Title: Combining single-molecule imaging and statistical analysis to study the organization of VEGF receptors on the cell surface

Speaker: Khuloud Jaqaman, Department of Biophysics, Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center

Abstract: There is mounting evidence that cell surface receptor organization plays an important role in cell signaling. We are particularly interested in addressing questions related to cell surface receptor organization in the context of angiogenesis signaling in endothelial cells, with particular focus on the receptor tyrosine kinase VEGFR2 (Vascular Endothelial Growth Factor Receptor 2). Through single-molecule imaging and statistical analysis, we found that mobility and interaction heterogeneity of VEGFR2 on the surface of endothelial cells leads to multiple, co-existing sequences of steps for its activation by its ligand VEGF. Additionally, by developing a 3-color conditional colocalization analysis method, we found that VEFGR2 interactions with its downstream adapter TSAd are enhanced at focal adhesions, to which VEGFR2 signals upon activation. Altogether, these studies are yielding quantitative insight into the complex landscape of VEGFR2 organization and interactions and its role in VEGFR2 signaling.