Our laboratory uses both transgenic zebrafish and transgenic mice to investigate the transcriptional regulation of genes in the vasculature. In this figures, a vascular-specific enhancer is driving GFP expression (greeen) in transgenic zebrafish, and LacZ expression (blue) in transgenic mice. Histological analysis of transient sections demonstrates the endothelial cell (ec) specificity of expression. |
Dr Sarah De Val
University Research Lecturer
The goal of my laboratory is to understand how blood vessels grow, differentiate and regress through studying the transcriptional regulation of vascular genes.
The vascular system is a highly branched network of endothelial cell-lined tubes that transports blood, metabolites and waste products throughout the body. In addition to being essential for embryonic development, the formation of new blood vessels is required after injury, during tissue regrowth and repair, and for the growth and spread of solid tumours. However, our ability to manipulate vessel growth for therapeutic aims is hampered by a poor understanding of the mechanisms regulating vessel growth in both physiological and pathological contexts.
To study vessel regulation, my laboratory primarily focuses on the identification, characterization and delineation of enhancers (cis-regulatory elements) directing gene expression within the vasculature. Enhancers are densely clustered groups of transcription factor binding motifs and are the principal regulators of spatio-temporal patterns of gene transcription. Analysis of the proteins that activate and repress different enhancers is combined with genetic studies to accurately position these factors within complex signalling networks. We are using this approach to understand what makes blood vessels molecularly different from each other, to determine the signalling cascades involved at different stages of vessel growth, and to study these processes during tumour formation and growth.
This work involves a variety of model systems including transgenic mouse and zebrafish, tissue culture and in silico analysis.
Recent publications
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A catalogue of verified and characterized arterial enhancers for key arterial identity genes
Preprint
Nornes S. et al, (2024)
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Transcriptional regulators of arteriovenous identity in the developing mammalian embryo
Journal article
McCracken I. et al, (2023), Current Opinion in Physiology
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Krüppel-Like Factors Orchestrate Endothelial Gene Expression Through Redundant and Non-Redundant Enhancer Networks.
Journal article
Sweet DR. et al, (2023), J Am Heart Assoc, 12
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Analysis of Placental Arteriovenous Formation Reveals New Insights Into Embryos With Congenital Heart Defects
Journal article
KALISCH-SMITH J. et al, (2022), Frontiers in Genetics
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Regulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart
Journal article
PAYNE S. et al, (2019), Nature Communications