Research Aims & Objectives
Regulation of blood and lymphatic vessel development
We seek to:
- understand how blood vessels grow, differentiate and regress during development, with a particular emphasis on coronary vasculature
- study how developmental regulatory programs respond in the adult after injury and disease, or during tissue regeneration
- investigate mechanisms to perturbate vascular regulatory pathways in order to manipulate vascular growth where needed
Details of research interests
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 for repair after injury, during tissue regrowth, 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 in different types of blood and lymphatic endothelial cells. 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).
Both zebrafish and mammalian transgenic models are used. This allows us to take advantage of the ease of visualisation, genome engineering, knock-down and transgenesis in zebrafish embryos, while ensuring conservation to mammalian systems. It also provides a more human-relevant model for cardiovascular studies. In particular, this permits us to study the development of coronary vessels both during physiological growth and after ischemic injury.
Sarah J. De Val
- Dr Susann Bruche
- Dr Lucija Fleisinger
- Dr Svanhild Nornes
- Dr Sophie Payne
- Dr Helena Rodriguez Caro
- Dr Dorota Szumska
Collaborators - Oxford:
Collaborators - External:
- Mat Francois, University of Sydney
- Mukesh Jain, Case Western Reserve University, Ohio, US
- Martin Schwartz, Yale University, New Haven, US
- British Heart Foundation
- Fondation Leducq
- Medical Research Council
The De Val lab actively engages in public engagement activities in our local area and beyond. We explain and present our work, and the scientific principles behind it, at local events (including at our neighborhood farmers market and our building’s Open Doors event) and at major festivals including the Cheltenham and Oxford annual science festivals. We also participate in programs to engage local school children in our research, including regularly hosting sixth form students for work experience (both arranged directly via local secondary schools and via the In2scienceUK program designed to empower young people from disadvantaged backgrounds to achieve their potential).