Amanda Kennedy

Supervisor: Dr Anthony Davenport

Title: Characterisation and functional studies of the GPR1 transmitter system

Abstract: G-Protein coupled receptors (GPCRs) are important drug targets in many diseases, including cardiovascular disease. Recently discovered orphan GPCRs with unknown functions, like G-protein coupled receptor 1 (GPR1), could also prove to be successful drug targets. The BRIGHT study identified GPR1 as a candidate gene that corresponded to a region of interest in the genome-wide mapping of human loci for essential hypertension. In addition, the GPR1 gene was found to be regulated during a pivotal stage in the onset and progression of atherosclerosis. Chemerin is known to activate the CMKLR1 receptor; and has been proposed as the ligand for GPR1. Chemerin has also been implicated in the development of atherosclerosis.  

This research seeks to characterise the GPR1 signaling pathway in the cardiovascular system; distinguish the effects mediated by the two receptors through selective agonists and antagonists, and explore the role of GPR1 in atherosclerosis.

Posters:

• British Pharmacological Society (BPS) Winter Meeting 2015, London: ‘Chemerin contracts human vessels via CMKLR1’
• Department of Medicine, University of Cambridge, Research Day 2015: ‘Characterisation of the chemerin axis in the human vasculature’
• Early Careers Cardiovascular Research Event, Cambridge 2015: ‘‘Characterisation of the chemerin axis in the human vasculature’
• American Heart Association Hypertension Scientific Sessions 2015, Washington DC: ‘Characterisation of the chemerin axis in the human vasculature’
• Physiology 2015, Cardiff: ‘Characterisation of the chemerin signalling pathway: CCX832 is a selective antagonist for the human CMKLR1 receptors.’
• BPS Focused Meeting: Exploiting the new pharmacology and application to drug discovery 2015, Edinburgh: ‘Characterisation of the chemerin signalling pathway: CCX832 is a selective antagonist for the human CMKLR1 receptors.’
• BHF Centre of Research Excellence Day 2015, Cambridge: ‘Chemerin: more than just a chemokine’
• Department of Medicine, University of Cambridge, Research Day 2014: ‘Chemerin: more than just a chemokine’.
• British Hypertension 2014, Edinburgh: ‘Chemerin: more than just a chemokine’.
• 4 year BHF PhD Student Conference 2014, Manchester: ‘Chemerin: more than just a chemokine’.
• Department of Medicine, University of Cambridge, Research Day 2013: ‘The GPR1/Chemerin system in the human vasculature’
• eSCAMPS Student Conference, 2013, Cambridge: ‘The GPR1/Chemerin system in the human vasculature’
• British Atherosclerosis Society and British Society for Cardiovascular Research Joint Spring Meeting, 2013, London: ‘Forkhead transcription factor FOXO3a potently induces smooth muscle cell apoptosis and promotes extracellular matrix degradation through activation of matrix metalloproteinases’

Talks:

• British Pharmacological Society Winter Meeting 2014 – Oral Presentation ‘Expression of chemerin receptors GPR1 and CMKLR1 in human vascular tissue and evidence for chemerin as a novel vasoconstrictor.’

Prizes:

• 2015 British Pharmacological Society Bain Memorial Bursary Fund Award
• 2015 Cambridge Cardiovascular Early Careers Event Poster Prize
• 2015 St Catharine’s College Graduate Travel and Research Fund Award
• 2015 British Pharmacological Society Bain Memorial Bursary Fund Award
• 2015 British Heart Foundation Travel Award
• 2015 The Physiological Society Travel Award
• BPS Focused Meeting: Exploiting the new pharmacology and application to drug discovery Poster Prize
• 2015 St Catharine’s College Graduate Travel and Research Fund Award
• 2015 Abcam Grant recipient for 4 year BHF student conference
• 2014 St Catharine’s College Graduate Travel and Research Fund Award
• 2014 British Pharmacological Society Bain Memorial Bursary Fund Award
• 2014 St Catharine’s College Graduate Travel and Research Fund Grant Recipient for Student travel to 4 year BHF Student conference in Manchester
• 2013 St Catharine’s College Graduate Travel and Research Fund Award
• 2013 Honourable mention University of Cambridge, Department of Medicine Research Day, Poster competition
• 2013 BAS Student Travel Bursary

References:

Kennedy AJ, Kuc RE, Maguire JJ, Davenport AP: Characterisation of the chemerin axis in the human vasculature. Hypertension. 2015; 66: AP624

Kennedy AJ, Kuc R, Maguire JJ, Davenport AP: Expression of chemerin receptors GPR1 and CMKLR1 in human vascular tissues and evidence for chemerin as a novel vasoconstrictor. British Pharmacological Society. 2014 E-journal publication

Kennedy A, Littlewood T, Bennett M, Yu H: Forkhead transcription factor FOXO3a potently induces smooth muscle cell apoptosis and promotes extracellular matrix degradation through activation of matrix metalloproteinases. Heart 2013; 99: A94-A95.