ATP-dependent chromatin remodeling complexes

 

Chromatin remodeling complexes play an essential role during normal development and disease by regulating chromatin dynamics. Four major subfamilies of ATP-dependent chromatin remodeling complexes have been identified. This includes imitation switch (ISWI), INO80, chromodomain helicase DNA-binding (CHD) and switch/sucrose non-fermentable (SWI/SNF). In the past decade, studies in human cancers have identified recurrent genetic and epigenetic alterations that modulate their expression and function. Yet, their role in promoting cancer development and modulating responses to immunotherapy and targeted therapies remains poorly delineated.

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To study the function of ATP-dependent chromatin remodeling complexes in cancer, we leverage a series of novel biological models including genetically engineered mouse models (GEMMs), cellular models and patient derived xenografts (PDXs). We also apply cutting-edge bulk and single cell transcriptional and epigenomic approaches (e.g., CUT&RUN, CUT&Tag, RNA-seq, ATAC-seq) to elucidate the mechanisms by which ATP-dependent remodelers regulate cancer development and therapeutic responses. Finally, we take advantage of functional genomic technologies (e.g., CRISPR/Cas9, ORFs, RNAi screens) to identify novel therapeutic targets for tumors that harbor genetic alterations in ATP- dependent chromatin remodelers.