Priyanka Verma, PhD

Assistant Professor, Dept. of Medicine, Division of Oncology

WashU Medicine

Talk Title: Deep mutational scanning of a chromatin remodeler uncovers a new therapeutic strategy for BRCA-mutant cancers

Abstract: We have identified that the loss of ATPase activity of a chromatin remodeling enzyme, Amplified in Liver Cancer 1 (ALC1), is synthetically lethal in BRCA-mutant cancers. By pursuing a deep-mutational scanning of the ATPase domain of ALC1 we have uncovered surface-exposed pockets that are critical for synthetic lethality, not conserved amongst other ATPases, and exhibit minimal mutational tolerance, limiting the chances for acquired resistance. Together, our studies provide a strong foundation for the development of a safe and potent therapeutic strategy for combating BRCA-mutant cancers which have few to no curative options.

Host: Dr. Gabor Egervari