Harvard Catalyst Profiles

Our laboratory is interested in understanding the mechanisms by which large macromolecular machines in the nuclei of our cells known as ATP-dependent chromatin remodeling complexes govern the accessibility of our genome, and hence, gene expression. Notably, genes encoding the protein subunits of mSWI/SNF family of ATP-dependent chromatin remodelers are mutated in over 20% of human cancers, including several cancer types in which mSWI/SNF complex subunit perturbations (i.e. deletions, single amino acid mutations, or fusion proteins) are the driving, hallmark features of disease. Disruptions in mSWI/SNF-mediated chromatin remodeling also cause neurodevelopmental disorders such as autism and intellectual disability. As such, our lab uses a diverse collection of experimental and computational approaches to define the structure and function of these chromatin remodeling complexes, including biochemistry, biophysics, structural biology, genomics-centered methodologies (ChIP-seq, ATAC-seq, RNA-seq, others), model systems, chemical biology, bioinformatics, and computational biology. Importantly, several mechanisms we have uncovered have informed the development of new therapeutic approaches for a range of devastating cancers and other conditions. At present, we have 20 laboratory members, and a diverse collection of exciting projects at the interface of basic biology and translational medicine.

Our laboratory at the Dana-Farber Cancer Institute and the Howard Hughes Medical Institute (HHMI) is centered in understanding mechanisms of chromatin and gene regulation, with an emphasis on ATP-dependent chromatin remodeling complexes such as the mammalian SWI/SNF (mSWI/SNF or BAF) complex, which are among the most frequently disrupted molecular entities in cancer, neurodevelopmental disorders, immune conditions, and others. We use multidisciplinary approaches, integrating protein complex biochemistry, 3D structural biology, genomics and epigenomics, and systems biology to define mechanisms of chromatin regulation in disease models and primary human tissue.