Two postdoctoral positions are available at the Genomic Stability and Metabolism Group (PI: Urbain Weyemi, Ph.D.) within the Developmental Therapeutics Branch, CCR, NCI in Bethesda, Maryland. Our group aims to understand the dialogue between genomic instability and metabolism in human diseases, particularly in cancer and neurodegeneration. We apply multiple genomics and metabolomics tools to assess how changes in genome repair pathways affect metabolic abilities of cancer cells. Our goal is to understand how cancer cells undergo metabolic reprogramming to escape therapeutic agents targeting DNA repair.
The research projects
Ataxia-telangiectasia mutated (ATM) kinase controls DNA damage responses upon DNA double-strand break (DSB) formation (Bonner et al., 2008), and loss of ATM kinase activity or heterozygosity for pathogenic ATM gene variants increases cancer risks (Swift et al.,1991). Indeed, ATM is frequently mutated across cancer types (Choi et al., 2016). Conversely, ATM genetic deficiency or inhibition can be harnessed to sensitize cancer cells to radiotherapy (Durant et al., 2018). Using metabolism-centered CRISPR screens, we recently demonstrated that Kelch-like ECH-associated protein 1 (KEAP1) acts as a key factor involved in desensitizing cancer cells to ATM inhibition both in vitro and in vivo. Cells depleted of KEAP1 exhibited an aberrant overexpression of the cystine transporter SLC7A11, robustly relied on cysteine metabolism and underwent cell death, presumably because of disulfide stress induced ATM inhibition (https://www.biorxiv.org/content/10.1101/2022.05.03.490553v1.full).
In the current project, we will explore the relationship between ATM and other essential metabolic hits from our CRISPR screen. The successful applicants will utilize molecular biology and biochemical tools to study how ATM and other DNA repair proteins control metabolic pathways in cancer cells. Postdoctoral fellows in our group are encouraged to explore new ideas.
Training opportunities are augmented by collaborations with colleagues, physicians and pharmacologists from the intramural and extramural communities. Fellows are encouraged to take advantage of formal, focused courses (e.g., training in bioinformatics and translational research), actively engage in mentoring and participate in a variety of community activities including the NIH’s DNA Repair Interest Group and the NCI's Center of Excellence in Chromosome Biology.
Qualifications and Job Details
Required and Preferred Skills
A Ph.D. or M.D. degree that includes training in molecular biology and biochemistry.
Training in bioinformatics will be considered a plus. Some experience with animal studies will be greatly valued.
About the NCI Center for Cancer Research
The Center for Cancer Research (CCR) is home to nearly 250 basic and clinical research groups located on two campuses just outside of Washington, D.C. CCR is part of the National Cancer Institute (NCI) and makes up the largest component of the research effort at the National Institutes of Health (NIH). Centrally supported by long-term funding and a culture of complete intellectual freedom, CCR scientists are able to pursue the most important and challenging problems in cancer research. We collaborate with academic and commercial partners and advocacy groups across the world in efforts to prevent, diagnose and treat cancer and HIV/AIDS. The CCR research portfolio covers the full spectrum of biological and biomedical research. Our work ranges from basic to translational and clinical, and our clinical trials are conducted in the NIH Clinical Center, the world’s largest hospital dedicated to clinical research that offers a robust infrastructure to support CCR’s patients on an estimated 250 open studies. The success of CCR is grounded in an exceptionally strong discovery research program that provides the foundation for the seamless translation of insights from bench to bedside. Read more about CCR, the benefits of working at CCR and hear from our staff on their CCR experiences.
Bethesda is one of the most highly educated communities in the United States and has a nationally renowned school system. The city is a thriving suburban center close to Washington, D.C., and home to many restaurants, retailers and a flourishing arts and entertainment district.