Deciphering BAF Assembly for Pediatric Cancer Therapy
Synopsis: The adenosine triphosphate (ATP) dependent multi-subunit assemblies such as (BRG1/BRM-associated factors) complexes utilize ATP hydrolysis energy to reorganize chromatin architecture and facilitate genomic accessibility to transcription factors.
However, in pediatric cancers, both assembly and recruitment of the BAF complexes are disrupted by mutations, deletions, and overexpression of individual subunits, causing aberrant rewiring of BAF-mediated signaling. Moreover, aggressive childhood cancers often display molecular partnerships between defective BAFs and chimeric transcription factors. If successful, this proposal will inform novel approaches to abolish the tumor-promoting functions of aberrant BAFs.