Grant: CIHR Fellowship

Chromatin biology and epigenetics represents an important emerging area in cancer science with the potential to reveal novel approaches to cancer treatment. Chromatin regulators (CRs) add, erase or interpret modifications of proteins called histones that help control whether a given gene is turned on or off. Consequently they are responsible for giving each cell type its specialized functions, as for example distinguishing a skin cell from a nerve cell. Many cancers have mutations of CRs, which result in abnormal, rapid growth and the loss of the specialized functions of the tissue from which the cancer is derived. Our preliminary studies indicate that mutations in CRs can also result in different sensitivity to drugs as compared to normal pancreatic cells. The goal of our proposal is to better understand how mutations in CRs "reprogram" pancreatic cancer cells by comprehensively characterizing their chromatin and histone modifications. We will then examine how blocking or inhibiting specific CRs or their target genes alter cancer cell behavior, with the goal to understand the underlying functions and mechanisms. These studies will help us understand how CR mutations increase "fitness" of the cancer cell, and how they might be exploited with new therapeutic strategies.