Titles and Affiliations
Director, Comprehensive Cancer Center
Research area
Investigating how mutations in a protein complex promote breast cancer.
Impact
Cancer arises when key cellular systems malfunction. One of the most common drivers of these malfunctions is disruption in a protein complex called SWI/SNF. This complex plays a central role in controlling how a broad range of genes are turned on or off. When it is not functioning properly, normal cellular processes can break down, leading to cancer. Mutations in the SWI/SNF complex are found in nearly one quarter of all cancers, making it one of the most frequently mutated cellular pathways in the disease. Despite this, little is known about how specific SWI/SNF mutations contribute to cancer formation and progression, and how to target them with therapies. Dr. Roberts aims to clarify how different SWI/SNF sub-families regulate gene expression and how their disruption drives cancer. By using diverse laboratory model systems, he is identifying unique genetic vulnerabilities in cancers with SWI/SNF mutations—vulnerabilities that do not affect healthy cells.
Progress Thus Far
Dr. Roberts and his team have already discovered several genes that, when turned off, selectively kill cancer cells with SWI/SNF mutations but leave healthy cells unharmed. The proteins encoded by these genes had not previously been linked to SWI/SNF at all, so the team has developed new laboratory tools to study where these proteins are located within the cell and how they interact with the SWI/SNF complex, along with tools that allow them to rapidly remove these proteins from cells to study their role more directly.
What’s next
In the coming year, the team will deepen its investigation into the molecular relationships between SWI/SNF and these newly discovered vulnerability genes. Key questions include: Do these proteins encoded by these genes help guide SWI/SNF to the right places in the genome? Are they required for SWI/SNF’s function? And does SWI/SNF regulate their activity? The team will study these questions both in cancer cells with SWI/SNF mutations, where these genes appear essential for survival, and in normal cells with healthy SWI/SNF function, to understand what these proteins do under typical conditions. Answering these questions will not only shed light on the fundamental biology of cancer but also pave the way for novel, precise cancer treatments tailored to tumors harboring SWI/SNF mutations.
Biography
Charles W. M. Roberts, MD, PhD, is a leader in the field of cancer epigenetics, and his research has provided new insights into the central role of chromatin remodeling perturbations in cancer, discoveries that have been translated into investigational therapies for both pediatric and adult cancer patients. His research specifically focuses on the SWI/SNF (BAF) chromatin remodeling complex. Perturbation of this complex has broad relevance to cancer as at least nine genes that encode SWI/SNF subunits are collectively mutated in over 20% of all cancers, including breast cancer. Roberts’ laboratory studies both the mechanisms by which SWI/SNF normally regulates chromatin structure and cell fate, and the mechanisms by which mutation of the complex drive cancer formation. Roberts is the director of the St. Jude Comprehensive Cancer Center and serves as an executive vice president and a full member in the Department of Oncology of St. Jude Children’s Research Hospital. Roberts received his medical and doctoral degrees from Washington University School of Medicine in St. Louis, Missouri. He completed his pediatric residency and pediatric hematology/oncology fellowship at Boston Children’s Hospital/Dana-Farber Cancer Institute. Roberts has been elected to the Society for Pediatric Research, American Society of Clinical Investigation, and American Pediatric Society.
