Cerebral vascular malformations and therapeutic strategies

Cerebral Cavernous Malformation (CCM) is a vascular disease affecting the brain that can be either inherited or sporadic.

In general, patients with sporadic CCM usually develop a single malformation while familial CCM is characterized by the presence of multiple CCM lesions that increase in number and size with patient’s age. The CCM lesions cause cerebral hemorrhages due to their fragility. Hemorrhage will trigger hemostasis causing platelet activation and blood coagulation.

To date there is no pharmacological treatment available for CCM patients.

The aim of this proposal is to increase the knowledge in CCM disease on a molecular level and to find new therapeutic strategies, with a specific focus on the link to inflammation and immunity; immunothrombosis in CCM.

For this, we have access to human CCM biopsies, high quality in vivo and in vitro models of CCM including coagulation activation and microfluidics.

We also aim to understand the vascular lesions’ effect upon the cells of the neurovascular unit, specifically the pericytes but also the surrounding brain parenchyma.

We will perform advanced single-cell RNA sequencing analysis, ATAC sequencing on isolated brain endothelial cells, spatial transcriptomics on sectioned material, proteomics of both human and mouse derived biopsies and plasma/serum samples.

With gained knowledge we aim to find new potential pharmaceutical drugs that affect lesion growth and immunothrombosis while protecting the brain parenchyma.