Speaker

Jan Kitajewski, PhD, University of Illinois Chicago

Abstract

Notch signaling directs cellular responses during normal development across an evolutionarily wide span of organisms and is implicated in disease pathogenesis in humans. In mammals, four Notch receptors and five Notch ligands are predominantly responsible for a range of biologic processes that drive cell fate determination, and this contributes to mammalian development and tumorigenesis. Angiogenesis has been one of the most well studied role of Notch proteins. Normal vascular endothelial cells principally express Notch1, Notch4, and Notch ligands Jagged1 and Dll4. Extensive prior work has defined the critical role of Dll4-Notch1 in angiogenesis via the regulation of endothelial tip and stalk cell identity leading to formation of nascent vessels. Here, we report that blocking Notch signaling using Notch Decoys, targeting either Dll4 or Jagged1, blocks tumor growth while impacting the tumor vasculature via diverse mechanisms. These studies establish that Jagged1 promotes tumor angiogenesis while Dll4 restricts endothelial sprouting in tumor vasculature. We also discuss new information about the impact of the Notch ligand, Jagged1, on the process of metastatic spread via vasculature.

In-person and virtual event

In-person location: Room 2220, BME building (Map)

Online: Zoom link

Join via: ID: 915 3281 4691 (Passcode: 835156)