Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Cancer remains one of the leading causes of death in Canada. While new treatment approaches, such as immunotherapy, have improved prognoses for many patients, these therapies still fail in many cases. A key reason for this is that cancer cells have evolved ways to 'hide' from the immune system. One emerging mechanism of immune evasion involves changes to the sugars, termed glycans, that coat the surface of every human cell. In healthy cells, these sugars play essential roles in communication between cells. However, cancer cells alter their sugar patterns in a way that makes them appear normal to the immune system, thereby allowing tumours to evade detection and destruction by the immune system. Treatments that target this sugar alterations are now in clinical alterations, but we still do not understand what causes these sugar changes in the first place. My project aims to address this by asking the following question: which cancer genetic mutations allow cancer cells to rewire their sugar coating to evade the immune system? Using cutting-edge CRISPR base editing technology, I will systematically introduce thousands of commonly observed cancer mutations into healthy breast cells, one-by-one. I will then measure how each mutation changes the sugar coating on cells. This will generate a comprehensive 'map' of the mutations that drive glycome changes in cancer. I will then further test how these mutations alter communications between cancer cells and immune cells, and whether they make cancer cells more resistant to being destroyed by the immune system. This project will uncover new genetic biomarkers that may help clinicians predict which patients will benefit from glycan-targeted immunotherapies. It may also reveal new drug treatments that may serve as next-generation of glyco-immunotherapy. Through bridging cancer genetics with glycobiology, my project has the potential to advance precision medicine and improve cancer care across Canada.