Cancer and inflammation in the gastrointestinal tract
My laboratory studies cancer and inflammation in the gastrointestinal tract by integrating genetically engineered mouse models with biochemistry and structural biology, proteomics and genomics, and bioinformatics and systems biology. Our primary cancer research goal over the past decade has been to understand the biology of the RAS family oncogenes at a level that will allow us to design and implement precision medicine approaches for RAS-mutant colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). Our work has helped to refine the fundamental principles of precision medicine, in particular by demonstrating that closely related cancer genes, and allelic forms of the same gene, can be functionally distinct and therefore require distinct therapeutic interventions. Through our work, my laboratory has strongly integrated into the HMS and Broad Institute cancer research community. Our ongoing work focuses on the application of mass spectrometry to mouse models of K-RAS driven cancer, the identification of synthetic lethal partners with mutant forms of K-RAS, understanding allele-specific functions of K-RAS across gastrointestinal cancers, and the development of computational models of K-RAS signaling and genetics.
Our work on inflammation addresses two complementary and intertwined goals: (1) to understand inflammatory signaling at the level of protein networks and (2) to bring the concept of personalized medicine to the field of inflammatory bowel disease (IBD) research. Much of our early work in this domain was devoted to the development of methods to apply computational modeling approaches to signaling data from mouse models of inflammatory signaling driven by tumor necrosis factor alpha. In addition to studying general mechanisms of homeostasis, we have sought to characterize protein signaling mechanisms that drive chronic inflammation.