Determining the key regulators of endocardial to coronary endothelial cell transition in development and disease

The endocardium acts as a substantial source of the coronary vascular endothelium during murine heart development which I have revealed is conserved in the human foetal heart. However, the regulation of endocardium to endothelium transition remains unknown.

Improved understanding of the mechanisms underpinning this transition is likely to reveal new therapeutic targets to promote revascularisation following myocardial infarction.

In this project, I will apply the latest single cell omics technologies to a murine endocardial-lineage tracing model combined with my refined in-house human pluripotent stem cell-derived endocardial cell (hPSC-ECC) culture platform to map the conserved transcriptional and epigenomic landscape throughout the formation of the coronary endothelium.

Systematic identification of factors promoting the transition to coronary endothelial cells will be achieved by genome-wide CRISPR gain of function screening.

Combining murine and human models will collectively enable identification of the key conserved regulators which I will subsequently validate and functionally test for their ability to promote endocardial angiogenesis in the ischaemic adult heart.