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Dr Janet Maguire

Dr Janet Maguire

Senior Research Associate


Office Phone: 01223 762579

Research themes

Experimental Medicine:

Research Interests

G protein-coupled receptors (GPCRs) are expressed on the surface of cells and found throughout the body. This class of proteins has clinical relevance as they are the target for about a third of currently prescribed medicines.  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 cardiovascular diseases such as pulmonary arterial hypertension.  Focus is particularly on elucidating whether biased apelin ligands may have an advantage over current therapies.

Keywords

G-protein coupled receptors ; Endothelin ; Apelin ; pulmonary arterial hypertension

Collaborators

Key Publications

  1. Yang P, Read C, Kuc RE, Nyimanu D, Williams TL, Crosby A, Buonincontri G, Southwood  M, Sawiak  SJ, Glen RC, Morrell NW, Davenport AP, Maguire JJ. A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension. Br J Pharmacol 2019, 176(9):1206-1221.
  2. Read C, Yang P, Kuc RE, Nyimanu D, Williams TL, Glen RC, Holt LJ, Arulanantham H, Smart A, Davenport AP, Maguire JJ. Apelin peptides linked to anti-serum albumin domain antibodies retain affinity in vitro and are efficacious receptor agonists in vivo.  Basic Clin. Pharmacol. Toxicol. 2019;1–8.
  3. Davenport AP, Kuc RE, Southan C, Maguire JJ. New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine.  Physiol Res. 2018;67(Suppl 1):S37-S54.
  4. 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.  Front Neurosci. 2017;11: doi: 10.3389/fnins.2017.00092. eCollection.
  5. Yang P, Read C, Kuc RE, Buonincontri G, Southwood S, 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.  Circ. 2017;135(12):1160-1173.
  6. Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ. Endothelin. Pharmacol Rev. 2016;68:357-418.
  7. Read C, Fitzpatrick CM, Yang P, Kuc RE, Maguire JJ, Glen RC, Foster RE, Davenport AP.  Cardiac action of the first G protein biased small molecule apelin agonist. Biochem Pharmacol. 2016;116:63-72.
  8. Maguire JJ.  Evidence for biased agonists and antagonists at the endothelin receptors. Life Sci. 2016;159:30-33.
  9. Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP.  Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist.  Hypertension 2015;65:834-840.

 

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