My laboratory is interested in the role of dysfunctional chromatin remodeling in the genesis of cancer. It is increasingly clear that epigenetic modifications play a critical role in the development of cancer. The Swi/Snf complex, which utilizes ATP hydrolysis to remodel chromatin, has a potent role in the genesis of cancer. Accumulating evidence has linked the Swi/Snf complex to both human cancer and other tumor suppressor pathways indicating that the complex has diverse roles in growth regulation and tumor suppression. Indeed, we have recently demonstrated a key role for Snf5, a core member of this complex, in tumor suppression in a novel mouse model. Inactivating mutations in the SNF5 gene result in aggressive cancers in children and a familial cancer predisposition syndrome. We hypothesize that Snf5 is a master regulator of gene expression via its effects on chromatin structure and seek to identify the mechanisms by which perturbation of this ATPase chromatin remodeling complex leads to cancer formation. Given the dramatic nature in which inactivation of Snf5, leads to cancer formation, complete characterization of this complex will lead to insights into tumorigenesis and may further suggest novel therapeutic strategies. Thus, we are using mouse modeling, molecular biological, and biochemical approaches to characterize this newly appreciated mechanism of tumor suppression.