During a heart attack, restricted coronary blood flow causes the death of heart muscle cells. One way to help the heart recover is by creating new blood vessels. Restoring blood flow to vulnerable heart muscle cells may limit ongoing cell death and prevent progression to heart failure.
This project aims to uncover signals that trigger the process of new blood vessel formation, to identify new therapeutic targets for repairing the injured heart.
Target discoveryIn-depth
Although survival rates after myocardial infarction (MI) have improved, permanent loss of heart muscle cells often results in progressive heart failure. Restoring blood supply through angiogenesis (the growth of new blood vessels) could protect vulnerable heart muscle cells, but clinical trials for cardiac vessel growth have shown limited success. Unlike other organs, the heart’s blood vessel lining has poor capacity to regenerate under stress.
Preliminary studies suggest that some vessel growth occurs naturally in the adult heart after MI, indicating an intrinsic potential that could be enhanced. This project combines lineage-tracing models with single-cell and spatial transcriptomics to uncover the origin and molecular profile of new coronary endothelial cells during cardiomyocyte proliferation.
Candidate factors identified in vivo will be tested in human iPSC-based models of coronary vessel formation for functional validation. Promising targets will then be evaluated in model systems using gene therapy approaches. The goal is to reveal mechanisms and therapeutic targets that drive cardiac neovascularisation, paving the way for regenerative treatments for MI patients.
Partners
This studentship project is delivered in partnership with the Oxford-MRC Doctoral Training Partnership.