- Hematology / Oncology
- Hematology / Oncology
Washington University School of Medicine, MD/PhD, 7/88 to 6/95
St. Louis, MO
Children's Hospital Boston, 1995-1996
Boston Combined Residency Program, Children's Hospital Boston/Boston Medical Center, 1996-1997
Pediatric Hematology/Oncology Fellowship
Children's Hospital Boston/Dana-Farber Cancer Institute, 1997-2000
Pediatrics, Pediatric Hematology/Oncology
I am a physician scientist whose major focus is laboratory-based scientific investigation. I spend 75% of my time leading the endeavors of my research laboratory; 15% of my time seeing patients and supervising clinical trainees; and 10% in administrative and teaching roles collectively. The focus of my laboratory is upon understanding the role of dysfunctional chromatin remodeling and epigenetic regulation in cancer. Specifically, we study the SWI/SNF chromatin remodeling complex as genes encoding at least eight subunits of this complex are specifically mutated in 20% of all human cancers. The SWI/SNF complex was first linked to cancer when its SNF5 (INI1/SMARCB1/BAF47) subunit was found to be mutated in nearly all cases of malignant rhabdoid tumor, a highly aggressive cancer that strikes young children. Via generation of genetically engineered mouse models we demonstrated that inactivation of Snf5 leads to extremely rapid cancer formation in all mice. We have subsequently focused upon generating mechanistic understanding of how the SWI/SNF complex functions as a tumor suppressor, with a goal of leveraging this insight to pursue clinical translation not only for pediatric rhabdoid tumors but also for the wide variety of SWI/SNF mutant cancers. We have numerous publications of these efforts and have been successful in these endeavors with the opening of our first clinical trial in 2013.
During my career, I have had continuous peer-reviewed funding beginning with receipt of an NIH Medical Scientist Training Program grant, next an HHMI post-doctoral fellowship, then a KO8 award and ultimately R01 and U01 support. I was also selected as one of 13 recipients, out of 431 applicants, for an Innovative Research Grant from Stand Up to Cancer via a peer-review process conducted by a blue ribbon panel established by the AACR.
Administratively, I serve as Co-Director of the Pediatric Oncology Solid Tumor Program, where I lead our collaborative research efforts, as Co-chair the Pediatric Institutional Review Board for DF/HCC, and as leader of Departmental efforts to recruit physician scientist trainees. I am Co-Chair of the upcoming AACR meeting on Chromatin and Epigenetics in Cancer and part of the Program Committee for the 2014 AACR annual meeting. With respect to honors, I received local recognition when chosen as the 2005 recipient of the Stephen E. Sallan Leadership Award, which recognizes Pediatric Oncology staff leaders for their ability to guide, inspire and motivate others. On a national front, in 2007, I was elected to membership in the Society for Pediatric Research and in 2010 to membership in the American Society of Clinical Investigation.
Looking forward, I aim to further synthesize insights derived from my research, clinical, and administrative roles in a position of substantial leadership to pursue innovative approaches to understanding and treating pediatric cancer. My ultimate goal is to substantially improve the outcome of patients stricken with these cancers.
Chromatin Remodeling in Cancer
Role of the chromatin protein Snf5 and the SWI/SNF complex in rhabdoid and other tumors (Proc Natl Acad Sci USA 97:13796, 2000)
Development and use of a new conditional DNA inversion technique to show that Snf5 is a tumor suppressor gene whose loss of function leads rapidly to T cell lymphomas (Cancer Cell 2:415, 2002)
Demonstration that Snf5 is required for cell cycle regulation and that its inactivation cooperates with p53 loss in oncogenic transformation (Proc Natl Acad Sci USA 102:17745, 2005)
Research site for Charles M. Roberts MD, PhD