Anne Lagendijk

How to make and maintain a healthy vasculature

Our group aims to understand how our blood vessel network is established during embryonic development and how its function is maintained during life. The development of an aberrant vessel network contributes to a range of cardio-vascular diseases. For example leaky vessels in the brain can cause stroke. In the lab we employ the zebrafish as a model organism since zebrafish embryos are viable ex utero and can be imaged at extremely high resolution which gives us a unique, live, view of vascular development. We make use of existing and novel biosensors in zebrafish to reveal dynamics of adhesion complexes at the cell-cell and cell-matrix interface whilst also examining distribution of tension at these mechanical hubs. By combining these high-end imaging approaches with detailed, innovative molecular genetics approaches, like CRISPR mutagenesis, we explore the fundamental importance of cell-matrix adhesion in vascular biology. We complement this in vivo modelling with analysis of bioengineered human micro-vessels. This adaptable system allows us to detail the impact of physical cues by the environment and by blood flow.

PhD projects include:

- The role of neuropeptides in establishing and maintaining blood vessels in zebrafish and 3D bioengineered human vessels.

- Using CRISPR mutagenesis to uncover novel players that drive a vascular disease that can cause stroke.

- Modelling how the brain vasculature impacts on brain tumors growth and cancer treatment using zebrafish models.

- Profiling changes in tension across wild-type and mutant forms of the adhesion protein VE-cadherin using in vivo live imaging.

- The impact of cell-matrix interactions on vascular growth in zebrafish mutant models.