Our research seeks to understand signal transduction pathways that control cell survival and death in normal and cancer cells. Based on newly discovered oncogenic signaling mechanisms, we employ a chemical biology approach to gain further insights into the molecular basis of cancer and to develop small molecule modulators for drug discovery and translational research.

Survival signaling pathway studies. We are interested in identifying mechanisms that couple survival signaling to the apoptotic machinery. One such mechanism is mediated by the 14-3-3 protein family. 14-3-3 suppresses apoptosis in part through binding to death-promoting proteins such as ASK1 and Bad. We are taking steps to dissect the roles of 14-3-3 in mitogenic and apoptotic signaling pathways. Because of its role in mitogenic signaling and tumorigenesis, 14-3-3 is used as a probe for identifying novel regulatory proteins that promote or suppress tumorigenesis.

Small molecule modulator identification for probe and drug discovery. One hallmark of cancer is the upregulation of cell survival. We are designing mechanism-based bioassays for high throughput and high content screening (HTS/HCS) of compounds for signaling modulators, such as 14-3-3 and ASK1 inhibitors. Such compounds will be developed as probes for mechanistic studies and for drug discovery.

Translational research. To translate our basic understanding of survival signaling into clinical settings, we collaborate with physician scientists to develop novel therapeutic strategies for the prevention and treatment of cancer. In addition, we collaborate with chemists to develop new anticancer agents that can modulate survival pathways with the hope of moving more effective therapeutics into the clinic.