Aim 1. Targeting resident cell-based repair

1.1 Translating the therapeutic potential of the epicardium

1. Characterisation of the full tissue-resident potential of activated adult epicardial cells (EPDCs)
2. Lead candidate small-molecule-activators of human EPDCs via high throughput phenotypic screening (HTS) and drug discovery
3. Generation of GMP hESC- epicardium (with UKRMP)
4. Development of functional vascularised patches for treatment of impaired LV function post-MI

1.2 Identifying targets to induce neovascularisation, collateral growth and vascular support

1. Identification and functional characterisation of novel cellular sources of new coronary blood and lymphatic vessels post-MI
2. Insight into the gene regulatory networks which determine neovascularisation post-MI and identification of therapeutic regulators of coronary endothelium
3. Small molecule leads for induction of coronary endothelial cells (ECs) from a human ESC-derived endocardium model
4. Identification and evaluation of vascular smooth muscle cell (VSMC) responses post-MI and strategies to augment VSMC proliferation to improve collateral support of new vessel formation from 1) above.