Named Grant:

The Omer Ashkenazi Memorial Project Grant

About the Investigator:

Dr. Shifman designs and engineers new proteins that bind to established cancer targets and disrupt abnormal processes in cancer, paving the way for the development of new therapeutic molecules. Dr. Shifman received her PhD from the University of Pennsylvania and conducted her postdoctoral training at the California Institute of Technology. She is presently an Associate Professor and Chair of the Department of Biological Chemistry at the Hebrew University of Jerusalem.

About the Research:

Mutations in the RAS protein are found in 30% of all human cancers, including 98% of pancreatic cancers, 52% of colorectal cancers, and 32% of lung cancers. Despite the established role of mutant RAS in cancer progression, efforts to design drugs that target this protein have been largely unsuccessful. Very recently, a drug that targets RAS carrying one particular mutation has been approved by the FDA, demonstrating the therapeutic potential of targeting RAS. This first success emphasizes the urgent need to search for new therapies that act against additional RAS mutants.

Dr. Shifman and her team propose to target RAS by engineering a human protein, Nore1A, that is known to inhibit pro-cancer activities and also exhibits additional anticancer activity of its own. In this project, they will design a variant of the Nore1A protein that is able to act specifically against a specific mutant derivative of RAS (RAS G12D) that frequently occurs in cancer. They will address the challenge of delivering this therapeutic protein into the tumor environment by supplying it with the ability to penetrate inside cancer cells, where mutated RAS is located. This work should contribute to our understating of RAS-driven cancers and facilitate development of new and much-needed therapeutics.