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 ( ) 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:...Venture Solar is hiring a Solar Installer . As a Residential Solar Installer, you will be responsible for : Assembly, installation... ...as assigned. What youll bring: Knowledge of hand-held power tools. Experience in PV installations, roof work, general...
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