Sarah De Val
- BHF Senior Fellow
- Ludwig Adjunct Scientist
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.
Regulation within the vascular endothelium is heavily context-dependent and many common pathways are involved in multiple different processes. To delineate the regulatory frameworks controlling vessel growth in this complex system, my lab studies gene enhancers (cis-regulatory elements) active in different types of endothelium. Enhancers are densely clustered groups of transcription factor binding motifs, and are the principal regulators of spatial and temporal patterns of gene transcription. Analysis of enhancers can identify the precise transcription factors required to achieve specific patterns of gene expression within discrete endothelial sub-populations. Once these factors have been defined, transgenic animal models expressing reporter genes under the control of these enhancers become powerful tools in their own right. These animals can be used to study different transcriptional pathways at any stage of development or disease, and to determine the upstream signalling cascades which act via these factors.
This work involves a variety of model systems including transgenic mouse and zebrafish, tissue culture and in silico analysis.
Venous identity requires BMP signalling through ALK3.
Neal A. et al, (2019), Nature communications, 10
MEF2 transcription factors are key regulators of sprouting angiogenesis
Sacilotto N. et al, (2016), Genes & Development, 30, 2297 - 2309
regulation reveals a combinatorial role for Sox and Notch in arterial development
Sacilotto N. et al, (2013), Proceedings of the National Academy of Sciences, 110, 11893 - 11898
ETS factors are required but not sufficient for specific patterns of enhancer activity in different endothelial subtypes
Neal A. et al, (2021), Developmental Biology, 473, 1 - 14
Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Response.
Zhang P. et al, (2021), Cancer research, 81, 1667 - 1680