STRUCTURE AND FUNCTION OF TRANSMEMBRANE RECEPTORS
My primary scientific interest is to uncover the molecular logic of biological signaling pathways in normal and pathophysiologic states, and to harness these findings for the development of molecularly targeted therapies. Within this broad area, our current studies emphasize structure-function correlates in normal and oncogenic signaling, with a major focus on transmembrane signaling and Notch signal transduction. My laboratory defined the structural basis for assembly of Notch transcriptional activation complexes, determined the molecular mechanism of autoinhibition of Notch receptors, and demonstrated that mechanical force delivered by the signal sending cell is required to activate physiologic Notch signals. Ongoing work in our group is centered on regulatory mechanisms that remain unresolved both in Notch signaling and in other systems.