Postdoctoral Research Associate - Chemical Biology & Therapeutics

Postdoctoral Research Associate - Chemical Biology & Therapeutics

Location

Memphis, TN

Category

Postdoc

Department

Chemical Biology and Therapeutics

Shift

Weekday Day

Position Type

Full Time

Scheduled Weekly Hours

40

JR3417

Project

Description:

Drug toxicity and resistance are the leading causes of therapeutic failures. The Chen Lab (https://(Use the "Apply for this Job" box below).) 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: e, 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. 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.

Individuals with a strong publication record in reputable journals 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.

• For a PhD in Biology/Chemical Biology/Pharmacology: cell & molecular biology, chemical biology, or in vivo pharmacology (mouse models)
• For a PhD in Structural Biology: protein expression and purification, X‑ray crystallography, in silico modeling of protein‑ligand interactions

experience in using multidisciplinary chemical biology approaches to investigate protein‑ligand interactions and understand the mechanistic insights and in vitro/in vivo functional outcomes.

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

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 e.

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