Abstract

Our laboratory is centered in understanding the structure and function of ATP dependent chromatin remodeling complexes, with an emphasis on their role in human cancer. Over the past several years, we have developed extensive expertise in the application of protein biochemistry, structural analyses, and genomics to uncover the mechanistic sequelae of perturbation to the genes encoding subunits of the mammalian SWI /SNF (BAF) ATP -dependent chromatin remodeling complex. The growing number of exome and genome-wide sequencing studies in human cancers has revealed a significant and previously unappreciated role for BAF complexes as both tumor suppressors and oncogenes. Specific genes encoding the subunits of these complexes are mutated in highly specialized cancer subtypes; our group integrates human cancer genetics with biochemistry, structural biology, chemical biology, and functional genomics and epigenomics to understand BAF complex function and to inform new strategies toward therapeutic development. In particular, we have focused our efforts on cancers with well-defined genomic lesions, such as synovial sarcoma, malignant rhabdoid tumor, and more recently, a range of human tumors that exhibit unique dependency on specific BAF complex subunits and transcription factors which tether to their surfaces.