The Sheltzer Lab at Yale University is seeking postdoctoral researchers for a funded project identifying novel cancer drug targets.
Our laboratory is using CRISPR mutagenesis to uncover unique cancer “dependencies” and to characterize the mechanism-of-action of different anti-cancer agents. Unexpectedly, we have found that many drugs used in human patients have been designed to target proteins that are non-essential for cancer proliferation. Moreover, we’ve demonstrated that these drugs necessarily act by inhibiting some other off-target protein(s).
We are applying a combination of techniques, including CRISPR screens, targeted mutagenesis, live-cell microscopy, and molecular pharmacology, to study a variety of cancer drugs and to figure out how they actually work. Through these approaches, we have found that one mis-characterized drug functions by targeting the cyclin-dependent kinase CDK11B – the first inhibitor of this kinase to be discovered. This finding sheds light on a poorly-studied cell cycle regulator and unlocks an entirely new target for cancer drug development. We are seeking to both learn more CDK11B’s function in cancer and to apply similar approaches to characterize other small molecule drugs. By discovering the true mechanism-of-action of mis-characterized inhibitors, we hope to identify biomarkers that can be used to accurately predict patient sensitivity and to monitor drug efficacy in vivo. More information can be found in our publications, including:
Lin A., and Sheltzer J.M. (2020). Discovering and validating cancer genetic dependencies: approaches and pitfalls. Nature Reviews Genetics. doi:10.1038/s41576-020-0247-7.
Lin, A., Giuliano, C.J., Palladino, A., John, K.M., Abramowicz, C., Yuan, M.L., Sausville, E.L., Lukow, D.A., Luwei, L., Chait, A.R., Galluzzo., Z.C., Tucker, C., Sheltzer, J.M. (2019). Off-target toxicity is a common mechanism-of-action of cancer drugs undergoing clinical trials. Science Translational Medicine. 11, eaaw8412.
The Sheltzer Lab is a highly-collaborative environment that values rigorous research and that welcomes scientists from all backgrounds. We are located at Yale University, an internationally-renowned research university located in the historic city of New Haven, Connecticut. Yale has long been recognized as an outstanding environment for nurturing young scientists, with postdoctoral researchers being an integral part of the discovery process.
Additional information on research in the Sheltzer Lab can be found on our website: www.sheltzerlab.org. Candidates who are interested in applying to this position should send a CV and cover letter to Dr. Sheltzer at Jason.Sheltzer@yale.edu.
Yale University is an EO/AA Employer. All qualified applicants will receive consideration for employment and will not be discriminated against on the basis of race, color, religion, sex, sexual orientation, gender identity, national origin, age, disability or protected veteran status.
Tagged as: Life Sciences
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