Michael J Dunn

Beaumont Hospital, Dublin, Leinster, Ireland

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Publications (268)1260.67 Total impact

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    ABSTRACT: The Cardiovascular Initiative (CVI) of the Human Proteome Organisation (HUPO) held its fifth workshop prior to the Sixth Annual HUPO World Congress in Seoul, Korea in October 2007. The objectives of this report are as follows: to trace the (relatively brief) history of the CVI for those who may not be acquainted with it; to highlight lectures given by members of the CVI during this Workshop; and to make the community aware of the aims of this Initiative, including collaborative projects currently under consideration.
    Proteomics 03/2008; 8(5):924-6. DOI:10.1002/pmic.200701083 · 3.97 Impact Factor
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    ABSTRACT: Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis that PLM is part of the cardiac Na-K pump complex and provides the link between kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca exchanger activity and may be involved in cell volume regulation. This study characterized the phenotype of the PLM knockout (KO) mouse heart to further our understanding of PLM function in the heart. PLM KO mice were bred on a congenic C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly depressed cardiac contractile function in PLM KO mice, which was exacerbated when hearts were isolated and Langendorff perfused. There were no significant differences in action potential morphology in paced Langendorff-perfused hearts. Depressed contractile function was associated with a mild cardiac hypertrophy in PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild-type controls. SDS-PAGE and Western blot analysis of ventricular homogenates revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal changes in ventricular protein expression, indicating that deletion of PLM was the primary reason for the observed PLM KO phenotype. These studies demonstrate that PLM plays an important role in the contractile function of the normoxic mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K-ATPase activity, indirectly affecting intracellular Ca and hence contractile function.
    AJP Heart and Circulatory Physiology 03/2008; 294(2):H613-21. DOI:10.1152/ajpheart.01332.2007 · 4.01 Impact Factor
  • Michael J. Dunn
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    ABSTRACT: The ability of two-dimensional electrophoresis (2-DE) to separate complex mixtures of proteins, such as represented by cells, tissues, and even whole organisms, has been recognized for more than 20 yr (1). Using “standard”-format (around 20×20 cm) 2-D gels, the method is capable of routinely separating 2000 proteins from whole-cell and tissue extracts. The resolution capacity can be extended significantly (up to 5000–10,000 proteins) using large-format (40×30 cm) 2-D gels (2). Over the last 20 yr, 2-DE has been used primarily as an analytical tool for the characterization of proteins by their charge (pI), size (M r), and relative abundance. Specialized computer software has been developed for the qualitative and quantitative analysis of 2-DE protein patterns (3), and these systems have been used to construct several comprehensive databases of protein expression in a variety of cell types and tissues (for examples, see ref. 4).
    02/2008: pages 313-318;
  • Michael J. Dunn
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    ABSTRACT: Since the first complete genome sequence, that of the bacterium Haemophilus influenzae, was published in 1995 (1), a flurry of activity has seen the completion of the genomic sequences for more than 149 organisms (16 archael, 114 bacterial, and 19 eukaryotic). An up-to-date list of completed genomes is maintained on the GOLD website (Genomes OnLine Database, http://igweb.integratedgenomics.com/GOLD). Early in 2001, a major milestone was reached with the completion of the human genome sequence (2,3). A major challenge in the postgenome era will be to elucidate the biological function of the large number of novel gene products that have been revealed by the genome sequencing initiatives, to understand their role in health and disease, and to exploit this information to develop new diagnostic and therapeutic agents. The assignment of protein function will require detailed and direct analysis of the patterns of expression, interaction, localization, and structure of the proteins encoded by genomes; the area now known as “proteomics” (4).
    02/2008: pages 345-352;
  • Michael J. Dunn
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    ABSTRACT: The ability of two-dimensional electrophoresis (2-DE), based on the original method developed more than 20 years ago (1), to separate simultaneously up to several thousand proteins using large-format gels (2) has made it the method of choice for the analysis of protein expression in complex biological systems, such as whole cells, tissues, and organisms. Initially, 2-DE only yielded information on the charge (pI), size (M r), and relative abundance of the separated proteins. However, in recent years, a variety of methods have been developed that make it possible to identify and characterize proteins separated by 2-DE. Many of these methods depend on the technique of Western electroblotting in which proteins separated by 2-DE are transferred (“blotted”) by the application of an electric field perpendicular to the plane of the gel onto the surface of an inert membrane, such as nitrocellulose (3). Methods for electroblotting of protein from 2-DE gels are described in Chapter 35.
