Finding new therapeutic targets

The ability to do saturating knockout screens on cancer cell lines is transforming cancer genetics. With pooled library CRISPR-Cas9 screens, we are now able to comprehensively define which genes are essential for cellular proliferation across all backgrounds ("core fitness genes"), and differentiate them from those genes required only in the presence of a particular oncogenic driver or genetic background ("context fitness genes"). Both sets of genes harbor potential therapeutic targets and information about therapeutic efficiency.

Core vs. context fitness genes

Functional genomics of cancer

Cancer cells, unlike normal cells, do not require external growth signals to proliferate, and resist signals to stop replicating.  These well-known "hallmarks of cancer" are readily studied in cell lines, but vary widely across tissues and subtypes.  Through understanding which pathways are required in which genetic and environmental contexts, we hope to gain a greater understanding of why some mutations are more common in particular tumors--leading to better predictive models of both cancer occurence and therapeutic response.