Interrogation of Genetic Dependencies in Renal Cell Carcinomas.

The project involves establishing a Cas9-Cas12a CHyMErA-based combinatorial CRISPR screening platform, conducting systematic screens across diverse environmental and genetic RCC contexts using a genome-wide CRISPR knockout library, validating screen hits, elucidating underlying molecular mechanisms influencing cell fitness, assessing the conservation of these vulnerabilities across additional RCC models and other cancer types, and conducting chemogenetic screens to uncover genetic modifiers that modulate sensitivity to small-molecule inhibitors targeting metabolic dependencies.