Congenital Vascular Malformations (CVM) are a group of diseases characterized by an inborn, localized defects of vascular morphogenesis. Occurring mainly on the face or other highly visible part of the body, the presence of CVM can cause emotional and social problems. Moreover, some malformations are painful or even life-endangering. Current treatments do not achieve optimal or long-lasting results. Thus, there is a pressing need for therapies that are more effective for these disfiguring lesions. Currently, the cellular components of the CVM have not been isolated and analyzed, and there is no animal model for most CVM. One attractive treatment strategy is to induce transdifferentiation of the endothelial cells (ECs) of the lesion. Transdifferentiation is the reprogramming of one specialized cell type into another, without reversion to pluripotent cells.The goal of my research is to isolate and characterize the EC, the major cellular component of the vascular malformations in order to develop targeted therapy for these lesions. EC and pericytes will be isolated from CVM tissues. We will perform extensive mutational analysis and epigenetic profiling of these primary cells in order to identify any abnormalities in their developmental path. Also, using novel techniques derived from the stem cell field, I will aim at inducing transdifferentiation of the l EC by forced expression of transcription factor pools.My hypothesis is that reprogramming the EC lining the vasculature of the lesion to a mesenchymal phenotype will lead to obstruction of these vessels and cessation of blood flow, resulting in significant improvement. Importantly, insights gained from this research will have wide implications for the vascular biology field. Thus, this project is novel and innovative.Having both extensive research experience with the study of angiogenesis and clinical expertise in Dermatology, I’m well-suited for the conduction of this project.