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James Spiers
Associate Professor, Pharmacology & Therapeutics
Associate Professor, Molecular Medicine Ireland

Publications and Further Research Outputs

Peer-Reviewed Publications

Ward M., Spiers J.P., Protein Phosphatase 2A (PP2A) Regulation of Markers of Extracellular Matrix Remodelling in HCC Cells: Functional Consequences for Tumour Invasion, British Journal of Pharmacology, 2017 Journal Article, 2017 DOI

Alan Kennedy, Postprandial adiponectin and gelatinase response to a high-fat versus an isoenergetic low-fat meal in lean, healthy men, Nutrition, 31, (6), 2015, p863 - 870 Journal Article, 2015 URL DOI

Kennedy, A. Doherty , D.G Petrasca, A. Hennessy, M. Spiers, J.P., HIV-1 Tat clade-specific cytokine induction in monocytes/macrophages is not evidenced in total or Vγ9Vδ2 T lymphocytes, AIDS, 28, 2014, p131 - 133 Journal Article, 2014 DOI

J Svärd, F Blanco, D Nevin, D Fayne, F Mulcahy, M Hennessy and JP Spiers, DIFFERENTIAL INTERACTIONS OF ANTIRETROVIRAL AGENTS WITH LXR, ER AND GR NUCLEAR RECEPTORS - POTENTIAL CONTRIBUTING FACTORS OF ADVERSE EVENTS, British Journal of Pharmacology, 171, 2014, p480 - 497 Journal Article, 2014 TARA - Full Text DOI

Rietz A, Spiers JP, The relationship between the matrix metalloproteinase system, adrenoceptors and phosphoprotein phosphatases , British Journal of Pharmacology, 166, 2012, p1225-1243 Review, 2012 DOI

Abulhul E, McDonald K, Martos R, Phelan D, Spiers JP, Hennessy M, Baugh J, Watson C, O'Loughlin C, Ledwidge M, Long-Term Statin Therapy in Patients With Systolic Heart Failure and Normal Cholesterol: Effects on Elevated Serum Markers of Collagen Turnover, Inflammation, and B-Type Natriuretic Peptide., Clinical therapeutics, 34, (1), 2012, p91 - 100 Journal Article, 2012

Rietz, A. Volkov, Y. Davies, A. Hennessy, M. Spiers, J., Okadaic acid induces MMP-9 expression in fibroblast: Crosstalk between protein phosphatase inhibition and β-adrenoceptor signalling, British Journal of Pharmacology, 165, 2012, p274 - 288 Journal Article, 2012

Kennedy,A.; Hennessy,M.; Bergin,C.; Mulcahy,F.; Hopkins,S.; Spiers,J.P., Ribavirin and interferon alter MMP-9 abundance in vitro and in HIV/HCV co-infected patients, Antiviral Therapy, 16, 2011, p1237 - 1247 Journal Article, 2011

Svard,J.; Spiers,J.P.; Mulcahy,F.; Hennessy,M., Nuclear receptor-mediated induction of CYP450 by antiretrovirals: Functional consequences of NR1I2 (PXR)polymorphisms and differential prevalence in whites and Sub-Saharan Africans, Journal of Acquired Immune Deficiency Syndrome, 55, 2010, p536 - 549 Journal Article, 2010

Davies,A.M.; Volkov,Y.; Spiers,J.P., Automated drug discovery. Development of cardiac cell based assays to study drug efficacy and toxicity, Screening, 3, 2008, p2 - 5 Journal Article, 2008

Volkov Y., Spiers J.P., Davies A.M., Development of cardiac cell based assays for study of cardiac disease - in with the new by automating the old., European Pharmaceutical Review, 6, 2008, p18 - 20 Journal Article, 2008 URL

Gong,K.; Song,G.; Spiers,J.P.; Kelso,E.J.; Zhang,Z., Activation of immune and inflammatory systems in chronic heart failure: novel therapeutic approaches, International Journal of Clinical Practice, 2007 Journal Article, 2007

S. Zhou, J. Feely, J.P. Spiers, A. Mahmud, Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension, Journal of Human Hypertension, 21, (11), 2007, p861 - 867 Journal Article, 2007

Hennessy, M.; Spiers, J.P., A primer on the mechanics of P-glycoprotein the multi drug transporter, Pharmacological Research, 55, 2007, p1 - 15 Review Article, 2007

McDermott,B.J.; McWilliams,S.; Smyth,K.; Kelso,E.J.; Spiers,J.P.; Bell,D.; Murakhur,R.J., Cardiomyocyte function by propofol during stimulated ischaemia is associated with direct action to reduce pro-oxidant activity, Journal of Molecular and Cellular Cardiology, 2007 Journal Article, 2007

