Most modern diseases originate from vascular dysfunction. Unhealthy vessels either fail to control proper transport into tissues or fail to organize a vascular network with efficient flow. Selective transport and vascular network organization are orchestrated by the innermost lining of cells, called the endothelial cells. Throughout the vascular network, endothelial cells sense the local supply and demand for blood flow and respond by allocating it as efficiently as possible. However, we still do not understand how the endothelial cells sense changes in blood flow, interpret these cues in the context of their microenvironment, and respond to modify vessel structure/function. As such, the Coon lab studies endothelial cell responses to the forces of blood flow, called mechanotransduction, to alter vascular architecture and inflammatory status.

Our lab studies vascular mechanotransduction across scales ranging from molecular to cellular to systems to tissue. In vitro, we combine hemodynamic flow systems with fluorescent reporters, biochemical, or molecular analysis to precisely identify and characterize mechanotransduction pathways. In vivo, we combine mouse genetic models with advanced imaging techniques to perturb mechanotransduction and visualize network organization and vessel functions.

Our research previously identified endothelial mechanosensory complexes and mechanotransduction pathways that mitigate risk for atherosclerosis. These include those that promote cell alignment, suppress NF-kB-dependent inflammation, and stimulate healthy expression of the anti-inflammatory, anti-thrombotic transcription factors KLF2 and KLF4. Our current research aims to identify new mechanotransduction pathways that control A) switching between pro- and anti-inflammatory states related to atherosclerosis and vascular dementia and B) switching between stabilized and remodeling vessels related to genetic diseases of uncontrolled vascular growth (malformations), development, and regenerative medicine.