Damon Runyon Researchers

Cancer growth is often driven by the dysregulation of a class of proteins known as small GTPases. These proteins act as molecular "on/off" switches that regulate critical cellular processes such as cell division and movement. However, in cancer, these molecular switches often become stuck in the "on" state due to mutations that hamper GTP hydrolysis, the reaction that turns "off" the GTPase switch. One notable example is the family of GTPases encoded by Ras genes, which are mutated in 30% of all human cancers. Dr. Zhang's research aims to design small molecules that inactivate these mutant GTPases by accelerating GTP hydrolysis. His research will provide a new therapeutic mechanism for the treatment of mutant Ras-driven cancer for which no direct therapies are yet available. The design principles may also apply to the modulation of other small GTPases whose overactivation underlies cancer progression.