Welcome to the lab of Charles W. M. Roberts, MD, PhD
The Roberts laboratory studies the SWI/SNF (BAF) chromatin remodeling/tumor suppressor complex. We first began studying the complex over a decade ago when it was shown that the SNF5/SMARCB1/INI1/BAF47 subunit was specifically mutated in nearly all cases of malignant rhabdoid tumor, a highly aggressive and lethal cancer of early childhood.
Recent data now demonstrate that at least eight separate subunits of this complex are recurrently and specifically mutated in a wide variety of cancers, collectively occurring in 20% of all human cancers. Consequently, the SWI/SNF complex is the most frequently mutated chromatin regulatory complex with a mutation frequency that exceeds many classical tumor suppressors and oncogenes.
The SWI/SNF complex, which utilizes ATP hydrolysis to remodel chromatin, has a role in epigenetic regulation via nucleosome remodeling-based control of lineage-specific transcription. We have demonstrated key roles for SNF5, a core member of this complex, in tumor suppression using genetically engineered mouse models.
We hypothesize that the SWI/SNF complex is a master regulator of gene expression via its effects on chromatin structure and seek to identify the mechanisms by which perturbation of this ATPase chromatin remodeling complex leads to cancer formation. Given the dramatic nature in which inactivation of SNF5 drives cancer formation, characterization of this complex will lead to insights into the mechanisms of tumorigenesis.
To this end, we are using mouse modeling combined with molecular, cellular and biochemical approaches to characterize this newly appreciated mechanism of tumor suppression and to identify novel therapeutic targets. Our work principally focuses upon basic and translational research, but has now led to an open clinical trial as well.
We have several openings at the staff and postdoctoral level.