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

• Applicant: Professor Dr. Matthias Rath
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Human Genetics
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 383067719

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.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Ute Felbor