Michael J Dunn

University College Dublin, Dublin, Leinster, Ireland

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Publications (481)2078.82 Total impact

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    ABSTRACT: Increasing clinical evidence for the effectiveness of herbal antidepressants has led to investigations at the molecular level. Using two-dimensional gel electrophoresis, this study investigated similarities in protein expression between clomipramine, St John's wort and a Chinese herbal formula, xiao-yao-san, often used in mood disorder treatment. HT22 cells, derived from a mouse hippocampal cell line, were treated for 24 h, and protein expression was compared with that of the untreated cells (n = 4/group). Forty-three protein spots were found to be significantly differentially expressed (P < 0.05) in more than one of the treatment groups. Twenty-nine of these were identified using mass spectrometry. The most affected proteins were those involved in the cytoskeleton and energy metabolism, and an up-regulation of vimentin by all three treatments was confirmed by Western blotting. This study provides preliminary evidence for multiple common molecular targets between conventional and alternative antidepressants, which appear to collectively affect neuronal plasticity.
    No preview · Article · Jul 2008 · Journal of Psychopharmacology
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    ABSTRACT: The use of comparative serum proteomic analysis has the potential to reveal protein expression changes present at different stages of disease progression. Depletion strategies allow for the enrichment of low-abundance proteins, which are more likely to be clinically significant biomarkers. We have observed that patient serum samples filtered through 0.22 microm cellulose acetate spin filters prior to depletion showed a variable level of retention of patient material on the upper part of the filter. This could potentially be related to the fasting status of the patient as a reduction in the lipid content of samples through the incorporation of a centrifugation step prior to filtration was found to reduce this effect. In order to determine if proteins were being selectively retained during filtration, a 2-D difference gel electrophoresis (2-D DIGE) experiment was performed. This demonstrated no significant selective retention of protein within crude serum samples. However, as this analysis was carried out on crude serum, it must be emphasised that protein loss could be manifest in the low-abundance proteins which would be masked in our analysis. Depletion of the retentate was not possible due to technical limitations, however based on our results a centrifugation step might act as an alternative to filtration in serum processing prior to depletion.
    No preview · Article · Jul 2008 · Electrophoresis

  • No preview · Article · Jun 2008 · Schizophrenia Research
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    ABSTRACT: Plans for the European Proteomics Association (EuPA) were conceived and established during 2004 and 2005, and culminated in the formal inception of the organisation during the 4th HUPO World Congress held in Munich in 2005. The mission from the outset has been three-tiered and is to: i) strengthen the national Proteomics organizations in their efforts; ii) to co-ordinate and provide educational programs, and iii) to advance the networking of scientists through meetings, workshops and student exchange. Linked to the mission were objectives to emphasise the benefits and contributions of Proteomics to biological and industrial researchers, the general public and science policy makers in Europe. In addition, the EuPA set out to promote scientific exchange for all applications and technology development related to Proteomics, and coordinate joint activities of national Proteomics societies at the European level. To achieve these tasks an organisational structure was conceived whereby four Activity Committees (Conferences/Communications, Education, EuPA-HUPO-Interactions and Funding) were implemented and a General Council consisting of all member countries. The remarkable rise and progress the EuPA has achieved in this small time frame is reported here.
    Full-text · Article · May 2008 · Journal of Proteomics
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    Michael J Dunn

    Preview · Article · May 2008 · WMJ: official publication of the State Medical Society of Wisconsin
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    Andrew W Dowsey · Michael J Dunn · Guang-Zhong Yang
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    ABSTRACT: The quest for high-throughput proteomics has revealed a number of challenges in recent years. Whilst substantial improvements in automated protein separation with liquid chromatography and mass spectrometry (LC/MS), aka 'shotgun' proteomics, have been achieved, large-scale open initiatives such as the Human Proteome Organization (HUPO) Brain Proteome Project have shown that maximal proteome coverage is only possible when LC/MS is complemented by 2D gel electrophoresis (2-DE) studies. Moreover, both separation methods require automated alignment and differential analysis to relieve the bioinformatics bottleneck and so make high-throughput protein biomarker discovery a reality. The purpose of this article is to describe a fully automatic image alignment framework for the integration of 2-DE into a high-throughput differential expression proteomics pipeline. The proposed method is based on robust automated image normalization (RAIN) to circumvent the drawbacks of traditional approaches. These use symbolic representation at the very early stages of the analysis, which introduces persistent errors due to inaccuracies in modelling and alignment. In RAIN, a third-order volume-invariant B-spline model is incorporated into a multi-resolution schema to correct for geometric and expression inhomogeneity at multiple scales. The normalized images can then be compared directly in the image domain for quantitative differential analysis. Through evaluation against an existing state-of-the-art method on real and synthetically warped 2D gels, the proposed analysis framework demonstrates substantial improvements in matching accuracy and differential sensitivity. High-throughput analysis is established through an accelerated GPGPU (general purpose computation on graphics cards) implementation. Supplementary material, software and images used in the validation are available at http://www.proteomegrid.org/rain/.
    Full-text · Article · May 2008 · Bioinformatics

