Uncover the pathogenesis of brain arteriovenous malformation

In this proposal, we will test our hypothesis that mutant ECs cause bAVM formation and progression through stimulating excessive angiogenesis, impairing pericyte function and induction of inflammation. We will show that mutant ECs undergo clonal expansion and release angiogenic factors to stimulate the proliferation of adjacent normal endothelial cells. We will also show that mutant EC impair pericyte function through reduction of PDGFB mediated ANG1, TGFb1 and PDGFRb expression in pericytes and that mutant EC drives microglia activation, macrophage, and lymphocyte infiltration through induction of EC-inflammation. The overarching goal of this project is to identify new therapeutic targets.