Charles Roberts

Charles Roberts established the mechanistic basis for EZH2 inhibitor therapy in SMARCB1-deficient cancers, demonstrating that loss of the SWI/SNF chromatin remodeling complex creates an epigenetic dependency on EZH2-mediated H3K27 trimethylation that can be therapeutically exploited. His work on rhabdoid tumors and epithelioid sarcoma provided the scientific foundation for the FDA approval of tazemetostat (Tazverik), the first EZH2 inhibitor approved for cancer treatment. He has elucidated how SWI/SNF mutations in over 20% of human cancers create vulnerabilities to chromatin-targeted therapies. His research defines the paradigm of epigenetic synthetic lethality between chromatin remodeling defects and histone modification dependencies.