Using the Zebrafish Model to Understand Vascular Biology and Human Stroke

Dr. Sarah Childs,  Associate Professor, Biochemistry & Molecular Biology, AHFMR Senior Scholar; Canada Research Chair (Tier II – Genetics/Angiogenesis)

We use the zebrafish model to understand human genetic vascular disease. Pathological blood vessel growth accompanies many human diseases. We use the transparency and rapid growth of zebrafish to visualize blood vessel growth and remodelling in real time. In humans, loss of Rasa1 leads to Capillary Malformations-Arteriovenous Malformations syndrome, a syndrome with tangled capillary malformations on the skin, and hidden arteriovenous malformations in the brain and other organs. We used CRISPR mutagenesis to target Rasa1 in the zebrafish model, and trace arteriovenous malformation development in real time. We also note defects in the migration of endothelial cells to form capillaries, potentially explaining capillary malformations in humans. We also study vascular stability and stroke. Genome Wide Association studies link polymorphisms near the FoxF2 transcription factor locus with ischemic stroke in the general population. By genetic targeting of FoxF2 we show that this transcription factor is expressed in vascular mural cells that support the fragile endothelial lining, and are required for vascular stability. 



About the Speaker...

The Childs lab is interested in the development of the vascular system, neural crest and eye, and in determining the genes that drive normal development as well as the mechanisms by which mutations in key genes result in defects using the zebrafish model. Dr. Childs undertook her PhD at the University of Toronto, before moving to the BC Cancer Research Centre and Harvard Medical School for postdoctoral work. In Boston, she joined the rapidly growing field of zebrafish research, taking part in some of the first genetic screens for defects in cardiovascular development.

Since moving to the University of Calgary in 2001, she has been instrumental in discovering signals for normal vascular patterning, angiogenic growth  and vascular stabilization by studying the genetics of endothelial and smooth muscle cells. .

Each of these projects uses the zebrafish as a genetic model to probe pathways, starting from a gene essential for normal development and connecting interacting genes to understand cellular mechanisms. The lab also has a strong interest in connecting basic research in the zebrafish model to human genetic disease by using the zebrafish to model rare human diseases.

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