George Burslem, PhD

Many cancers result from a genetic mutation causing an “always on” protein. Current treatments are based on the de-activation of the proteins by blocking that protein’s active site. Herein I propose an alternative approach in which proteins are permanently degraded rather than temporarily deactivated, which may prove to be a more favourable form of therapy. To do this, I will take advantage of the cell’s own natural ability to degrade proteins when they are in excess or no longer needed. I will design and prepare compounds which recruit the native protein degradation machinery to the target proteins by creating a bridge between protein degradation components and the target protein. We propose to prepare compounds capable of the degradation of target proteins involved in leukemia. Specifically, we focus on PRMT1, which is a protein important in acute myeloid leukemia (AML), especially in children. We will assess these compounds for the ability to degrade target proteins in cell-based models. It is conceivable that by employing protein degradation, it may be possible to completely remove all disease-causing protein and restore cancerous cells to their normal pathway. The ultimate goal is to produce a drug that may be useful for the treatment of AML while simultaneously increasing our understanding of what causes cancer.