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

Publications and Further Research Outputs

Peer-Reviewed Publications

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 Journal Article, 2019 DOI

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, Cardiovascular Diabetology, 2019 Journal Article, 2019

Casey, G. and Spiers, J.P., The role of PP2A in an inflammatory induced increase in Brain Microvascular Permeability, WCP2018 Kyoto, Japan, 2018, ppOR10-1 Oral Presentation, 2018 URL

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, 2018 DOI

Casey, G. and Spiers, J.P., PP2A: a guardian at the gates?, Heart, Scottish Cardiovascular Forum, Dublin, 104, Heart, 2018, ppA1 Oral Presentation, 2018 DOI

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, 174, 2017, p1116 - 1130 Journal Article, 2017 DOI

Casey, G. and Spiers, J.P. , The role of PP2A in brain microvascular permeability, pA2 online, Pharmacology 2017, London, British Pharmacological Society, 2017, pp066P Meeting Abstract, 2017 URL

Casey, G. and Ward, M. and Spiers, J.P. , The role of PP2A and related proteins in Human Brain Microvascular Endothelial Cells in response to Pro and Anti-Inflammatory Cytokines, pA2 online, Pharmacology 16, London, British Pharmacology Society, 2016, pp176P Meeting Abstract, 2016 URL

Harkin, K. and Metcalfe, A. and Harbinson, M. and Campbell, M. and Spiers, J.P. and Bell, D., Influence of intermedin/adrenomedullin-2 on nephrotoxic drug-related injury to human renal mesangial and tubular epithelial cells, pA2 online, Pharmacology 2016, London, British Pharmacological Society, 2016, pp222P Meeting Abstract, 2016 URL

Kennedy, A., Spiers, J. P., Crowley, V., Williams, E., Lithander, F. E., 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 DOI URL

Ward, M.P. and Spiers, J.P., Serine/Threonine Protein Phosphatase regulation of Matrix Metalloproteinase 9 in Hepatocellular Carcinoma, WCP2014, Capetown South Africa, 2014 Oral Presentation, 2014

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 DOI TARA - Full Text

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

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

Benito MJ, Patterson A, Spiers JP, , First Experience Introducing Research Projects in Medicine: Students' Feedback on a New Approach to Research. I, INMED Conference 2011, Flexner 100 years on - a return to core principles, Trinity College Dublin, 18-20 May, 2011, 2011 Poster, 2011

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

Alshareif, O. and Hennessy, M. and Matthew, M. and Keane, J. and Spiers, J.P., Rosiglitazone inhibits MMP-9 protein expression through NF-?B and AP-1 dependent mechanisms in human THP-1 cells, pA2 online, Winter meeting of the British Pharmacological Society, London, British Pharmacological Society, 2009, pp067P Meeting Abstract, 2009 URL

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

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

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

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

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

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

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

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

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

M. McNulty, J.P. Spiers, E. McGovern, J. Feely, Selective increase in matrix metalloproteinase-2 activity in the ageing human aorta, Proceedings of the Fourth Meeting of European Association for Research on Arterial Structure and Physiology, 2004, PA21 Meeting Abstract, 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

Siah, W.E. and Kelso, E. J. and Hennessy, M. and Edge, G. and McDermott, B.J. and Spiers, J.P., Role of endothelin in regulation of matrix metalloproteinase activity in hypertension-induced hypertrophy and transition to failure using spontaneously hypertensive rats, pA2 online, Winter meeting of the British Pharmacological Society, London, British Pharmacology Society, 2004, pp086PGKT Meeting Abstract, 2004 URL

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. McNulty, P. Spiers, E. McGovern, J. Feely, Differential expression of matrix metalloproteinase-2 and -9 in the aorta and internal mammary artery of patients undergoing coronary artery bypass grafts, British Journal of Clinical Pharmacology, 55, 2003, pp435 - 436 Meeting Abstract, 2003

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

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 URL TARA - Full Text DOI

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

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.; 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

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.; 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

Kelso, E. J. and Spiers, J. P. and McDermott, B. J. and Scholfield, C. N. and Silke, B., Effects of endothelin (ET) receptor selective and non-selective antagonists on ET-1-inhibites L-type Ca2+ currents in ventricuar cardiomyocytes isolated from rabbit myocardium, British Journal of Pharmacology, 118, 1996, pp56P Conference Paper, 1996

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

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

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

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., 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

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

Phillips, M. and Svard, J. and Spiers, J.P. and Mulcahy, F. and Hennessy, M., Efavirenz levels, dizziness and tests of neurocognition in a Dublin HIV cohort, British HIV Association Conference Paper,

McNulty, M. and Mahmud, A. and Spiers, J. P. and Feely, J., Arterial stiffness and collagen type-1 turnover in normo- and hypertensive subjects, Irish-Belgium Meeting Conference Paper,

