Cellular models represent powerful tools for the study of genetic variation in disease, but standard collections of such models are primarily useful for the study of common variation. Most observed genetic variants in cancer are rare, however, with many variants being observed in only a single tumor. In order to benefit all cancer patients, we aim to study the impact of such rare variation in cancer. To do this, we are developing new genome editing approaches that allow the high-throughput editing of genomes with single base resolution, and that are compatible with next-generation single cell readouts in both cancer and primary cell models.

Publications:

Hanna RE, Hegde M, Fagre CR, DeWeirdt PC, Sangree AK, Szegletes Z, Griffith A, Feeley MN, Sanson KR, Baidi Y, Koblan LW, Liu DR, Neal JT, Doench JG. Massively parallel assessment of human variants with base editor screens. bioRxiv. 2020 May 17.