    02/2008: pages 319-329;
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    ABSTRACT: The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P<0.001), BASP1 (40% difference; P<0.05) and LAMP (22% difference; P<0.01)) and BPD (STXBP1 (31% difference; P<0.001), BASP1 (23% difference; P<0.01) and LAMP (20% difference; P<0.01)) in the Stanley brain series (n=20 per group). Further validation in dlpfc from the Harvard brain subseries (n=10 per group) confirmed increased protein expression in SCZ of STXBP1 (18% difference; P<0.0001), BASP1 (14% difference; P<0.0001) but not LAMP (20% difference; P=0.14). No significant differences in STXBP1, BASP1 or LAMP protein expression in BPD dlpfc were observed. This study, through proteomic assessments of MM in dlpfc and validation in two brain series, strongly implicates LAMP, STXBP1 and BASP1 in SCZ and supports the view of a neuritic and synaptic dysfunction in the neuropathology of SCZ.
    Molecular Psychiatry 02/2008; 14(6):601-13. DOI:10.1038/mp.2008.7 · 15.15 Impact Factor
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    ABSTRACT: Proteomic technologies, such as yeast twohybrid, mass spectrometry (MS), protein/ peptide arrays and fluorescence microscopy, yield multi-dimensional data sets, which are often quite large and either not published or published as supplementary information that is not easily searchable. Without a system in place for standardizing and sharing data, it is not fruitful for the biomedical community to contribute these types of data to centralized repositories. Even more difficult is the annotation and display of pertinent information in the context of the corresponding proteins. Wikipedia, an online encyclopedia that anyone can edit, has already proven quite successful1 and can be used as a model for sharing biological data. However, the need for experimental evidence, data standardization and ownership of data creates scientific obstacles.
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    ABSTRACT: There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P<0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.
    Molecular Psychiatry 11/2007; 13(12):1102-17. DOI:10.1038/sj.mp.4002098 · 15.15 Impact Factor
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    ABSTRACT: Both the generation and the analysis of proteomics data are now widespread, and high-throughput approaches are commonplace. Protocols continue to increase in complexity as methods and technologies evolve and diversify. To encourage the standardized collection, integration, storage and dissemination of proteomics data, the Human Proteome Organization's Proteomics Standards Initiative develops guidance modules for reporting the use of techniques such as gel electrophoresis and mass spectrometry. This paper describes the processes and principles underpinning the development of these modules; discusses the ramifications for various interest groups such as experimentalists, funders, publishers and the private sector; addresses the issue of overlap with other reporting guidelines; and highlights the criticality of appropriate tools and resources in enabling 'MIAPE-compliant' reporting.
    Nature Biotechnology 09/2007; 25(8):887-93. DOI:10.1038/nbt1329 · 39.08 Impact Factor
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    ABSTRACT: Skeletal muscle fibre transitions occur in many biological processes, in response to alterations in neuromuscular activity, in muscular disorders, during age-induced muscle wasting and in myogenesis. It was therefore of interest to perform a comprehensive proteomic profiling of muscle transformation. Chronic low-frequency stimulation of the rabbit tibialis anterior muscle represents an established model system for studying the response of fast fibres to enhanced neuromuscular activity under conditions of maximum activation. We have conducted a DIGE analysis of unstimulated control specimens versus 14- and 60-day conditioned muscles. A differential expression pattern was observed for 41 protein species with 29 increased and 12 decreased muscle proteins. Identified classes of proteins that are changed during the fast-to-slow transition process belong to the contractile machinery, ion homeostasis, excitation-contraction coupling, capillarization, metabolism and stress response. Results from immunoblotting agreed with the conversion of the metabolic, regulatory and contractile molecular apparatus to support muscle fibres with slower twitch characteristics. Besides confirming established muscle elements as reliable transition markers, this proteomics-based study has established the actin-binding protein cofilin-2 and the endothelial marker transgelin as novel biomarkers for evaluating muscle transformation.
    PROTEOMICS 09/2007; 7(18):3417-30. DOI:10.1002/pmic.200700262 · 3.97 Impact Factor
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    ABSTRACT: Pulmonary fibrosis arises as a consequence of aberrant remodeling and defective repair mechanisms within the lung. This destructive process is the cause of much of the morbidity and mortality in many pulmonary disorders. Unfortunately, therapeutic options are limited. A significant advancement in the management of patients with pulmonary fibrosis would be the identification of biomarkers for diagnosis, prognosis and prediction of patient response to therapy. Bronchoalveolar lavage is an ideal tissue target for the discovery of these potential biomarkers in pulmonary fibrosis. Integrative approaches using both gel- and mass spectrometry-based proteomic workflows will allow full coverage of this complex proteome, thereby unlocking this potential information as a clinical tool to aid diagnosis and guide treatment for individual patients with pulmonary fibrosis.
