Postdoctoral Research Associate - Chemical Biology & Therapeutics

A postdoc position is available in the lab of Dr. Taosheng Chen

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 molecular basis of signal crosstalk among nuclear receptors, and (3) 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 and investigate biological mechanisms. 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.

Position Responsibilities:

The postdoctoral fellows will work in a multidisciplinary team to study the regulation of PXR and CAR, or CYP3A4 and CYP3A5, by developing or characterizing novel chemical probes (i.e., small molecule inhibitors or degraders). The fellows will contribute to or lead the effort of the multidisciplinary team (of biologists, medicinal chemists and structural biologists), organize and prepare manuscripts for publications. The fellows will be trained on manuscript and grant writing and encouraged (but not required) to prepare and submit grant proposals.

Minimum Education and/or Training:

Individuals with a strong publication record and are motivated to perform high quality research and publish impactful papers are encouraged to apply. Candidates must have (or soon receive) a PhD degree in biology, chemical biology, or structural biology.

Special Skills, Knowledge, and Abilities:

Required skills:

• For a PhD in Biology/chemical biology: cell & molecular biology, biochemistry, or chemical biology

• For a PhD in Structural Biology: protein expression and purification, X-ray crystallography, in silico modeling of protein-ligand interactions

Preferred skills: experience in using chemical biology approaches to investigate protein-ligand interactions and understand the mechanistic insights and functional outcomes.

Soft skills: effective communications skills; ability to work independently and collaboratively; willing to and capable of learning new skills needed to complete the research projects.

About the lab and St. Jude:

Upon completion of the training, the trainees are expected to become independent researchers or leaders in either academic or industrial settings. The Chen Lab provides a unique training environment: in addition to basic mechanistic chemical biology research, the postdoctoral fellow will learn and gain experience in small molecule drug discovery from target validation, chemical probe discovery to preclinical mechanistic studies; collaborate with senior staff members from diverse background (biologists, structural biologists and medicinal chemists). Former Chen Lab postdocs have landed jobs as Assistant Professors in Universities, Senior Scientists in Pharmaceutical Companies, or Staff Scientists at St. Jude.

St. Jude Children’s Research Hospital is a world-class research institution dedicated to pediatric cancer and other catastrophic diseases of childhood. The first and only National Cancer Institute (NCI)-designated Comprehensive Cancer Center devoted solely to children. Our 300 faculty work across the spectrum of basic, translational, clinical, and population science in a highly collaborative multidisciplinary environment that includes a Nobel laureate and members of the National Academy of Science and the National Academy of Medicine. St. Jude is ranked on Fortune Magazine’s “Best Workplaces in Health Care & Biopharma” and Glassdoor’s “Best Places to Work,” and is located in the heart of Memphis, Tennessee, a vibrant an