Cellular mechanisms to maintain a healthy vasculature

Understanding how a heterogenous blood vessel network is established and maintained, providing insights in how we can tailor these different vessel types for therapeutic purposes

 

We are interested in how our blood vessel system is formed during embryonic development and how function of the system is maintained throughout life.

Arteries, veins and capillaries are architecturally extremely heterogeneous. The endothelial cells (ECs), that make up the inner lining of all these vessels types, need to continuously adapt their size, adhesiveness, compliance and ECM composition in order to ensure the right balance between vessel integrity and permeability.

Mechanical cues play a major role in the differentiation and functional adaptation of ECs and aberrant physical cues have been implicated in vascular diseases, like vascular malformations, atherosclerosis and hypertension. Studies in cultured ECs revealed that the adhesion molecule Vascular Endothelial (VE)-cadherin can function as a receptor for force at cell-cell junctions. At the cell-matrix interface, Integrin adhesion molecules perform a similar mechanoreceptor function.

Dr. Lagendijk previously developed a VE-cadherin tension biosensor line in zebrafish. This line reports intra-molecular tension across VE-cadherin live and was initially utilized to identify changes in junctional organization and VE-cadherin tension that occur as arteries mature and revealed molecular pathways that allow for this maturation to happen.

Currently, the lab is continuing on from this work by examining in more detail how force-bearing proteins control mechanical homeostasis of endothelial cells during vascular development, both at the cell-cell and the cell-matrix interface.

In addition, the lab has established disease models for vascular malformations that are known to lead to neurological deficits and stroke. Modelling in zebrafish and 3D engineered human vessels allows us to investigate the initiating mechanisms of these vascular pathologies at unprecedented cellular and subcellular resolution.

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Group leader

Dr Anne Lagendijk

Dr Anne Lagendijk

Group Leader, Cellular mechanisms to maintain a healthy vasculature

Group Leader, Division of Genomics of Development and Disease

  +61 7 334 62105
  a.lagendijk@imb.uq.edu.au
  UQ Researcher Profile

Our approach

We combine the strength of the zebrafish as a genetic model that is extremely suitable for live imaging, with a platform for generating 3D bioengineered human micro-vessels.

These models allow us to uncover the mechanisms that are essential for endothelial cell function in lumenized vessels that are under flow pressure and are exposed to physiologically relevant extracellular cues. In zebrafish we apply technically challenging genetic, transgenic and live-imaging approaches that probe endothelial cell function live, up to level of single cells.

In addition, our recently implemented platform of bioengineered human vasculature complements the zebrafish work and allows us to tune and test parameters that contribute to EC biology, like blood flow and ECM stiffness.

Aims to achieve

Together our work contributes to understanding how a heterogenous blood vessel network is established and maintained and we aim to provide insights in how we can tailor these different vessel types for therapeutic purposes.

Research areas

  • Vascular morphogenesis
  • Mechanobiology
  • Cell Adhesion
  • Vascular disease modelling
  • Brain cancer biology
     

Our team

Group leader

  • Dr Anne Lagendijk

    Senior Research Fellow - GL & Group Leader, Division of Genomics of Development and Disease
    Institute for Molecular Bioscience

Research members

Research excellence

$1.3 billion+ commercial investment attracted to IMB research
1454 international collaborators
 
385 original publications in 2020
 
$28M in research funding last calendar year
 
20%+ of patent families at UQ are derived from IMB research
100% of donations go to the cause
 

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