Our group is using large-scale human cell genetic screens and functional genomics together with high-throughput sequencing to identify critical genes in cancer progression, genome maintenance and therapeutic resistance. We use genome engineering to create isogenic cell pairs modeling cancer progression in cell culture one step at a time. The cell lines are used in synthetic lethality genetic screen to uncover genes whose expression is critical for the growth of the cell line bearing the oncogenic alteration but not the control isogenic cell line. The same settings are used to identify genes whose inhibition sensitize the target cells to drugs developed against specific oncogenic drivers or on the contrary, conferring resistance to this newest generation of drugs that are the tools of today's precision medicine. We hope to capture and address significant therapeutic challenges with our in vitro models and we seek to establish their relevance through interactions with clinicians.​