The extracellular matrix and the clonogenic survival benefit of CCM3-/- endothelial cells as new therapeutic targets for cerebral cavernous malformations

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The recently identified clonogenic survival benefit of CCM3-/- endothelial cells has the potential to open up a new perspective on CCM pathogenesis. Since this effect of long-term CCM3 inactivation is still insufficiently understood, the project aims to clarify the molecular basis of apoptosis resistance of CCM3-deficient endothelial cells and to identify new drugs to inhibit this pathway. Thus, the project also intends to provide a better understanding of the regulation of angiogenesis and vascular remodeling. In vitro co-culture and innovative three-dimensional organoid models which mimic the in vivo situation will be established. These novel assays can be used for high-throughput testing of pharmacological agents and could contribute to shortening therapy development for vascular diseases. Additionally, the role of a novel candidate protein of the extracellular matrix will be addressed with these assays.