Meibergdreef 9 1105 AZ Amsterdam

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The role of integrins in small artery remodeling.

 

Description

 

Integrin adhesion molecules are main mediators of cell-matrix adhesion and matrix-dependent signaling. Integrins mediate tensile stress from and to the extracellular matrix, and respond to and modulate signaling pathways relevant to vascular biology, including Akt, Notch, and VEGFR2.

 

Hypothesis. Endothelial cell and vessel wall integrins are essential regulator and mediators of vascular remodeling. They contribute to sensing of shear stress and wall tension, and they regulate and mediate cell-signaling events relevant for wall remodeling. They form critical points of convergence in many cascades of events associated with vascular remodeling.

 

Objectives. We will build on our recent observations that MAGI1 and Cx31 modulate integrin signaling and cell adhesion and on the observation by partner 2, that laminins, in particular the α4 chain, participate in vascular plasticity and remodeling. The main objective is to identify pathways being modulated by MAGI1, integrin ligation (in particular to laminins) or Cx31.

 

Training. The ESR will be trained in a range of molecular techniques, applied to both in vitro and in vivo models. These include:

1. Gene over-expression or silencing (shRNA) to monitor the effect on the response to increased shear (flow chamber) and mechanical (elastic substrate) stresses.

2: Proteomics (protein expression and phosphorylation, with partner KC) and transcriptomics (target gene expression by RT-PCR).

3. Atomic force microscopy, cell migration and proliferation (time lapse imaging).

4. Perfused vessels ex vivo and in vivo using models of inward remodeling (in collaboration with partners WWU, LMU, and UKH).

Publications

n/a

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Ph.D student / post-doc

Begoña Alday Parejo

 

Principal Investigator

Prof. Curzio Rüegg