The work in our laboratory can roughly be divided into two areas: cancer biology and systems biology.
Our cancer biology work focuses largely on the influence of activating Ras mutations in the pathogenesis of colorectal cancer. Our primary approach is to genetically manipulate Ras signaling pathways both in vivo (in the mouse colonic epithelium) and in vitro (in human colorectal cancer cells). We have recently developed mouse models of colon cancer that rely on mutationally activated K-Ras or N-Ras. Tumors from these mice mimic human colon cancers at both the molecular and histologic levels.
Our lab also applies systems biology approaches in an effort to understand genetically complex diseases. This work focuses on the development of computational models of dysregulated signaling networks in the context of disease. Currently, we are focusing on two classes of disease: 1) chronic inflammatory conditions of the gastrointestinal tract (i.e., inflammatory bowel diseases); and 2) neurodegenerative diseases (e.g., Alzheimer’s disease and frontotemporal dementia).