Filamins stabilize a transmembrane complex to initiate angiogenesis Grant uri icon


  • Endothelial cells are guided by hemodynamic forces and biochemical signals during angiogenesis, which is new blood vessel growth from pre-existing structures. Angiogenesis is crucial for tissue repair following myocardial infarction and stroke. Thus, a better understanding of the key molecular signals that regulate activation of the angiogenic switch could aid in healing of cardiac or brain tissue. This proposal will test the hypothesis that filamins are recruited to the endothelial surface to stabilize a complex of mechanosensitive transmembrane receptors and MT1-MMP at the endothelial surface and generate downstream second messengers needed to transition from an adherent to an invasive phenotype. The studies included here use a balanced approach of in vitro sprouting human endothelial cells that is amenable to dissecting molecular signals activated when sprouting is initiated, along with an in vivo model of intersegmental vessel formation that will be manipulated genetically using CRISPR/Cas. Overall, these studies are expected to uncover a hierarchical signaling pathway that precisely regulates the angiogenic switch by connecting pro-angiogenic stimuli to control of transmembrane receptors and matrix proteolysis. These studies will contribute to our long-term goal of and improved understanding of the molecular signals that initiate sprouting angiogenesis. (AHA Program: Grant-in-Aid)

date/time interval

  • 2016 - 2017