The Sheltzer Lab at Yale University is seeking postdoctoral researchers for a funded project researching and developing anti-cancer therapeutic strategies.

Our laboratory is developing and applying cutting-edge genetic techniques 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 act via mechanisms that are independent of their reported target(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 CDK11 – the first inhibitor of this kinase to be discovered. 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:

• Bhattacharjee, D., Bakar, J., Sausville, E.L., Mendelson, B.E., Long, K., Smith, J.C., Sheltzer, J.M. (2022). A drug’s most potent target is not necessarily the source of its anti-cancer activity. bioRxiv. doi.org/10.1101/2022.10.16.512438.
• 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 experimental design 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 .

A PhD in Molecular Biology, Genetics, Biochemistry, Pharmacology, or another related discipline.

Candidates who are interested in applying to this position should send a CV and cover letter to Dr. Sheltzer at Jason.Sheltzer@yale.edu .