    Expert Review of Proteomics 07/2007; 4(3):379-88. DOI:10.1586/14789450.4.3.379 · 3.54 Impact Factor
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    Marlene L Rose, Michael J Dunn
    Circulation 06/2007; 115(17):e434; author reply e435. DOI:10.1161/CIRCULATIONAHA.106.668517 · 14.95 Impact Factor
  • Emma McGregor, Michael J. Dunn
    05/2007: pages 19-55;
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    ABSTRACT: Prostate cancer is the commonest solid-organ malignancy to affect men in Europe and the USA; it is estimated that one in six men will develop this cancer in their lifetime. Current screening relies on a digital rectal examination with a serum prostate-specific antigen test. Novel urinary diagnostic tests are potentially interesting screening tools for this disease. We examined published reports assessing the use of urinary markers for the diagnosis of prostate cancer. Using a PubMed-based search we identified studies of urinary markers for prostate cancer published from 1985 to February 2006 using the search terms 'urine', 'marker' and 'prostate cancer'. Studies to date have used small cohorts and relied on prostatic biopsies to provide histology. The sensitivity and specificity of markers are wide ranging but with only a few studies published on each putative marker it is difficult to assess their potential impact. Using urinary biomarkers for prostate cancer is a relatively novel diagnostic approach; they are appealing as a screening test because they are not invasive. Further work is needed to identify and validate 'signature markers' indicative of prostatic malignancy. The newer proteomic platforms are promising biomarker discovery tools that might uncover the next generation of urinary biomarkers.
    BJU International 03/2007; 99(2):263-8. DOI:10.1111/j.1464-410X.2006.06610.x · 3.13 Impact Factor
  • Michael J Dunn
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    ABSTRACT: The majority of cardiovascular proteomic investigations reported to date have employed two-dimensional gel electrophoresis (2DE) with immobilized pH gradients to separate the sample proteins, combined with quantitative computer analysis to detect differentially expressed proteins and mass spectrometry technologies to identify proteins of interest. In spite of the development of novel gel-free technologies, 2DE remains the only technique that routinely can be applied to parallel quantitative expression profiling of large sets of complex protein mixtures, such as those represented by cardiovascular cell and tissue lysates. This chapter details a procedure for large-format 2DE, and its variations, that has been successfully applied in cardiovascular proteomic research.
    Methods in Molecular Biology 02/2007; 357:3-13. DOI:10.1385/1-59745-214-9:3 · 1.29 Impact Factor
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    ABSTRACT: In a proteomic approach using 2-DE, the changes in protein expression patterns in wing imaginal discs induced by hormone treatment have been studied. Here we show the response of butterfly imaginal wing disc tissue taken from late fifth instar larvae of the African-Mocker swallowtail Papilio dardanus (Lepidoptera) to the insect hormones 20-hydroxyecdysone (20-HE) and juvenile hormone (JH). The tissues were cultured in the presence of one hormone or a combination of both and their protein expression was compared to the pattern obtained from untreated wing discs. All the treatments resulted in changes in the expression pattern distinct from the uninduced control, indicating a distinct protein regulation induced by the hormones. The treatment with both of the hormones, which are known to have antagonistic physiological effects, did show a unique pattern, presumably the result, in part, of synergistic effects on protein expression mediated by the combined effects of both the hormones. The extent of the interaction between JH and 20-HE indicates a complex molecular regulation, far beyond a simple antagonistic effect.
    Electrophoresis 02/2007; 28(4):535-44. DOI:10.1002/elps.200600620 · 3.16 Impact Factor
  • Michael J. Dunn
    Journal of Chemical Technology & Biotechnology 01/2007; 51(1):119-23. DOI:10.1002/jctb.280510114 · 2.49 Impact Factor
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    ABSTRACT: The development of ECL-Plex CyDye-conjugated secondary antibodies allows the advancement of conventional Western blotting, opening up possibilities for highly sensitive and quantitative protein confirmation and identification. We report a novel proteomic method to simultaneously visualise the total protein profile as well as the specific immunodetection of an individual protein species by combining cyanine CyDye pre-labelled proteins and antibody immunoblotting. This technique proposes to revolutionise both 2-D immunoprobing and protein confirmation following MS analysis.
    PROTEOMICS 12/2006; 6(24):6400-4. DOI:10.1002/pmic.200600139 · 3.97 Impact Factor
  • Michael J. Dunn
    Proteomics 12/2006; 6(24):6389-6389. DOI:10.1002/pmic.200690151 · 3.97 Impact Factor
  • Michael J. Dunn
    Proteomics 11/2006; 6(21):5675-5675. DOI:10.1002/pmic.200690127 · 3.97 Impact Factor

