Our laboratory research program is centered in understanding the structure and function of ATP-dependent chromatin remodeling complexes, with emphasis on the mammalian SWI/SNF (mSWI/SNF or BAF) family of assemblies. Using a multidisciplinary set of approaches ranging from protein biochemistry and structural biology to functional genomics and systems biology, we aim to understand the mechanisms governing mSWI/SNF complex activity and genomic targeting in both normal and disease states. Human genetic sequencing efforts performed over the past several years have unmasked the major contributions of these chromatin regulators to human disease. Indeed, mutations in mSWI/SNF complex genes are present in over 20% of human cancers, including several rare cancers in which mSWI/SNF subunit perturbation is the hallmark and driving feature, occurring in 100% of cases. In addition, mSWI/SNF genes are frequently mutated in neurodevelopmental and intellectual disability syndromes, including autism, as well as immune conditions. Functional studies have revealed the essential roles of these complexes in biologic processes such as viral infection, T cell activation and specialization, among others. These studies underscore the important roles for mSWI/SNF complexes in regulating timely and appropriate chromatin accessibility and gene expression during cell and tissue development. Our lab pursues biochemical, structural, and functional studies across a range of in vitro, cell-based, and organoid and murine model systems coupled with advanced bioinformatics approaches and systems biology to understand mechanisms governing mSWI/SNF complex function and to inform new therapeutic opportunities.
Ongoing studies in the laboratory aim to determine the mechanisms by which subunit perturbation and subsequent structural changes misdirect ATP-dependent chromatin remodeling complex targeting and activity genome-wide. In addition, we aim to define the constellation of chromatin landscape features that directly or indirectly impact mSWI/SNF complex function, associated kinetics and dynamics, and the mechanism of antagonism with repressive chromatin regulatory complexes such as polycomb repressor complexes, enabling a comprehensive understanding of chromatin topology and gene regulation driven by this family of ATP-dependent chromatin remodeling machines.
Dana Building, Room 620
450 Brookline Avenue
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