While many of the same chromatin modifying complexes present in humans are also present in lower organisms such as drosophila, there has been considerable expansion of subunits during vertebrate evolution, substantially increasing both the compositional and functional diversity of these complexes. This gene expansion is important for precise gene control required for the cell type diversification observed in the more complex tissues and organ systems present in higher order organisms. As a corollary, many of the subunits of these chromatin modifying complexes have recently been found to be mutated or overexpressed in particular cancer types. Part of understanding the roles these subunits play in cancer will involve understanding the cell type specific roles these individual subunits play in defining cell state.
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We study two diverse protein complexes with cell type specific expression of subunits, the BAF (human SWI/SNF) chromatin remodeling complex and the Polycomb repressive complex 1. More specifically, the focus of our lab is to decipher the role of chromatin targeting subunits on the overall function of chromatin modifying complexes important in tumor suppression and oncogenesis. We use a combination of cellular biology, molecular biology, genomics, proteomics, and biochemistry to understand how chromatin targeting and transcriptional regulation is altered during cancer.
PBRM1-mediated targeting of the PBAF chromatin remodeling complex
CBX-mediated targeting of Polycomb Repressive Complex 1
