Our Research
Our interdisciplinary research program aims to uncover how cells establish and maintain their chromatin landscape and gene expression patterns, and the implications of these mechanisms for human health.
Chromatin comprises millions of nucleosomes made of DNA wrapped around histone proteins that organize our genome. Nucleosomes dynamically modulate the access to genomic DNA sequences for regulatory proteins like transcription factors and RNA Polymerase, making chromatin structure a critical player in regulating gene expression and other DNA-based processes. Differential gene regulation due to chromatin is central to why different cell types in our body function differently despite containing the same DNA, and partly contributes to epigenetic inheritance. However, this process can lead to developmental disorders and cancer when defective.
Our primary research interest is to study the mechanisms that regulate chromosomal nucleosome structure and organization, especially ATP-dependent nucleosome remodeling. ATP-dependent nucleosome remodelers are multi-subunit protein complexes that dynamically modulate DNA accessibility for transcription, replication, and repair and are essential for cell-type-specific gene expression during development. Disruptions in nucleosome remodeler functions are often found in human diseases. For example, SWI/SNF or BAF, a particular type of nucleosome remodeler, is alone mutated in over 20% of human cancers and several developmental disorders of the central nervous system.
Our lab aims to dissect the intricate biochemical mechanisms involved in regulating chromatin structure, with a focus on ATP-dependent nucleosome remodeling. Our goal is to understand how remodeler functions integrate with other chromatin regulators and chromatin-based cellular processes to establish and maintain unique chromatin landscapes that define cellular identity.
We investigate the structural and functional aspects of how nucleosome remodelers, transcription factors, and gene-regulatory proteins such as RNA Polymerase interact with chromatin.
We determine how chromatin regulators alter histone-DNA interactions in nucleosomes and modify chromatin structure at high spatial and temporal resolution.
We study how ATP-dependent nucleosome remodeling establishes new gene expression programs during cell fate changes, such as embryonic development and cancer.
We leverage the power of cutting-edge genome-wide approaches combined with in vitro biochemistry techniques to address these questions while also endeavoring to advance the field by developing novel methods for investigating dynamic protein-DNA interactions on chromatin.