Rietz, A. and Hennessy, M. and Davies, A. and Volkov, Y. and Spiers, J.P., Adrenoceptor agonists do not alter matrix metalloproteinase-9 (MMP-9) activity and promoter activity in murine fibroblasts (NIH3T3): Lack of involvement of NFκB, Heart Failure Congress, 8, European Journal of Heart Failure, ppA1270 Conference Paper,

Kennedy, A. and Doherty, D. and Hennessy, M. and Spiers, J.P., HIV-1 Tat clade B increases interferon-gamma production by gamma delta T-cells, Annual Scientific Meeting of the Infectious Diseases Society of Ireland Conference Paper,

Kennedy, A. and Hennessy, M. and Bergin, C. and Mulcahy, F. and Hopkins, S. and Spiers, J.P., Matrix metalloproteinase-9 (MMP-9) is altered by ribavirin and interferon in THP-1 cells and in HIV/HCV co-infected patients, Controversies in the Management of Viral Hepatitis Conference Paper,

Hennessy, M. and Hopkins, S. and Spiers, J. P. and Back, D. and Kewn, S. and Bergin, C. and Mulcahy, F., Haematological toxicity, ribavirin and intracellular triphosphate levels in HIV/HCV infected patients receiving interferon and ribavirin, British Journal of Pharmacology, in press Conference Paper,

Kelso, E. J. and McDermott, B. and Silke, B. and Spiers, J.P., ETA receptor-subtype mediates the dual effects of endothelin on the L-type Ca2+ current in ventricular cardiomyocytes isolated from rabbit myocardium, International Society for Heart Research, 29, Journal of Molecular and Cellular Cardiology Conference Paper,

Ward, M.P. and Botting, C.H. and Lucitt, M.B. and Spiers, J.P., Identification of Phosphoproteins Regulated by Protein Phosphatase 2A Inhibition in Human Hepatocellular Carcinoma , Pharmacology 14, British Pharmacology Society Conference Paper,

Kelso, E. J. and McDermott, B. and Silke, B. and Spiers, J.P., Influence of endothelin on the L-type calcium current in ventricular cardiomyocytes isolated from rabbit myocardium, International Society for Heart Research, European Heart Journal Conference Paper,

Ward, M.P. and Spiers, J.P., Modulation of MMP-9 and TIMP-1 expression by Protein Phosphatase in Hep3B and LX-2 cell lines, Pharmacology 13, British Pharmacological Society Conference Paper,

Rietz, A. and Hennessy, M. and Davies, A. and Volkov, Y. and Spiers, J.P., Combined blockade of α1 and β-adrenoceptors is essential for inhibtion of TNFα-induced MMP-9 expression and activity in NIH3T3 fibroblasts, British Pharmacological Society Winter Meeting Conference Paper,

Hopkins, S. and Hennessy, M. and Spiers, J. P. and Clarke, S. and Barry, M. and Mulcahy, F. and Bergin, C., The effect of interferon therapy on plasma MMP activity in HIV/HCV co-infected patients, Retroviruses, Chicago Conference Paper,

McNulty, M. and Mahmud, A. and Spiers, J. P. and Feely, J., Arterial stiffness and collagen type-1 turnover in normo- and hypertensive subjects, Irish-Belgium Meeting Conference Paper,

Kelso, E. J. and McDermott, B. J. and Silke, B. and Spiers, J. P., Contractile effects of endothelin-1 and endothelin-3, mediated by ET A and ET B receptor subtypes, in ventricular cardiomyocytes isolated from rabbit myocardium, British Journal of Pharmacology, 118, pp131P Conference Paper,

Ward, M. and Spiers, J.P., Increased Cancerous Inhibitor of PP2A (CIP2A) Expression in Hepatocellular Carcinoma Cells Following Co-Culture With Anti-Inflammatory Macrophages, Pharmacology 15, British Pharmacological Society Conference Paper,

Svard, J. and Spiers, J.P. and Mulcahy, F. and Hennessy, M., Antivirals and nuclear receptor activation of CYP3A4 and 2B6, HIV 9 Conference Paper,

Svard, J. and Spiers, J.P. and Mulcahy, F. and Hennessy, M., Anivirals and nuclear receptor activation of CYP3A4 and 2B6, Infectious Diseases Society of Ireland Conference Paper,

Svard, J. and Spiers, J.P. and Mulcahy, F. and Hennessy, M., Genetic variability in PXR, MDR-1, CYP3A4 and CYP2B6 in HIV infected caucasian and sub-Saharan African patients - benefits from a cohort approach, British Pharmacological Society Winter Meeting Conference Paper,

Spiers, J.P. and Hennessy, M., Development of an interactive web-based revision and continual assessment environment for medical students studying pharmacology using Questionmark, Irish Network of Medical educators Conference Paper,

Zhao, P. and Gong, K. and Song, G. and Zhang, Z. and Spiers, J. P., Anti-inflammatory effects of methotrexate improve cardiac function in a rat model of dilated cardiomyopathy, IUPHAR Beijing Conference Paper,

