Grant: Project Grant

One of the most important class of molecules involved in embryonic development and adult tissue homeostasis are the Wnt family of secreted proteins. In humans, 19 Wnt proteins activate 10 cell surface Frizzled receptors. We have developed antibodies that are very specific for Frizzled receptors and recently made an important discovery to make these antibodies activate the Frizzled receptors. These molecules therefore act as synthetic Wnt ligands. One of the Ten Frizzled receptors, Frizzled-4, is particularly important for the development of the brain and retina vasculature in controlling the permeability of the endothelial cells. Since the ontogeny of several diseases such as diabetic retinopathy, stroke, multiple sclerosis and Alzheimer is thought to be rooted in defects in endothelial cell permeability, we will test if activating the Frizzled-4 receptor will promote endothelial cell barrier function and decrease permeability. If successful, these new agents could represent a new class of drugs to treat these diseases.