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Dr. James Spiers

Associate Professor (Pharmacology & Therapeutics)
Associate Professor (Molecular Medicine Ireland)
 (3531896) 2146
TRINITY CENTRE, S J H
      
Profile Photo

Dr. James Spiers

Associate Professor (Pharmacology & Therapeutics)
TRINITY CENTRE, S J H

 Paul.Spiers@tcd.ie

 3531896 2146

Associate Professor (Molecular Medicine Ireland)

 (3531896) 2146


  CALCIUM   Cardiac physiology   Cardiovascular and molecular pharmacology   Cardiovascular disease, pharmacology   CLINICAL-TRIALS   CONVERTING ENZYME   CYCLOSPORINE-A   CYP3A4   Cytokines, Nitric Oxide   DEPRESSION   DIGOXIN   ENDOTHELIN   ENDOTHELIN RECEPTOR   ENDOTHELIN-1   ENDOTOXIN   ETA-RECEPTOR   FAILURE   FLOW CYTOMETRY   Heart Failure and transplantation   HIV PROTEASE INHIBITORS   Human genetics   HUMAN HEART   HYPERICUM-PERFORATUM   Intra and intercellular signalling   INVITRO   MDR1   Membrane and protein trafficking   MESSENGER-RNA   NITRIC OXIDE   NUCLEAR RECEPTOR   Pathophysiology   PEPTIDES   P-GLYCOPROTEIN   PP2A   PREGNANE-X RECEPTOR   Protein Phosphatase 2A   RELEASE   REMODELING   RITONAVIR   SEPSIS   SMOOTH-MUSCLE CELLS   ST JOHN'S WORT   Vascular Biology, Thrombosis
Project Title
 Cardiovascular Remodeling in Heart Failure
From
2002
To
2004
Summary
Assessment of cardiovascular remodelling due to physiological ageing in contrast to pathophysiological disease, particularly heart failure. This recent work has resulted in the identification of accelerated ageing processes in disease and further identified specific signalling pathways associated with hypertension and failure. Key findings reported from this work include: . endothelin receptors are responsible for altered matrix metalloproteinase activity in chronic hypertension but not acute hypertension. Br J Pharmacol 2003, 138, Suppl S, 56P . â-adrenoceptor blockade exhibits a novel anti-remodelling effect in patients with heart failure through attenuation of matrix metalloproteinase activity. Br J Clin Pharmacol. 2003, 55, 426-427 . raised MMP levels prior to reduced cardiac function in viral myocarditis, may provide a useful marker of deteriorating function and have a role in the pathogenesis of myocardial lesion. Chin Med J. 2004; 117, 1195-1199 These findings have been examined in an animal model of hypertension and heart failure, and also in patients. I have set up all the methodologies necessary for these investigations in the department including zymography and investigations of specific target protein expression. The later study was set up as an international collaboration in order to avail of expertise and ready access to an animal model of viral myocarditis. Successful outcome is noted in publication of work.
Funding Agency
Royal City of Dublin Hospital Trust
Project Title
 Novel Mechanism Associated with the Development of Heart Failure
From
2003
To
2005
Summary
Questions relating to molecular mechanisms associated with the development of heart failure are currently being addressed through 3 collaborative programmes: (i) Professor Zhao, China; (ii) Professor Wang, China, and (ii) Professor Krainias, U.S.A. We are utilising already established cell systems set up by these teams, in addition to valuable resources, including constructs, to address: . the promoter region of MMP-9 and the responsiveness to adrenergic stimulation through specific subtypes, temporal dynamics and location of involvement . HSP20 polymorphisms: we have successfully sequenced the gene and are currently looking at polymorphisms in exon 1 of the gene in heart failure patients. Results from this work have identified eight polymorphisms to date. . functional responsiveness of HSP20, through introduction of the gene into viral vectors which are then used to transfect adult cardiomyocytes. It is early to identify the significance of this work, but from results to date it would appear that we have identified a cardioprotective role of HSP20, and it is likely that the presence of polymorphisms will reflect poor outcome. This work is particularly exciting and will lead to a number of publications, in addition to forming the basis of future grant applications and investigations.
Funding Agency
HEA Cycle III
Project Title
 Immunomodulatory-matrix metalloproteinase (MMP) inhibition with tetracyclines in obesity, diabetes and asymptomatic left ventricular diastolic dysfunction: impact on MMP-9 levels and cardiovascular structure and function
From
To
Summary
Funding Agency
Health Research Board

Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
Details Date From Date To
British Pharmacological Society 1988 present
Scottish Cardiovascular Society 1992 present
Irish Association of Pharmacologists 1990 present
European Society for Cardiology 2003 2014
International Society for Heart Research 1997 2014
British Society for Cardiovascular Research 1997 2014
American Heart Association 2005 2012
Chris Watson, J Paul Spiers, Max Waterstone, Joseph Gallagher, Cristin Ryan, John Gilmer, Kenneth McDonald, Mark T Ledwidge, Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in European patients with diabetes: a report from the STOP-HF follow-up programme, BMC Cardiovascular Disorders, 21, 2021, p87 , Journal Article, PUBLISHED
Sotirakos, S. Wheen, P. Spiers, J. Armstrong, R., New pharmacotherapy for heart failure with reduced ejection fraction, Expert Reviews in Cardiovascular Therapy, 18, 2020, p405 - 414, Journal Article, PUBLISHED
Holmes, D. Corr, M. Thomas, G. Harbinson, M. Campbell, M. Spiers, J.P. Bell, D., Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension, Peptides, 126, 2020, p170267 , Journal Article, PUBLISHED
Mahmud, A Zhou, S Yasmin, Y Spiers, JP Feely, J Silke, B, Haplotype of receptor for advanced glycation end products is associated with arterial stiffness in essential hypertension, European Heart Journal, 41, 2020, ppehaa946. 2705 , Meeting Abstract, PUBLISHED
MAHMUD, A., MCNULTY, M., MCGOVERN, E., SPIERS, J., KAVANAGH, P., TOLAN, M., YOUNG, V., FEELY, J. & SILKE, B., Arterial stiffness is associated with elastin fragmentation and medial collagen content in the human aorta, European Heart Journal, 41, 2020, ppehaa946. 2706 , Meeting Abstract, PUBLISHED
KONIECZNA, S., OHLMEYER, M. & SPIERS, J. P., Role of protein phosphatase 2a inhibition in modulation of claudin-5 and ve-cadherin in human brain microvascular endothelial cells., Heart, 2020, Meeting Abstract, PUBLISHED
I.S. Elgenaidi, J.P. Spiers, Hypoxia Modulates the PP2A system in Human Cardiovascular Cell Lines: HIF-1alpha Dependent and Independent Regulation of PP2A in Aortic Smooth Muscle Cells and Ventricular Cardiomyocytes, British Journal of Pharmacology, 176, (11), 2019, p1745 - 1763, Journal Article, PUBLISHED  DOI
I.S. Elgenaidi, J.P. Spiers, Regulation of the Phosphoprotein Phosphatase 2A System and its Modulation during Oxidative Stress: A Potential Therapeutic Target?, Pharmacology and Therapeutics, 2019, p68 - 89, Journal Article, PUBLISHED  DOI
Elgenaidi, I.S. and Spiers, J.P., 5†HIF-1alpha dependent and independent regulation of PP2A in human aortic smooth muscle cells under hypoxia , Heart, Scottish Cardiovascular Forum, Dublin, 104, Heart, 2018, Meeting Abstract, PUBLISHED  DOI
MAHMUD, A., ROUF, A., SPIERS, J. P., ALJIZEERI, A., FEELY, J. & JERRARD-DUNNE,, Relationship between smoking and smoking cessation with vasculature inflammation and arterial stiffness, ournal of the American College of Cardiology, 71, 2018, ppA2114-A211 , Meeting Abstract, PUBLISHED
  

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Award Date
Fellow of the British Pharmacological Society 1st November 2021
Provost's Teaching Award 2008
MA from Trinity College Dublin 2003
Wellcome Trust Travelling Fellowship 2002
Harold McCauley Scholarship for Cardiovascular Research 1995
Samuel Haslett Brown Scholarship 1990
Pathophysiological mechanisms of cardiovascular disease processes: activation of compensatory/ decompensatory mechanisms. Cellular and molecular investigations of cardioactive substances in normal and diseased myocardium: changes in myocyte function in response to overexpression of neurohormones and peptides; long-term cellular changes, including hypertrophy and altered gene expression; extracellular and cytoskeleton changes - ventricular remodelling. Roles of endothelin, nitric oxide, cytokines and heat shock proteins in heart failure and septic shock: factors implicated in altered myocardial responses, including receptor and post-receptor mechanisms of action; mechanical, biochemical, molecular and electrophysiological effects.