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Robyn Macrae

Robyn Macrae

BHF 4-Year Programme PhD Student


Research Interests

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.  

Keywords

G-protein coupled receptors ; Ca2+signalling ; ES (embryonic stem cells) ; Apelin ; GPCR ; pulmonary arterial hypertension ; CRISPR-Cas9 ; stem cells ; drug discovery ; cardiovascular disease

Key Publications

Publications:

Read, C., Nyimanu, D., Williams, T.L., Huggins, D.J., Sulentic, P., Macrae, R.G.C., Yang, P., Glen, R.C., Maguire, J.J. and Davenport, A.P. (2019) International Union of Basic and Clinical Pharmacology. Structure and pharmacology of the apelin receptor with a recommendation that Elabela/Toddler is a second endogenous peptide ligand. Pharmacological Reviews 71(4): 467-502.

Davenport AP, Kleinz M, Lloyd Williams T, Macrae R, Maguire JJ, Nyimanu D, Yang P. Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE. 2019; 2019(4). Available from: https://doi.org/10.2218/gtopdb/F7/2019.4.

Oral Presentations:

The British Pharmacological Society Pharmacology 2019 Meeting: First application of short hairpin RNA inducible knockdown system to a GPCR to pharmacologically characterise the role of the apelin receptor in hESC derived beating cardiomyocytes.

Posters:

BSCR Autumn Meeting 2019: Generation of a novel inducible knockdown system to characterise the role of the apelin receptor in human embryonic stem cell derived cardiomyocytes. (Runner-up Prize)

The Physiological Society, Biochemical Society and British Pharmacological Society Life Sciences 2019: Post-Translational Modifications and Cell Signalling Meeting, Nottingham: Characterisation of the apelin receptor protein from beating human embryonic stem cell derived cardiomyocytes.

British Pharmacological Society Cell Signalling Meeting 2018: Characterising the apelin/Elabela signalling pathway in human embryonic stem cell derived cardiomyocytes, endothelial and smooth muscle cells.