Defining the role of hemodynamic forces in shaping cardiovascular system morphogenesis.

Cardiac contractions, which propel blood throughout the organism, are essential for vertebrate development as well as the maintenance of physiological processes throughout the organism’s lifespan. Cardiovascular diseases are a major health challenge and the leading cause of mortality worldwide. However, the mechanisms governing these conditions remain poorly understood.

Hemodynamic forces generated by the blood flow are critical to shape organogenesis, such as the differentiation and remodeling of endothelial cells, which line the vessels, during cardiovascular morphogenesis.

Although several blood flow mechanosensors have already been identified, their precise mechanism of action in subpopulations of endothelial cells remains to be uncovered.

By integrating my dual expertise in blood flow mechanosensation and genetic tool optimization, I will explore these questions using the zebrafish, a leading model of cardiovascular genetics, through the following aims: 1) Determine venous fate repression in endocardial cells, a specialized type of endothelial cells. 2) Extend my endocardial focus to vascular flow-sensitive endothelial populations, the blood-brain barrier, and the caudal vein. 3) Optimize genetic tools to manipulate gene function in the context of cardiovascular disease models.

I anticipate that this proposal will shed new light on the role of blood flow in endothelial patterning, providing novel therapeutic targets to treat cardiovascular diseases.