Our group studies colorectal cancer, the third most common cause of cancer deaths in the US. Colorectal cancer arises from the intestinal epithelial stem cell compartment. The stem cell compartment regulates the balance of proliferation, differentiation and cell death that maintains the epithelial layer lining the intestinal lumen. Disruption of this balance leads to colon cancer. Our research is aimed at understanding factors that cause cancer-causing disruption of the stem cell compartment.A series of studies by our group identified two genes, KCNQ1 and CFTR, as colorectal cancer tumor suppressor genes. Initially, these genes were identified as a candidate colorectal cancer driver genes in a Sleeping Beauty transposon-mediated forward genetic screen. In follow-up studies, targeted intestinal-specific deletion of Cftr and Kcnq1 in the ApcMin mouse model of intestinal tumorigenesis resulted in significantly more intestinal tumors. Most important, studies of human colon tumors demonstrated that diminished expression of either KCNQ1 or CFTR is associated with poorer prognosis.KCNQ1 and CFTR are both expressed in the intestinal epithelial stem cell compartment. They encode ion channels expressed at the cell surface. As such, they in a position to influence the cellular processes that maintain the stem cell compartment. Our current research focuses on understanding how deficiency for KCNQ1 and CFTR disrupts the stem cell compartment and promotes the development of poor prognosis colon cancer.