Robyn Macrae

Supervisors: Prof Anthony Davenport and Dr Sanjay Sinha

Title: The apelin signalling system is composed of the G-protein coupled apelin receptor and its two endogenous peptide ligands, apelin and Elabela/Toddler (ELA).  Both the apelin receptor and its ligands are expressed throughout the cardiovascular system and are thought to play important roles in cardiovascular development and physiology, acting via inotropic and vasodilatory responses.  Owing to these beneficial effects, it has been proposed that the apelin system could be a therapeutic target in a range of cardiovascular diseases, including pulmonary arterial hypertension (PAH) and heart failure.  However, the molecular mechanisms through which the apelin receptor acts are poorly characterised. Here, a human embryonic stem cell (hESC) based model is utilised to investigate apelin receptor function in cardiomyocyte development, physiology and pathophysiology.   Additionally, genetic engineering technologies have been utilised, which permits tight regulation of apelin receptor expression throughout the differentiation process. This will provide an innovative approach to develop strategies to target the apelin receptor therapeutically in cardiovascular disease, where novel treatments are urgently needed.