Dr. Westcott is developing improved in vivo models for studying the complex interactions between colorectal cancer and the immune system. The powerful genome editing technology CRISPR-Cas9 will be leveraged to rapidly generate a suite of novel mouse models of colorectal cancer harboring distinct mutational signatures seen in human cancer. He will use genome-wide sequencing and preclinical studies to dissect the role of these mutational signatures in promoting cancer cell detection by the immune system, and in modulating response to immunotherapies. These studies will provide new tools to probe fundamental questions of tumor immunology, with the ultimate goal of improving the poor response of colorectal cancers to immunotherapies.