Adult gastrointestinal stem cells are the targets of carcinogenic gene mutations and are believed to be the cells of origin of luminal gastrointestinal cancers. Simon's team's published work has examined the clonality and genetic mutation burden of pre-neoplastic gastrointestinal disease. Their current research focuses on the homeostatic cell-signaling pathways that control intestinal stem cells and the dysregulation of these pathways in carcinogenesis. The wnt pathway is the best characterised system and promotes the maintenance and proliferation of stem cells, however other signaling pathways such as the Bone Morphogenetic Protein (BMP) and Notch pathway cross-talk and interact with wnt signaling. Recent work from their laboratory on hereditary polyposis syndromes and genome-wide association studies in sporadic colorectal cancer patients has implicated the BMP pathway’s involvement in predisposition to colorectal cancer.