Endothelium serves as a homeostatic barrier between the blood vessel lumen and the tissues, whereas impaired barrier function leads to vascular leakage in numerous diseases. Growth factors that regulate many of the functions of the blood vessels have been discovered, but their mechanisms of action are incompletely understood. This proposal will focus on a key growth factor regulating blood vessel function in homeostasis and disease, and determine, at an atomic level and via computational methods, its molecular activation mechanism of an important endothelial cell adhesion receptor. The proposal will use a multidisciplinary approach and innovative technology to develop biological binder molecules to specifically interfere with selected turning points of growth factor function using disease modeling. The fundamental new knowledge generated in the project will have impact on understanding growth factor function and its inhibition in a variety of vascular diseases.

2022

2025