Woo, J. and Spiers, J.P. and Svard, J. and Edwards, C. and Davies, A. and Mulcahy, F. and Hennessy, M., HIV antiretroviral drug-induced toxicity in H9C2 cardiomyoblasts: Effects on oxidative stress, mitochondrial membrane potential, intracellular calcium and cell viability, Infectious Diseases Society of Ireland Conference Paper,

Spiers, J.P. and Kelso, E. J. and Allen, J. D. and Silke, B. and McDermott, B., Free radical damage and the effect of α-phenyl n-tert-butyl nitrone in LPS treated rats, Irish Cardiac Society Conference Paper,

Kennedy, A. and Hennessy, M. and Bergin, C. and Mulcahy, F. and Hopkins, S. and Spiers, J.P., Interferon and ribavirin alter matrix metalloproteinase-9 (MMP-9) activity in HIV/HCV co-infected patients and in THP-1 cells, British Pharmacological Society winter meeting Conference Paper,

Svard, J. and Spiers, J.P. and Mulcahy, F. and Hennessy, M., Activation of liver X receptors (alpha and beta) by HIV protease inhibitors atazanavir and ritonavir and inhibition by non-nucleoside reverse transcriptase inhibitor efavirenz, World Pharma 2010 Conference Paper,

Edge, G. and Kelso, E. J. and Hennessy, M. and McDermott, B. J. and Spiers, J. P., Matrix metalloproteinase (MMP) activity in aorta from spontaneously hypertensive heart failed rats: Effect of chronic endothelin receptor antagonism, British Journal of Pharmacology, 138, pp56P Conference Paper,

Silke, B. and Spiers, J.P. and Herity, N. A. and Zanetti, J.M., Seismocardiography - a new pharmacodynamic method, INternational Symposium on Cardiovascular Pharmacotherapy Conference Paper,

Rietz, A. and Hennessy, M. and Davies, A. and Volkov, Y. and Spiers, J.P., β-Adrenergic stimulation inhibits okadaic acid-induced MMP-9 respnse in fibroblasts: A novel regulatory mechanism, XX World Congress of the International Society for Heart Research Conference Paper,

Siah, W. F. and Kelso, E. J. and Hennessy, M. and Edge, G. and McDermott, B. J. and Spiers, J. P., Aortic matrix metalloproteinase activity in hypertension-induced hypertrophy and transition to failure using spontaneously hypertensive rats, British Journal of Pharmacology, in press Conference Paper,

Kelso, E. J. and McDermott, B. and Spiers, J.P. and Silke, B. and Scholfield, C. N., Dual effects of endothelin-1 on the Ca2+ current from rabbit ventricular cardiomyocytes, International Society for Heart Research, Molecular and Cellular Biochemistry Conference Paper,

Edge, G. and Kelso, E. J. and Hennessy, M. and McDermott, B. and Spiers, J. P., Matrix metalloproteinase (MMP) activity in aorta from spontaneously hypertensive heart failed rats: Effect of chronic endothelin receptor antagonism, Irish Angiology Society Conference Paper,

Woo, J. and Hennessy, M. and Mulcahy, F. and Spiers, J.P., Cardiovascular risk estimation in patients treated with abacavir in the Dublin HIV Cohort, Infesctious Diseases Society of Ireland Conference Paper,

Spiers, J.P. and Edwoards, C. and Hennessy, M. and Mulcahy, F. and Davies, A., Abacarvir does not havre a direct cardiotoxic effect compared to othe antiretroviral agents: Effects on cell death, mitochondrial membrane potential, intracellular calcium and free radical generation, Winter meeting of the British Pharmacological Society, British Journal of Pharmacology Conference Paper,

Hennessy, M. and Spiers, J. P. and Silke, B. and King, G. and Barry, M., Early alterations in plasma markers of remodelling in heart failure patients treated with carvedilol, British Journal of Clinical Pharmacology, 55, pp426-427 Conference Paper,

McNulty, M. and Mahmud, A. and Spiers, J. P. and Feely, J., Arterial stiffness is associated with collagen type-1 degradation in normo- and hypertensive subjects, Journal of Human Hypertension, 18, pps6 Conference Paper,

Rietz, A. and Davies, A. and Hennessy, M. and Volkov, Y. and Spiers, J.P., Adrenoceptor modulation of matrix metalloproteinase-9 (MMP-9) activity and promoter activity in murine fibroblasts (NIH3T3): Not all that is seems!, British Pharmacological Society Winter Meeting Conference Paper,

Hennessy, M. and Spiers, J. P. and Silke, B. and King, G. and Barry, M., Early alterations in plasma markers of remodeling in heart failure patients treated with carvedilol, Irish Angiology Society Conference Paper,

Svard, J. and Spiers, J. P. and Mulcahy, F. and Hennessy, M., Nuclear receptor-mediated expression of CYP3A4 and CYP2B6 by antiretrovirals - implications for prediction of drug interaction potential, British Pharmacological Society Conference Paper,

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
  • 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
  • Funding Agency
    • Health Research Board

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