We leverage advances in genetic screening to identify in a high throughput manner novel genes that play vital roles in maintaining genomic integrity. In addition to whole-genome CRISPR libraries, we have several small, focused libraries that we are employing to identify novel factors and genome maintenance mechanisms that function in different contexts. These screens are often performed following perturbation with low doses of various replication stress-inducing agents. These screens allow us to identify several new genes and mechanisms of genome maintenance and have led to the following projects:
Our recent whole-genome cisplatin sensitivity screens (see publication below) identified up to 400 high confidence hits, many of whom have not been previously characterized. These hits are currently being characterized in the lab. In addition to targeting protein-encoding genes, we also have libraries that target several lncRNAs. There is still very little known about how lncRNAs in general function. We are interested in extending our high-throughput approaches to identify, validate and characterize the role of lncRNAs in genome maintenance. These efforts will lead to significant new insights into their role(s) in cancer.