The Regulation of Notch Signaling by Src Kinase and Polyphenolic Compounds

Cellular signaling pathways provide cells with the means to sense their environment and communicate with other cells. The Notch signaling pathway is comprised of a set of protein machines which work in unison to coordinate cellular processes in response to stimuli coming from neighboring cells and changing microenvironmental conditions. Notch signaling is an important mode of cellular communication which is crucial to many processes involved in development and disease. During Notch activation, information about the extracellular environment is fed into the cell and relayed to the nucleus through a number of biochemical processes. The information-rich messages carried by Notch signaling is used to make genetic decisions through alteration of gene expression which ultimately controls cellular physiology. Critical to Notch function, are a series of regulatory steps which serve as points of integration where other sources of information are fed into the Notch pathway. In this dissertation, I describe five years of work, where I sought to discover new ways in which Notch signaling is regulated. Through this work, I have come to regard Notch signaling as a highly tunable mode of cellular signal transduction, which harmonizes extracellular cues in order to orchestrate cellular behavior. Here, I described a series of experiments, performed by myself and my collaborators, which have served to uncover novel regulatory mechanisms by which Notch signaling is controlled. Through bettering our understanding of this critical mode of cellular communication, we prime science with the knowledge which may one day fuel the development of new therapeutic strategies to combat Notch-related diseases