My work is based on both the Paul Riley and Roger Patient laboratories to screen a library of small compounds for increasing endogenous cardiovascular progenitor cell activation to ultimately invoke optimal repair of the heart following myocardial infarction. The focus is mainly on two resident cardiovascular cell populations:
i) The outer layer of cells lining the heart muscle, called the epicardium, as an essential lineage during development that becomes partially reactivated following cardiac injury. The first phase of my work involves screening thousands of compounds in vitro using assays designed to monitor epicardial cell shape changes indicative of epithelial-mesenchyme transition (EMT, a surrogate for epicardial cell activation). The second phase involves validation of hits in secondary screens and in vivo testing of compounds in animal models (zebrafish, medaka and mouse) of acute cardiac injury.
ii) The lymphatic vessels of the heart and specifically lymphatic endothelial cells which might be invoked to undergo sprouting (lymphangiogenesis) to improve tissue fluid and immune cell clearance following cardiac injury and thus establish a more conducive environment for resident cell therapies. The first phase of my work involves establishing assays designed to monitor lymphatic vessel sprouting and/or immune cell (macrophage) uptake in co-cultures. The second phase involves miniaturizing the assays and application to screening thousands of compounds in vitro for inducers of lymphangiogenesis and improved macrophage uptake, followed by secondary screens and in vivo testing of compounds in animal models (zebrafish, medaka and mouse) of acute cardiac injury.