Song,G.; Hennessy,M.; Zhao,Y.L.; Li,Q.; Han,W.D.; Qi,Y.; Zhao,W.N.; Silke,B.; Barry,M.; Doyle,R.; Spiers,J.P., Adrenoceptor blockade alters plasma gelatinase activity in patients with heart failure and MMP-9 promoter activity in a human cell line (ECV304), Pharmacological Research, 54, 2006, p57 - 64 Journal Article, 2006

McNulty,M.; Mahmud,A.; Spiers,J.P.; Feely,J., Collagen type-I degradation is related to arterial stiffness in hypertensive and normotensive subjects, Journal of Human Hypertension, 20, 2006, p867 - 873 Journal Article, 2006

McNulty,M.; Spiers,J.P.; McGovern,E.; Feely,J., Ageing is associated with increased matrix metalloproteinase-2 activity in the human aorta., American Journal of Hypertension , 18, 2005, p504 - 509 Journal Article, 2005

Spiers,J.P.; Kelso,E.J.; Fong,S.; Edge,G.; Song,G.; McDermott,B.J.; Hennessy,M., Alterations in vascular matrix metalloproteinase due to ageing and chronic hypertension: effects of endothelin receptor blockade, Journal of Hypertension, 23, 2005, p1717 - 1724 Journal Article, 2005

Hennessy,M.; Clarke,S.; Spiers,J.P.; Kelleher,D.; Mulcahy,F.; Hoggard,P.; Back,D.; Barry,M., Intracellular accumulation of nelfinavir and its relationship to P-glycoprotein expression and function in HIV infected patients, Antiviral Therapy, 9, 2004, p115 - 122 Journal Article, 2004

Meng,X.; Wang,Y.; Zhuang,J.; Yu,Y.; Chen,Y.; Jin,Y.; Wang,Y.; Han,X.; Spiers,J.P.; Song,G., Dynamic changes of myocardial matrix metalloproteinases activities in mice with viral myocarditis, Chinese Medical Journal, 117, 2004, p1195 - 1199 Journal Article, 2004

Hennessy,M.; Clarke,S.; Spiers,J.P.; Mulcahy,F.; Kelleher,D.; Meadon,E.; Maher,B.; Bergin,C.; Tjia,J.; Hoggard,P.; Back,D.; Barry,M., Intracellular indinavir pharmacokinetics in HIV infected patients: comparison with plasma pharmacokinetics, Antiviral Therapy, 8, 2003, p191 - 198 Journal Article, 2003

M. Hennessy, D. Kelleher, J. P. Spiers, M. Barry, P. Kavanagh, D. Back, F. Mulcahy and J. Feely, St Johns wort increases expression of P-glycoprotein: implications for drug interactions, British Journal of Clinical Pharmacology, 53, (1), 2002, p75-82 Journal Article, 2002 TARA - Full Text DOI URL

Nicholl,S.M.; Bell,D.; Spiers,J.P.; McDermott,B.J., Neuropeptide Y Y1 receptor regulates protein turnover and constitutive gene expression in hypertrophying cardiomyocytes, European Journal of Pharmacology, 441, 2002, p23 - 34 Journal Article, 2002

Spiers,J.P.; Dorman,A.; Allen,J.D.; Kelso,E.J.; Silke,B.; McDermott,B.J., Myocardial expression of the endothelin system in endotoxin-treated rats, Journal of Cardiovascular Pharmacology, 38, 2001, p259 - 267 Journal Article, 2001

Spiers,J.P.; Kelso,E.J.; Allen,J.D.; Silke,B.; McDermott,B.J., Inotropic response to endothelin-1, isoprenaline and calcium in cardiomyocytes isolated from endotoxin treated rats: effects of ethyl-isothiourea and dexamethasone, British Journal of Pharmacology, 130, 2000, p1275 - 1282 Journal Article, 2000

Kelso,E.J.; McDermott,B.; Silke,B.; Spiers,J.P., Positive effect of bumetanide on contractile activity of ventricular cardiomyocytes, European Journal of Pharmacology, 400, 2000, p43 - 50 Journal Article, 2000

Kelso,E.J.; McDermott,B.J.; Silke,B.; Spiers,J.P., EndothelinA receptor-subtype mediates endothelin-induced contractility in left ventricular cardiomyocytes isolated from rabbit myocardium, Journal of Pharmacology and Experimental Therapeutics, 294, 2000, p1047 - 1052 Journal Article, 2000

