|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.
ETS factors are required but not sufficient for specific patterns of enhancer activity in different endothelial subtypes.
Neal A. et al, (2021), Dev Biol
Coronary vessel formation in development and disease: mechanisms and insights for therapy.
Lupu I-E. et al, (2020), Nat Rev Cardiol, 17, 790 - 806
Regulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart
PAYNE S. et al, (2019), Nature Communications
Venous Identity Requires BMP Signalling Through ALK3
NEAL A. et al, (2018), Nature Communications
Endothelial-Specific Cre Mouse Models: Is Your Cre CREdibile?
DE VAL SJ. et al, (2018), Arteriosclerosis, Thrombosis, and Vascular Biology