Sarah De Val
BHF Senior Fellow
- Ludwig Adjunct Scientist
My research aims to develop novel strategies to modulate vessel growth. This is directly relevant to the ischemic heart, where neovascular growth is insufficient and current strategies to improve this have failed.
I have worked on different aspects of gene regulation throughout my career. In particular, my research focuses on the transcriptional pathways which regulate the dynamic gene expression patterns required for correct formation and function of the mammalian vascular system. During my post-doctoral research, I combined the analysis of gene enhancers (densely clustered groups of transcription factor binding motifs which regulate spatial and temporal patterns of gene transcription) with in vivo gene depletion models to describe a transcriptional pathway that regulates endothelial cell (EC) specification (De Val et al., Cell, 2008). As an independent researcher, my lab is focused on understanding the regulatory mechanisms controlling angiogenesis (new EC growth from existing vessels), vascular differentiation and heterogeneity.
We take an enhancer-centric approach, which focuses on identifying different types of EC enhancers and elucidating the transcriptional and signaling components that regulate them. This is combined with direct in vivo analysis to determine the role of each of these factors in vascular specification, growth and homeostasis. This approach has been used by my laboratory to delineate a SOXF/NOTCH regulatory pathway controlling arterial endothelial cell identity (Sacilotto et al., PNAS 2013; Becker et al., ATVB 2016; Chiang, et al., Development 2017) and a VEGFA-MEF2 pathway controlling angiogenic EC behaviour (Sacilotto et al., Genes Dev 2016), and our recent work is now focused on vein and lymphatic identity.
We use both zebrafish and mouse models. This allows us to take advantage of the ease of visualisation and speed of genome engineering, knock-down and transgenesis in zebrafish embryos, while ensuring conservation to mammalian systems and providing a human-relevant model for studying pathological conditions. We are also able to use the transgenic mouse and zebrafish lines generated during enhancer analysis as powerful tools to study the behaviour of different vascular pathways in pathological conditions.
Our work has been funded by grants and fellowships from the British Heart Foundation, the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Oak Foundation and the Ludwig Institute for Cancer Research.
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
Analysis of Dll4 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