Novel Drug Target Identification: We have used our functional genomics platform to identify the targets and mechanisms of action for novel anti-cancer and anti-viral drugs. Here, knockdown of the drug target is expected to sensitize a cell to its activity. As an example of this work, we recently used parallel shRNA and CRISPR/Cas9 libraries to identify DHODH as the target of a host-targeting antiviral drug, GSK983. Interestingly, each screen provided complementary information about the drug; the shRNA screen identified the target, while the CRISPR screen identified genes that interact with the target, but were missed by the shRNA screen. We are now exploiting what we have learned about this drug to improve potential antiviral therapies (collaboration with Khosla lab)

 

 

 

 

High-throughput Identification of Synergistic Drug Combinations: More recently, we have developed a strategy to target pairs of drug targets using CRISPR. With this system, we could quickly scan through ~500,000 possible sgRNA pairs (corresponding to ~21,000 drug combinations) to identify potent synergistic drug pairs that were effective in BCR-ABL driven leukemia cells. We are excited to use this strategy to find potent drug combinations in a range of cancers.