Grant: Operating Grant

Helicases are molecular machines that utilize energy to remodel DNA and RNA. Based on similarities among members of this family of proteins, they can be divided into several superfamilies. One of these, called Superfamily 2, consists of a group of proteins that are thought to be involved in regulating many aspects in the flow of genetic information from DNA to protein. Despite this central role in biology, little research has been done on this class of gene expression regulators to systematically investigate their deregulation in cancers or to explore their potential as anti-cancer drug targets. My lab has performed a genetic screen to identify new tumor suppressors among RNA helicases. This screen was performed in vivo in a pre-clinical mouse lymphoma model by decreasing the expression of each helicase and we identified two proteins, DDX3X and DDX28, as novel tumor suppressor genes. We propose herein to unravel the molecular mechanism by which DDX3X and DDX28 act to suppress cell growth. We also propose to validate our results in human tumors. Our preliminary results have identified novel tumor-specific vulnerabilities and pathways against which molecular-targeted therapeutics could be developed.