Investigating tyrosine phosphorylation of Notch proteins

Project Summary
Extracellular matrix, integrins, and Notch collectively regulate a host of normal and pathological
cellular activities. Evidence emerging from our preliminary studies shows that these cellular
entities are coordinated into a signaling mechanism that has not been previously observed. The
implications of our observation are broad and likely to have deep impacts on our understanding
of cell interactions within cellular microenvironments as well as cellular behaviors in a range of
normal and pathological scenarios. In this renewal application, we investigate the hypothesis
that Notch tyrosine phosphorylation regulates angiogenesis. To address this hypothesis, we
have proposed two aims that dig deeper into the molecular regulation of Notch activity through
tyrosine phosphorylation by Src kinase, and to understand how Notch tyrosine phosphorylation
impacts angiogenesis and vascular function. Throughout these studies and in the spirit of the
AREA program, we will engage high school, undergraduate, and graduate students to build
scientific confidence and teach skills these students will require in order to pursue careers in
science. At the conclusion of our studies, we will have accomplished two important milestones
towards understanding this novel regulatory mechanism. Specifically, we will have unraveled
many molecular details describing how Src controls Notch, and we will have defined the
importance of this signaling cascade to vascular biology. Since both Notch and vascular biology
operate in a wide variety of normal and disease states, our work is highly relevant to the
promotion of human health.

Grant Number: 1R15HL167130-01
NIH Institute/Center: NIH
Principal Investigator: Allan Albig