Vascular heterogeneity

The Blood-Brain-Barrier (BBB) is an important feature of blood vessels to protect the central nervous system (CNS) from toxic or possible harmful substances circulating in the bloodstream. In the circumventricular organs (CVOs) which are small brain areas, located in the midline around the third and fourth ventricle physiologically, there is no vascular BBB established. Although this seems to be contradictory at first, a second look reveals that the CNS has to be in contact with the bloodstream in these specialised brain areas to exchange information between these compartments. Therefore, the CVOs are also called communication points between blood and brain and categorised into sensory and secretory organs according to their physiological function. In the project funded by the German Research Council with in the Research Group FOR2325, we are interested in the molecular mechanisms that regulate the absence of BBB properties within CVO vessels and how modulation of vascular barrier function influences the communication of the brain with the blood, hence with peripheral organs such as the kidney.

DFG FOR2325

Supported by the Deutsche Forschungsgemeinschaft (DFG) research group FOR2325 (2016-2019), “The Neurovascular Interface” LI 911/5-1.

Applications for Master thesis welcome!!

Mobirise

TEAM: Vascular heterogeneity

Klicken Sie auf den Icon oder den Text, um ihn zu bearbeiten oder zu stylen. Klicken Sie auf den blauen Zahnrad-Button in der rechten oberen Ecke, um den Text zu verbergen/anzuzeigen, den Hintergrund des Blocks oder der Karte oder die Anzeit der Icons zu ändern.

Undergraduate students welcome

Regulation of BBB genes in epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common form of refractory epilepsy, characterized by spontaneous recurrent seizures. Functional impairment of the blood-brain barrier (BBB) has been attributed to contribute to the formation and/or progression of the disease. However, a detailed knowledge of the molecular changes at the BBB and the neurovascular unit (NVU) is currently missing. In the project funded by the government of Hesse (LOEWE-CePTER consortium), aims to characterise in detail the effects of MTLE on brain microvessels and endothelial cells. To characterize BBB properties in MTLE, we will isolate microvessel fragments, of morphologically unaffected cortex and epileptic and sclerotic hippocampus tissue of MTLE patients and compare their transcriptome by next generation sequencing (NGS). To examine the role of identified target genes on the BBB, we will overexpress and silence the genes in the expressing cell type of the NVU. We will further test modified cells for their BBB relevant function in co-cultures and by transendothelial electrical resistance (TEER) measurements in vitro.  

LOEWE-CEPTER

Supported by the LOEWE-Centre  CePTER - Center for Personalized Translational Epilepsy Research.

Related articles

Elif Fidan, PhD student

Mobirise

TEAM: The BBB in epilepsy

Klicken Sie auf den Icon oder den Text, um ihn zu bearbeiten oder zu stylen. Klicken Sie auf den blauen Zahnrad-Button in der rechten oberen Ecke, um den Text zu verbergen/anzuzeigen, den Hintergrund des Blocks oder der Karte oder die Anzeit der Icons zu ändern.

Elif fidan

PhD student

Isabela Kiesewetter Zandavalli

Master student

Vascular ageing

Brain endothelial cells (ECs) of the blood-brain barrier (BBB) maintain brain homeostasis via paracellular tight-junctions and specific transporters such as P-glycoprotein. The BBB is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer’s disease (AD): • 80% of cases display cerebral amyloid angiopathy (CAA). • CAA present deposition of amyloid-β (Aβ) at the blood vessels. • The source of perivascular Aβ however is not entirely clear, but endothelial expression of the rate-limiting enzyme for Aβ generation, the beta-secretase 1 (BACE-1), suggests a potentially contribution of vessels to CAA formation and AD pathogenesis (Devraj et al., 2016). Moreover, impairment of the BBB even prior to the onset of symptomatic AD has been shown, pointing out the importance of the vasculature in the brain for AD formation and progression. This project was included in the European Training Network H2020-MSCA-ITN-2015, BtRAIN.

BtRAIN (H2020-MSCA-ITN-2015 675619)

Supported by the HORIZON2020 The Marie Skłodowska-Curie actions, Innovative TRaining Natwork - BtRAIN.

Related articles

Moritz Armbrust, MD
Jennifer Krawietz, master student
Till Janssen, MD student

Veröffentlichen Sie ihre Webseite lokal, via FTP oder in Github Pages. Lassen Sie sich nicht auf nur eine Plattform nur eines Herstellers beschränken.

Mobirise

TEAM: Vascular ageing

Klicken Sie auf den Icon oder den Text, um ihn zu bearbeiten oder zu stylen. Klicken Sie auf den blauen Zahnrad-Button in der rechten oberen Ecke, um den Text zu verbergen/anzuzeigen, den Hintergrund des Blocks oder der Karte oder die Anzeit der Icons zu ändern.

Jennifer Krawietz

Master student

Till Janssen

Cand. med.

Moritz Armbrust

MD

Cell fate decision in the hematopoietic system

Although the Wnt/β-catenin pathway has been intensively studied in the last decades, its role in cell fate decision during haematopoietic differentiation and specifcally, with regard to myeloproliferative neoplasms is incompletely understood. It was reported that „gain of function“ (GOF) of β-catenin in all haematopoietic cells in mice induced anaemia, thrombocytopenia, impaired megakaryocyte (MK)-maturation and faster cell cycle entry of haematopoietic stem cells (HSCs) in vivo (Scheller et al., 2006). In contrast, application of Wnt-ligands on fetal liver cells in vitro increases MK-differentiation and –maturation (Macaulay et al., 2013). In order to understand the role of the Wnt-pathway specifically in MKs, we use transgenic mouse lines and hematopoietic cell lines to investigate whether activation of the Wnt-pathway in specific branches or bifurcation points in the haematopoietic system effects cell fate decision. Particularly, we intend to understand if a constitutively active form of β-catenin favors MK differentiation, providing new insight in megakaryopoiesis and myeloproliferative neoplasms.

DFG-PROJECT

Supported by the Deutsche Forschungsgemeinschaft (DFG), project LI 911/7-1 "The role of Wnt/β-catenin signaling for megakaryocytic cell fate decision".

Related articles

Finn Danker, PhD student

Veröffentlichen Sie ihre Webseite lokal, via FTP oder in Github Pages. Lassen Sie sich nicht auf nur eine Plattform nur eines Herstellers beschränken.

Mobirise

TEAM: Cell fate in hematopoiesis

Klicken Sie auf den Icon oder den Text, um ihn zu bearbeiten oder zu stylen. Klicken Sie auf den blauen Zahnrad-Button in der rechten oberen Ecke, um den Text zu verbergen/anzuzeigen, den Hintergrund des Blocks oder der Karte oder die Anzeit der Icons zu ändern.

Finn Danker

PhD student

Address

Institute of Neurology (Edinger-Institute)
University Hospital, Goethe University Frankfurt
Heinrich-Hoffmann-Str. 7
Building 89, 4.Floor, R402
60528 Frankfurt/Main, Germany

Imprint of the University Clinic Frankfurt
Data Protection Declaration of the University Clinic Frankfurt

Site was designed with Mobirise