e., small molecule inhibitors or degraders) in biochemical/biophysical, cellular and animal models. Drug toxicity and resistance are the leading causes of therapeutic failures. The Chen Lab 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 form an unexpected heterodimer (Nucleic Acids Res 50:3254, 2022); revealed a mechanism that expands PXR’s ligand binding pocket to reduce ligand’s binding affinity (Proc Natl Acad Sci U S A. 120: e2217804120, 2023); and discovered the first CYP3A5-selective inhibitor and its structural basis (J Am Chem Soc 143:18467, 2021). Our goal is to understand nuclear receptor-regulated transcription networks, enzyme-drug interactions, and design therapeutic approaches to overcome drug resistance and toxicity in cellular and animal models. The postdoctoral fellows will work in a multidisciplinary team to study the regulation of PXR and CAR, or CYP3A4 and CYP3A5, by characterizing novel chemical probes (i.e., small molecule inhibitors or degraders) in biochemical/biophysical, cellular and animal models.
Requirements
- Characterize novel chemical probes (i.e., small molecule inhibitors or degraders) in biochemical/biophysical, cellular and animal models
Responsibilities
- Contribute to or lead the effort of the multidisciplinary team (of biologists, medicinal chemists and structural biologists)
- Organize and prepare manuscripts for publications
- Be trained on manuscript and grant writing
- Prepare and submit grant proposals (encouraged but not required)
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What This Job Offers
Job Type
Full-time
Career Level
Mid Level
Education Level
Ph.D. or professional degree
