Charles W. M. Roberts, MD
Year elected: 2010
Current membership category: Active
St. Jude Children's Research Hospital
262 Danny Thomas Place
Mail Stop 281
Memphis, TN 38105-3678
United States of America
Phone: 901-595-3913
Facsimile: 901-595-8600
Email: charles.roberts@stjude.org

Biographical statement

My laboratory is interested in the role of dysfunctional chromatin remodeling in the genesis of cancer. Epigenetic alterations likely contribute to the formation of most, if not all cancers. However, in the setting of genomic instability it is difficult to evaluate the contributions of epigenetic changes as it is unclear which are primary drivers and which arise as secondary passengers. The Swi/Snf complex, which utilizes ATP hydrolysis to remodel chromatin, is a key regulator of the epigenetic state and 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 have further shown that these lethal human cancers are diploid and indistinguishable from normal cells on SNP arrays suggesting that epigenetic alterations can serve as the central driver of oncogenic transformation. Thus, using these genomically stable cancers and our Snf5-conditional model systems, we seek to identify the fundamental mechanisms by which epigenetic alterations drive cancer formation. Given the dramatic nature in which inactivation of Snf5 leads to cancer formation, we anticipate that complete characterization of this complex will lead to insights into tumorigenesis and may further suggest novel therapeutic strategies.

Institutional affiliations

St. Jude Children's Research Hospital (Primary)

Specialties

Pediatrics