Kelso,E.J.; Spiers,J.P.; McDermott,B.J.; Scholfield,C.N.; Silke,B., Receptor-mediated effects of endothelin on the L-type Ca2+ current in ventricular cardiomyocytes, Journal of Pharmacology and Experimental Therapeutics, 286, 1998, p662 - 669 Journal Article, 1998

Kelso,E.J.; Spiers,J.P.; McDermott,B.J.; Scholfield,C.N.; Silke,B., Stimulation of L-type Ca2+ current by the endothelin receptor A-selective antagonist, BQ-123 in ventricular cardiomyocytes isolated from the rabbit myocardium, Biochemical Pharmacology, 55, 1998, p897 - 902 Journal Article, 1998

Silke,B.; de la Motte,S.; Spiers,J.P.; Herity,N.A.; Drake,M.; Kelly,J.; Harrison,F.J., Haemodynamic effects of intravenous elgodipine in coronary artery disease during rest and exercise, and basic pharmacokinetic parameters, Cardiovascular Drugs Therapy, 10, 1996, p573 - 580 Journal Article, 1996

Kelso,E.J.; Spiers,J.P.; McDermott,B.J.; Scholfield,C.N.; Silke,B., Dual effects of endothelin-1 on the L-type Ca2+ current in ventricular cardiomyocytes, European Journal of Pharmacology, 308, 1996, p351 - 355 Journal Article, 1996

Spiers,J.P.; Kelso,E.J.; McDermott,B.J.; Scholfield,C.N.; Silke,B., Endothelin-1 mediated inhibition of the acetylcholine-activated potassium current from rabbit isolated atrial cardiomyocytes, British Journal of Pharmacology, 119, 1996, p1427 - 1437 Journal Article, 1996

Silke,B.; Spiers,J.P.; Herity,N.A.; Drake,M., Seismocardiography during pharmacodynamic intervention in man, Automedica, 16, 1994, p35 - 44 Journal Article, 1994

Silke,B.; Spiers,J.P.; Boyd,S.; Graham,E.; McParland,G.; Scott,M.E., Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency, Clinical Autonomic Research, 4, 1994, p49 - 56 Journal Article, 1994

Spiers,J.P.; Silke,B.; McDermott,U.; Shanks,R.G.; Harron,D.W., Time and frequency domain assessment of heart rate variability: a theoretical and clinical appreciation, Clinical Autonomic Reserach, 3, 1993, p145 - 158 Journal Article, 1993

Spiers,J.P.; Harron,D.W.; Wilson,R., Duration of action and effect on baroreflex function of the anti-arrhythmic a1 antagonist UK-52,046, Journal of Pharmacy and Pharmacology, 43, 1991, p70 - 72 Journal Article, 1991

Spiers,J.P.; Harron,D.W.; Wilson,R., Acute and chronic effects of rilmenidine on baroreflex function in conscious dogs, European Journal of Pharmacology, 181, 1990, p235 - 240 Journal Article, 1990

Spiers,J.P.; Harron,D.W.; Wilson,R., UK-52,046 (a novel a1-adrenoceptor antagonist) and the role of a-adrenoceptor stimulation and blockade on atrioventricular conduction, Journal of Cardiovascular Pharmacology, 16, 1990, p824 - 830 Journal Article, 1990

Research Expertise

Description

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.

Projects

  • Title
    • Cardiovascular Remodeling in Heart Failure
  • 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
  • Date From
    • 2002
  • Date To
    • 2004
  • Title
    • Novel Mechanism Associated with the Development of Heart Failure
  • 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
  • Date From
    • 2003
  • Date To
    • 2005

Keywords

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; P-GLYCOPROTEIN; Pathophysiology; PEPTIDES; PREGNANE-X RECEPTOR; RELEASE; REMODELING; RITONAVIR; SEPSIS; SMOOTH-MUSCLE CELLS; ST JOHN'S WORT; Vascular Biology, Thrombosis

Recognition

Awards and Honours

Provost's Teaching Award 2008

Wellcome Trust Travelling Fellowship 2002

Harold McCauley Scholarship for Cardiovascular Research 1995

Samuel Haslett Brown Scholarship 1990

Memberships

European Society for Cardiology 2003 – present

International Society for Heart Research 1997 – present

British Society for Cardiovascular Research 1997 – present

British Pharmacological Society 1992 – present

Irish Association of Pharmacologists 1990 – present

American Heart Association 2005 – present


Last updated 21 September 2016 oneillm1@tcd.ie (Email).