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Research Tags

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

Research Projects

Project Title

Cardiovascular Remodeling in Heart Failure

From

2002

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

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

Summary

Funding Agency

Health Research Board

Languages

Language	Skill Reading	Skill Writing	Skill Speaking
English	Fluent	Fluent	Fluent

Memberships

Membership of Professional Institutions, Associations, Societies

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

Publications and other Research Outputs

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., 5â 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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Awards and Honours

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

Research Interests

Description Of Research Interests

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.

Trinity College Dublin, The University of Dublin

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Dr. James Spiers

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

www.tcd.ie/medicine/pharmacology-therapeutic/staff/spiersj/

Research Tags

Research Projects

Languages

Memberships

Membership of Professional Institutions, Associations, Societies

Publications and other Research Outputs

Publications

Awards and Honours

Research Interests

Description Of Research Interests