The Wnt pathway was shown by us and others to provide a major signaling cue for vascular barrier formation in the brain. The adherens junction (AJ) protein β-catenin is known to play a crucial role in „canonical“ Wnt signaling, in which activation of frizzled receptors by Wnt-growth factors stabilizes β-catenin in the cytoplasm, leading to its translocation to the nucleus and to target gene transcription via a bipartite transcription factor formed by β-catenin and lomphoid enhancer factor (Lef) / T-cell factor (TCF) (see Scheme 1). In particular, the role of endothelial Wnt signaling for physiological vessel function and for establishment of vascular hetrogeneity within the CNS is subject of our research. Herein we are focussing on the circumventricular organs (CVOs) that are considered as communication sites between the CNS and the periphery, being invovled in major function such as regulation of thirst fluid homeostasis. Another important aspect of our interest is the identification and validation of endothelial specific Wnt target genes in the BBB. The dual role of β-catenin as a scaffolding protein on the one hand and as a transcription factor on the other makes it an interesting and challenging protein to be studied during vascular development and pathological angiogenesis, like in stroke or malignant brain tumors. Furthermore, we want to shed some light on the role of the Wnt pathway in the formation and/or progression of epileptic seizures. In particular, we are interested in this respect in the crosstalk of Wnt/β-catenin with other pathways and inflammatory reactions. To study β-catenin and Wnt signaling in the vascular endothelium of the CNS, transgenic mouse lines (reporter and knock-out systems), mouse models of CNS diseases and in vitro culture of primary endothelial cells - also in co-culture with other cell types of the neuro-vascular unit - are employed.
Below you'll find and overview and a brief description of the currently running projects. The common theme of the projects is related either to the brain vasculature and the blood-brain barrier (BBB) or to the Wnt/β-catenin pathway. Click on the icons to dive deeper into individual subjects.
Vascular heterogeneity in the CNS
the project deals with the regulation of vascular differentiation in regions of the CNV that do not develop a BBB phenoty, focussing on the circumventricular organs
Regulation of BBB function in epilepsy
Mesial temporal lobe epilepsy (MTLE) coincides with functional impairment of the blood-brain barrier (BBB). This project intents to explore the molecular alterations at the BBB, and their contribution to the formation and/or progression of the disease.
In ageing western societies, Alzheimer's disease (AD) and dementia is an increasing cause morbidity and mortality. This project intents to explore the molecular alterations of AD and ageing on the brain vasculature
Cell fate decision in the hematopoietic system
The the project we investigate the role of the Wnt-pathway in the haematopoietic system and its effects on cell fate decision.
Institute of Neurology (Edinger-Institute) University Hospital, Goethe University Frankfurt Heinrich-Hoffmann-Str. 7 Building 89, 4.Floor, R402 60528 Frankfurt/Main, Germany