  • No preview · Article · Apr 2008
  • Pamela M. Donoghue · Miroslava Stastna · Michael J. Dunn
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    ABSTRACT: Introduction2DE: Protein Solubilization and Sample Preparation2DE: Protein Separation Focusing in the First DimensionAdvances in IEFImproving Proteomic Coverage by Subcellular FractionationProtein Detection and Image AnalysisThe Future of 2DE Focusing in the First DimensionAdvances in IEF
    No preview · Article · Apr 2008
  • C.A. McManus · M.L. Rose · M.J. Dunn

    No preview · Article · Apr 2008
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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.
    Full-text · Article · Mar 2008 · AJP Heart and Circulatory Physiology
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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.
    No preview · Article · Mar 2008 · Proteomics
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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.
    Full-text · Article · Mar 2008 · Nature Biotechnology
  • 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).
    No preview · Chapter · Feb 2008
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    A T Behan · C Byrne · M J Dunn · G Cagney · D R Cotter
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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.
    Preview · Article · Feb 2008 · Molecular Psychiatry
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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.
    Full-text · Article · Jan 2008
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    Michael J Dunn

    Preview · Article · Nov 2007 · WMJ: official publication of the State Medical Society of Wisconsin
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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.
    Full-text · Article · Nov 2007 · Molecular Psychiatry
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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.
    Full-text · Article · Sep 2007 · Nature Biotechnology
  • Michael J Dunn

    No preview · Article · Sep 2007 · WMJ: official publication of the State Medical Society of Wisconsin
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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.
    No preview · Article · Sep 2007 · PROTEOMICS

Publication Stats

18k Citations
2,078.82 Total Impact Points

Institutions

  • 2005-2015
    • University College Dublin
      • School of Medicine & Medical Science
      Dublin, Leinster, Ireland
    • London Research Institute
      Londinium, England, United Kingdom
  • 2014
    • Beaumont Hospital
      Dublin, Leinster, Ireland
  • 2011
    • St. Vincents University Hospital
      Dublin, Leinster, Ireland
    • Royal College of Surgeons in Ireland
      • Department of Psychiatry
      Dublin, L, Ireland
  • 2003-2011
    • Imperial College London
      • Department of Medicine
      Londinium, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
    • Royal Brompton and Harefield NHS Foundation Trust
      • Cardiothoracic Surgery & Transplantation Unit
      Harefield, England, United Kingdom
  • 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
  • 1997-2008
    • Medical College of Wisconsin
      • • Division of Cardiovascular Medicine
      • • Department of Medicine
      Milwaukee, Wisconsin, United States
    • Imperial Valley College
      Middlesex, New Jersey, United States
  • 1981-2006
    • Case Western Reserve University School of Medicine
      • Department of Medicine
      Cleveland, Ohio, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2004-2005
    • UK Department of Health
      Londinium, England, United Kingdom
    • ICL
      Londinium, England, United Kingdom
  • 1989-2003
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2001
    • University of Sussex
      Brighton, England, United Kingdom
    • University of Florence
      Florens, Tuscany, Italy
    • The Scripps Research Institute
      La Jolla, California, United States
  • 1998
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 1996
    • Gloucestershire Hospitals NHS Foundation Trust
      Gloucester, England, United Kingdom
  • 1995-1996
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 1979-1996
    • Case Western Reserve University
      • • School of Medicine
      • • Department of Physiology and Biophysics
      Cleveland, Ohio, United States
  • 1991-1995
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 1985-1992
    • Cleveland State University
      Cleveland, Ohio, United States
  • 1988
    • Loyola University Medical Center
      • Department of Medicine
      مايوود، إلينوي, Illinois, United States
  • 1982-1987
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 1984
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 1979-1984
    • Rutgers, The State University of New Jersey
      Нью-Брансуик, New Jersey, United States