Regulation of blood and lymphatic vessel development
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, characterisation 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 in different disease states, and during repair after injury (e.g. after a heart attack).
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), Nat Commun, 10
Venous identity requires BMP signalling through ALK3.
Neal A. et al, (2019), Nat Commun, 10
22 July 2019
A collaborative paper from the De Val and Smart Groups has established multiple regulatory pathways responsible for the formation of blood vessels in the developing heart. In doing so they have identified a crucial pathway that is repressed in the adult heart after injury, which may hold the key to a new and improved strategy for repair.
Sarah De Val set to expand critical research into endothelial cell dysfunction in cardiovascular disease
12 July 2019
Prof Sarah De Val in collaboration with Dr Gillian Douglas from the Radcliffe Department of Medicine has received a grant from the John Fell Fund to support their work investigating the behaviour of different endothelial regulatory pathways during disorders of the cardiovascular system.
7 June 2019
A series of internal talks demonstrated an extensive breadth of research within the Development and Cell Biology Theme that tackles the questions fundamental to understanding evolution, growth, organ formation, the onset of disease and tissue regeneration. DPAG Researchers were also joined by two external speakers presenting their research into age-related angiocrine signals and stem cell strategies for lung development.
Collaborations & Funding
Prof Nicola Smart (Department of Physiology, Anatomy and Genetics, Oxford): Vessel formation in the injured heart.
Dr Gillian Douglas (Ratcliffe Department of Medicine, Oxford): Regulatory pathways active in cardiovascular pathologies.
Prof Adrian Harris (Department of Oncology): Transcriptional networks active during different modes of tumour angiogenesis.
Prof Ralf Adams, Prof Mukesh Jain, Prof Mark Kahn, Prof Martin Schwartz and Prof Michael Potente (Leducq Transatlantic network): The Transcription Factor KLF2 and Cardiovascular Disease
British Heart Foundation (Personal Senior Fellowship; Project Grant; DPhil Studentships)
Medical Research Council (Project Grant)
John Fell Fund (Pilot Grant)
BHF Oxford Centre of Excellence (Pilot Grants)
Join the De Val Lab
Current vacancies for postdoctoral scientists can be found on the Oxford University and DPAG Vacancies web pages. Alternatively, I am always happy to discuss opportunities for suitable applicants to secure fellowship funding.