The capacity to integrate genomic and transcriptomic features of cancer cell line models with functional genetic perturbation performed at genome-scale has yielded an unprecedented ability to precisely map the molecular contexts in which cancers display specific (and often unexpected) molecular vulnerabilities.

Paralog lethality across cancers: Redundant essentiality between paralog genes may be therapeutically exploited when one of two copies of an essential paralog pair is somatically deleted in cancer. We have recently reported several such paralog pairs, including the example of MAGOHB, a component of the exon-junction complex that proves essential to maintaining RNA surveillance when its paralog, MAGOH, is somatically deleted.

By performing genome-scale genetic screening in models of genitourinary cancer, we aim to uncover novel and therapeutically tractable molecular targets that can inspire the development of the next-generation of therapies for these cancers.

Target discovery in the AR pathway in prostate cancer:
Via genome-scale genetic screening in models of prostate cancer, we recently identified the protein arginine methyltransferase 1, PRMT1,  as a novel regulator of androgen receptor signaling and a potential therapeutic target in prostate cancer. This provides preclinical support for the testing of PRMT inhibitors together with AR antagonists in advanced prostate cancer.

We are applying similar approaches to systematically dissect the vulnerabilities of other genitourinary cancers.