Publication Stats

9k Citations
1,260.67 Total Impact Points

Institutions

  • 2005–2014
    • Beaumont Hospital
      Dublin, Leinster, Ireland
    • University College Dublin
      • • Conway Institute of Biomolecular & Biomedical Research
      • • School of Medicine & Medical Science
      Dublin, Leinster, Ireland
  • 2011
    • Royal College of Surgeons in Ireland
      • Department of Psychiatry
      Dublin, L, Ireland
  • 1999–2011
    • Imperial College London
      Londinium, England, United Kingdom
  • 2010
    • University of Coimbra
      • Centro de Neurociências e Biologia Celular (CNC)
      Coimbra, Distrito de Coimbra, Portugal
  • 2009
    • TobaccoFree Research Institute Ireland
      Dublin, Leinster, Ireland
    • Wellcome Trust
      Londinium, England, United Kingdom
  • 2008
    • Mater Misericordiae University Hospital
      Dublin, Leinster, Ireland
  • 2003–2008
    • King's College London
      • • Institute of Psychiatry
      • • Department of Neuroscience (IoP)
      London, ENG, United Kingdom
    • The University of Arizona
      Tucson, Arizona, United States
    • Royal Brompton and Harefield NHS Foundation Trust
      • Cardiothoracic Surgery & Transplantation Unit
      Harefield, England, United Kingdom
  • 1989–2008
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1991–2007
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 2004–2005
    • UK Department of Health
      Londinium, England, United Kingdom
  • 2003–2005
    • ICL
      Londinium, England, United Kingdom
  • 2001
    • University of Sussex
      Brighton, England, United Kingdom
  • 1998
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 1997
    • University of Liverpool
      Liverpool, England, United Kingdom
    • Imperial Valley College
      Middlesex, New Jersey, United States
  • 1995
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 1994
    • Royal Veterinary College
      Londinium, England, United Kingdom
  • 1984
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany