New Investigator Research Grant Program

Blood cell cancers often bear mutations in STAT3. This protein is normally beneficial but, when overactive, becomes a cancer ‘driver’. More than 150 relevant mutations have been identified but only a handful have been studied in any detail. Thus, it remains unknown how mutations alter STAT3 activity to drive blood cancers.The same can be said of other oncogenes. Our ability to identify potentially dangerous mutations far exceeds our ability to appraise them. The proposed research directly engages this problem. We have devised an experimental platform that enables us to study all known STAT3 mutations at once in unprecedented detail. This platform is scalable, new mutations can be easily added, and adaptable, other cancer drivers can be similarly addressed. It can also be used to screen drugs across vast mutant rosters, enabling discovery of both common and mutant-specific vulnerabilities. This research will advance basic understanding of how STAT3 drives blood cancers and inform treatment options for patients with STAT3 mutations and/or hyperactivity.