Project Grant R37CA296409

This federal Project Grant award from the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) provides $442,089 to Yale University to conduct research on regulatory pathways compromised by PRMT5 inhibition in cancers with MTAP loss. The project aims to identify key components of the PRMT5 axis that impair cell viability upon PRMT5 inhibition, and define pathways that can restore viability. The research will examine the impact of top-scoring gene products on DNA damage response, R-loop formation, and homologous recombination pathways, using proteomic, biochemical, and genetic approaches to understand how these proteins intersect with the PRMT5 axis. Successful completion of the project will identify processes dysregulated by PRMT5 inhibition that impair cell viability, delineate molecular mediators of these processes, and provide insights about mechanisms of DNA damage response regulation. The findings may also identify additional therapeutic targets in the PRMT5 pathway for cancers with MTAP loss.