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
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
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- 30 July 2018Q&A with Anthony Shepherd, IMB Senior IT Manager (Operations)
- 23 July 2018Australia has an incredible diversity of native spiders, including the potentially lethal funnel-web, the ubiquitous huntsman, and the charming peacock spider.
- 23 July 2018Bites or stings from venomous animals or insects can be dangerous; they lead to numerous fatalities globally each year despite the development of antivenoms that can neutralise many of their worst effects.
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