Coordinatore | MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER
Organization address
address: TEL HASHOMER SHEBA MEDICAL CENTER contact info |
Nazionalità Coordinatore | Israel [IL] |
Totale costo | 100˙000 € |
EC contributo | 100˙000 € |
Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
Code Call | FP7-PEOPLE-2010-RG |
Funding Scheme | MC-IRG |
Anno di inizio | 2011 |
Periodo (anno-mese-giorno) | 2011-03-15 - 2015-03-14 |
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MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER
Organization address
address: TEL HASHOMER SHEBA MEDICAL CENTER contact info |
IL (RAMAT GAN) | coordinator | 100˙000.00 |
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'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.'
European researchers are investigating an innovative therapeutic approach based on the conversion of endothelial cells to another cell type.
Congenital vascular malformations (CVM) are a group of inborn disorders associated with vein or artery defects. These often induce disfiguring lesions in the face and are a great cause of pain and social distress to the affected individuals. Currently there is no definitive therapy for CVM.
A better characterisation of the cellular components of the CVM is required to induce transdifferentiation of the endothelial cells (ECs) in the lesion. The scope of the EU-funded CVM THERAPY (Angiogenesis research to improve therapies for vascular malformations) project is to isolate and characterise the Ecs in the vascular malformations to therapeutically target these lesions.
Researchers isolated capillary, venous and lymphatic Ecs from various biobanked sporadic CMV cases. They used a real-time cellular analysis system to analyse the proliferation of EC from malformations as well as their migratory and angiogenic properties. Preliminary data indicate distinct alterations compared to their normal counterparts.
To selectively halt blood supply in various diseases, scientists are in the process of differentiating Ecs to mesenchymal stem cells, a well-known developmental phenomenon. Emphasis is also being given to the identification of the basic signalling pathways and the transcription factors implicated in these transdifferentiation processes.
From previous work, CVM THERAPY researchers had discovered that TGF-beta drove the endothelial to mesenchymal transdifferentiation and are currently exploring the use of this cytokine to drive CVM EC differentiation. Additionally, they are exploring the utilisation of the transcription factors - serum response factor and myocardin, which are essential for smooth muscle cells.
Taken together, the activities of the CVM THERAPY project demonstrate how the characterisation of Ecs could lead to the development of targeted drugs for CVMs.
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