Julia Shifman, PhD
Project Title
Targeting Ras oncogenic mutants with AI-generated protein inhibitors
About the Investigator
Dr. Shifman is a world expert in protein design and engineering. Using a combination of computational and experimental techniques, her lab designs new proteins that bind to established cancer targets and disrupt abnormal processes in cancer, paving way to development of new therapeutic molecules. Dr. Shifman received her Ph. D. at the University of Pennsylvania and her postdoctoral training at the California Institute of Technology. She is presently an Associate Professor at the Department of Biological Chemistry at the Hebrew University of Jerusalem.
About the Research
Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), is one of the deadliest cancers, with less than 15% of patients surviving five years after diagnosis. A major reason for this poor outcome is a mutation in a gene called KRAS, which drives cancer growth and is present in most PDAC cases. For many years, KRAS was considered “undruggable” because its structure makes it difficult for conventional drugs to bind effectively.
Recently, a few small-molecule drugs have shown that KRAS can be targeted, but they work only for specific mutations, often lose effectiveness over time, and can trigger resistance. Our project aims to develop a new type of treatment that overcomes these limitations by using small proteins specifically designed to target the mutant forms of KRAS found in pancreatic cancer. Using advanced artificial intelligence tools, we will design diverse mini-proteins that attach to KRAS in unique ways, potentially stopping it from promoting cancer growth. Unlike traditional drugs that bind in a single cavity, these proteins can interact with larger areas of KRAS, which may make it harder for the cancer to become resistant. We will test these proteins in pancreatic cancer models to see if they block KRAS activity, stop cancer cells from growing, and trigger processes that lead to cancer cell death or growth arrest. This research could uncover new ways to target KRAS, provide a platform for designing next-generation cancer therapies, and ultimately improve treatment options for patients with PDAC and other cancers driven by KRAS mutations.
