Postdoctoral Fellow - Tonks Lab

Position Description
A postdoctoral position is immediately available at Cold Spring Harbor Laboratory for highly motivated Ph.D. candidates to join the Tonks Laboratory at CSHL.

Protein Tyrosine Phosphatases and the Regulation of Cell Signaling: from Basic Research to New Therapeutics
The protein phosphatases are critical, specific regulators of signaling that serve an essential function, in a coordinated manner with the protein kinases, to determine the response to a physiological stimulus. The Tonks Lab takes a multidisciplinary approach to study the structure, regulation and function of the protein tyrosine phosphatase (PTP) family of enzymes, to illustrate their fundamental importance to the control of signal transduction under normal and pathophysiological conditions. As functional studies have established links to disease, the PTPs have been garnering attention as potential therapeutic targets; however, they remain a largely untapped resource for drug development.

One focus of the lab is PTP1B, the prototypic member of the PTP family that Dr. Tonks discovered ~30 years ago. It is a validated target for diabetes and obesity, as well as HER2-positive cancer, and as such has been the subject of extensive drug discovery efforts. PTP1B is a challenging target because small molecule inhibitors that bind to the PTP active site tend to be highly charged and limited in their drug development potential; this led industry to conclude that the members of the PTP family are “undruggable”. Consequently, new approaches are required to exploit these important targets effectively and reinvigorate drug discovery efforts.

The detailed understanding of the structure and function of PTP1B, which we have generated in an academic setting, is revealing new approaches to generating small molecule drug candidates. This includes small molecules that harness the physiological regulation of PTP function by reversible oxidation, as well as allosteric inhibitors that stabilize an inactive conformation of PTP1B that is encountered in vivo in the absence of substrate. Furthermore, the Tonks Lab has identified allosteric inhibitors of PTP1B that also chelate copper specifically. These studies have opened up new and unanticipated ways to modulate the activity of critical signaling pathways in vivo. The application of these inhibitors is now revealing new functions of PTP1B and suggesting new indications in which these molecules may be applied for therapeutic benefit.

These studies serve as a template for investigation of the structure, regulation and function of members of the PTP family as a whole. Current projects are focused on defining the function of members of the PTP family in cell and animal models of disease, including cancer, metabolic disorders, inflammation, and neurodegenerative disease. In addition, there is a focus on developing drug candidate PTP inhibitors for application in such models. The Tonks lab is looking for postdoctoral fellows to work on these projects.

Position Requirements
Qualifications: Ph.D. and research experience in protein biochemistry, molecular biology and animal handling.

To apply: Interested candidates should email Dr. Tonks ([email protected]) with their CV & cover letter. In addition, please apply via the CSHL careers website at https://www.schooljobs.com/careers/cshl? Position ID 03137-R.

Environment
Cold Spring Harbor Laboratory is a world-renowned biomedical research institution in New York. It has shaped contemporary biomedical research and is the home of eight Nobel Prize laureates. Cold Spring Harbor Laboratory provides a highly dynamic and interactive research environment and also a unique opportunity of timely exposure to advances in various biomedical research fields and of interaction with a broad range of researchers from all over the world through its renowned Meetings and Courses program.

We believe that science is for everyone. We have had researchers with a variety of backgrounds and believe in the importance of diversity, equity, and inclusion.