Prof. Dr. Matthias Rath
Phone: +49 3834 / 86 53 96
The focus of our research group lies on cerebral cavernous malformations (CCM) which are sometimes also called cavernous angiomas or cavernomas. These enlarged endothelial channels can be found in the venous-capillary bed of the central nervous system. They lack supporting pericytes and smooth muscle cells and tend to bleed. Haemorrhages into the neighbouring brain parenchyma may cause recurrent headaches, seizures and stroke-like symptoms.
CCMs may occur sporadically or in an autosomal dominant form. Familial CCM is caused by loss-of-function germline variants in one of three genes: CCM1/KRIT1, CCM2/OSM and CCM3/PDCD10. The prevalence of symptomatic carriers of a pathogenic CCM1, CCM2 or CCM3 variant is approximately 1:5,400-1:6,200. The first symptoms are usually reported in the second to fifth decade of life. However, one third of CCM patients are minors and 20% are younger than 10 years. Analyses of human CCM tissue samples with ultra-sensitive next generation sequencing technologies and immunohistochemistry have supported the hypothesis of a genetic two-hit mechanism in CCM formation (Figure).
The aim of our research group is to understand the pathogenesis of hereditary vascular malformations. For this purpose, we use next generation sequencing technologies and CRISPR/Cas9-mediated genome editing. Specifically, we have modelled the situation in human CCMs by highly efficient inactivation of CCM1, CCM2 or CCM3 in human endothelial cells using crRNA:tracrRNA:cas9 ribonucleoprotein transfection.
In new two- and three-dimensional cell culture models, we now try to clarify why endothelial cells have a survival advantage after inactivation of CCM1, CCM2 or CCM3 (Figure). By testing different pharmacological agents, we want to identify a new therapeutic approach. Pharmacotherapy is urgently needed for CCM patients for whom surgical resection is not an option.
Prof. Dr. Ute Felbor
Phone: +49 (0)3834 / 86 53 70
e-mail: ute.felbor@med.uni-greifswald.de
Prof. Dr. Matthias Rath
Phone: +49 3834 / 86 53 96
e-mail: Matthias.Rath@med.uni-greifswald.de
Dr. Dariush Skowronek
Phone: +49 3834 / 86 53 75
e-mail: Dariush.Skowronek@med.uni-greifswald.de
Dr. Robin Pilz
Phone: +49 3834 / 86 53 99
e-mail: RobinAlexander.Pilz@med.uni-greifswald.de
Dr. Christiane Much
Phone: +49 3834 / 86 53 68
e-mail: Christiane.Much@med.uni-greifswald.de
Valeriia Saenko, M. Sc. (PhD student)
Tel.: +49 (0)3834 / 86 53 99
E-Mail: Valeriia.Saenko@med.uni-greifswald.de
Lara Mellinger (MD student)
Tel.: +49 (0)3834 / 86 53 80
Barbara Sendtner (MD student)
Phone: +49 3834 / 86 53 80
