Senior Research Associate, University of Cambridge

Fellow of Queens’ College, University of Cambridge.

Email: jjm1003@medschl.cam.ac.uk

Tel: 01223 762579

Research Description

My research explores the pharmacology of G protein-coupled receptors (GPCRs) that are expressed in the human cardiovascular system.  The clinical importance of this class of proteins is evident from the number of drugs that have GPCRs as their molecular target.  However, to date only a small number of the GPCRs predicted to exist in the human genome have been exploited therapeutically.  My aim is to understand the role of recently discovered receptor proteins in normal cardiovascular physiology and how alterations in receptor expression and function may contribute to disease progression.  I have a particular interest in the emerging pharmacological paradigm of biased signalling and how the design of biased ligands may be an important mechanism by which target selectivity and improved efficacy may be built into novel peptides and small molecules. In collaboration with other group members, colleagues within the wider Clinical School cardiovascular network and the Department of Chemistry the group is currently investigating the role of GPCRs (specifically endothelin and apelin receptors) in pulmonary arterial hypertension and related cardiovascular diseases.  Focus is particularly on elucidating whether biased apelin agonists may have an advantage over current therapies.

Recent Publications

• Yang P, Kuc RE, Brame AL, Dyson A, Singer M, Glen RC, Cheriyan J, Wilkinson IB, Davenport AP, Maguire JJ.  [Pyr¹]apelin-13_(1–12) is a biologically active ACE2 metabolite of the endogenous cardiovascular peptide [Pyr¹]apelin-13.  Frontiers Neurosci. 2017;11:article 92.
•  Yang P, Read C, Kuc RE, Buonincontri G, Southwood M, Torella R, Upton PD, Crosby A, Sawiak SJ, Carpenter TA, Glen RC, Morrell NW, Maguire JJ, Davenport AP. Elabela/Toddler is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of its Expression in Pulmonary Arterial Hypertension. Circulation. 2017 [Epub ahead of print] PMID: 28137936.
•  Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ. Endothelin. Pharm Rev. 2016;68:357-418.
•  Maguire JJ. Evidence for biased agonists and antagonists at the endothelin receptors. Life Sci. 2016;159:30-33.
•  Kennedy AJ, Yang P, Read C, Kuc RE, Yang L, Taylor EJ, Taylor CW, Maguire JJ, Davenport AP. Chemerin elicits potent constrictor actions via chemokine-like receptor 1 (CMKLR1), not G-protein coupled receptor 1 (GPR1), in human and rat vasculature. J Am Heart Assoc. 2016;5:e004421.
• Maguire JJ, Jones KL, Kuc RE, Clarke MCH, Bennett MR, Davenport AP.  The CCR5 chemokine receptor mediates vasoconstriction and stimulates intimal hyperplasia in human vessels in vitro_.  Cardiovasc Res (in press).
•  Ling L, Maguire JJ, Davenport AP.  Endothelin-2, the Forgotten Isoform: Emerging Role in the Cardiovascular System, Ovarian Development, Immunology and Cancer.  Br J Pharmacol 2013;168:283-295
• Zheng Y, Humphry M, Maguire JJ, Bennett MR, Clarke MC. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-295.
• Maguire JJ, Kuc RE, Davenport AP. Defining the affinity and receptor sub-type selectivity of four classes of endothelin antagonists in clinically relevant human cardiovascular tissues. Life Sci. 2012;91:681-686.
• Maguire JJ, Kuc RE, Pell VR, Green A, Brown M, Kumar S, Wehrman T, Quinn E, Davenport AP. Comparison of human ETA and ETB receptor signalling via G-protein and β-arrestin pathways. Life Sci. 2012;91:544-549.
• Maguire JJ, Kirby HR, Mead EJ, Kuc RE, d’Anglemont de Tassigny X, Colledge WH, Davenport AP. Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor. PLoS One. 2011;6(11):e27601.
• Jones K, Maguire JJ, Davenport AP.Chemokine receptor CCR5: from AIDS to atherosclerosis. Br J Pharmacol. 2011;162(7):1453-1469
• Kirby HR, Maguire JJ, Colledge WH, Davenport AP.International Union of Basic and Clinical Pharmacology. LXXVII. Kisseptin receptor nomenclature, distribution and function.Pharmacol Rev. 2010;62:565-578.

• Pitkin SL, Maguire JJ,  Kuc RE, Davenport AP.Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br J Pharmacol, 2010;160:1785-1795.
• Kelland NF, Kuc RE, McLean DL, Azfer A, Bagnall AJ, Gray GA, Gulliver-Sloan FH, Maguire JJ, Davenport AP, Kotelevtsev YV, Webb DJ.
  Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1. Can J Physiol Pharmacol. 2010;88:644-651.
• Pitkin SL, Maguire JJ, Colledge WH, Davenport AP.
  International Union of Basic and Clinical Pharmacology. LXXIV. Apelin receptor nomenclature, distribution, pharmacology and function. Pharmacol Rev. 2010;62:331-342.
• Maguire JJ, Kleinz MJ, Pitkin SL, Davenport AP.
  [Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease. Hypertension. 2009;54:598-604.
• Mitchell JD, Maguire JJ, Davenport AP.
  Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. Br J Pharmacol. 2009;158:87-103.
• Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP.
  International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacol Rev. 2009;61:1-8.
• Mitchell JD, Maguire JJ, Kuc RE, Davenport AP.
  Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system.Cardiovasc Res. 2009;81:353-361.
• Maguire JJ, Kuc RE, Kleinz MJ, Davenport AP.
  Immunocytochemical localization of the urotensin-II receptor, UT, to rat and human tissues: relevance to function. Peptides 2008;29:735-742.