Martin Clynes

Dublin City University, Dublin, Leinster, Ireland

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Publications (228)654.9 Total impact

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    ABSTRACT: Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity.
    BMC genomics. 10/2014; 15(1):904.
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    ABSTRACT: Purpose: A role for a bacterium, Bacillus oleronius, originally isolated from a Demodex mite in the induction of ocular rosacea has been proposed. The aim of this work was to characterize the response of a corneal epithelial cell line to Bacillus proteins as this might give an insight into how such proteins contribute to the symptoms of ocular rosacea in vivo. Methods: The effect of exposing Bacillus protein preparation on hTCEpi cells was measured by monitoring changes in cell proliferation and the expression of a number of genes associated with inflammation. The production of inflammatory cytokines was measured and the expression and activity of MMP-9 was quantified. Results: Exposure of corneal epithelial cells (hTCEpi) to 2 or 6 µg/mL Bacillus protein resulted in a dose dependent reduction in cell proliferation. Exposure of cells to 6 µg/mL Bacillus protein did not induce apoptosis but there was an increase in the expression of genes coding for IL-6 (13.8-fold), IL-1β (4.0-fold), IL-8 (11.1-fold) and TNF-α (4.1-fold). Increased expression of genes coding for the defensins, CCL20 (4.5-fold) and S100A7 (6.8-fold) was also observed. Elevated production of IL-6 and IL-8 was evident from cells exposed to 2 and 6 μg/mL Bacillus protein. hTCEpi cells demonstrated increased MMP-9 expression (3.2-fold, p = 0.003) and activity (2.2-fold, p = 0.0186) after 48 hours exposure to 6 µg/mL Bacillus protein preparation. Conclusions: The results suggest that interaction of Demodex-associated Bacillus proteins with the corneal surface could lead to tissue degradation and inflammation possibly leading to corneal scarring.
    Investigative ophthalmology & visual science. 10/2014;
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    ABSTRACT: Purpose: The improved surgical outcomes associated with cultivated amniotic membrane expanded limbal epithelial (AMLE) grafts compared to donor transplant methods have led to significant adoption of this technique for treatment of limbal stem cell deficiency. The molecular basis for the superior clinical performance of these grafts remains unclear. In this study, we compare the transcriptomes of AMLE and donor central corneal epithelium (CE) to investigate differential gene expression between these tissue types. Methods: The mRNA expression profiles of AMLE and CE were assayed using microarrays. Transcripts with a 1.5 fold change in either direction in addition to a Bonferroni adjusted p-value < 0.05 were considered to be differentially expressed. Expression changes detected by microarray profiling and important corneal-limbal markers were assessed using quantitative real-time PCR (qRT-PCR) and immunofluorescence staining. Results: 487 probesets (319 upregulated & 168 downregulated) were found to be differentially expressed between AMLE and CE. Enrichment analysis revealed significant overrepresentation of multiple biological processes (e.g. response to wounding, wound-healing and regulation of cell morphogenesis) within the differentially expressed gene-list. The expression of a number of genes that were upregulated (ABCG2, S100A9, ITGA5, TIMP2, FGF5, PDGFC, SEMA3A) and downregulated (KLF4, P63α) in AMLE were confirmed using qRT-PCR. Immunofluorescence confirmed that AMLE cultures were P63α, ABCG2, CK3, CK12 and E-cadherin (E-cad) positive. Conclusions: In this study we have shown that genes associated with wound healing processes are upregulated in AMLE. These gene expression changes may contribute to corneal restoration and the positive outcomes associated with transplantation.
    Investigative ophthalmology & visual science 08/2014; · 3.43 Impact Factor
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    ABSTRACT: HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling.
    Molecular cancer. 06/2014; 13(1):157.
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    ABSTRACT: Studies have endeavoured to reconcile whether dysfunction of neutrophils in people with cystic fibrosis (CF) is as a result of the genetic defect or secondary due to infection and inflammation. In this study we illustrate that disrupted function of the CF transmembrane conductance regulator (CFTR), such as that which occurs in patients with ΔF508 and/or G551D mutations, correlates with impaired degranulation of antimicrobial proteins. We demonstrate that CF blood neutrophils release less secondary and tertiary granule components compared to control cells and that activation of the low-molecular-mass GTP-binding protein Rab27a, involved in the regulation of granule trafficking, is defective. The mechanism leading to impaired degranulation involves altered ion homeostasis caused by defective CFTR function with increased cytosolic levels of chloride and sodium, yet decreased magnesium measured in CF neutrophils. Decreased magnesium concentration in vivo and in vitro resulted in significantly decreased levels of GTP-bound Rab27a. Treatment of G551D patients with the ion channel potentiator ivacaftor, resulted in normalized neutrophil cytosolic ion levels and activation of Rab27a thereby leading to increased degranulation and bacterial killing. Our results confirm that intrinsic alterations of circulating neutrophils from patients with CF are corrected by ivacaftor thus illustrating additional clinical benefits for CFTR modulator therapy.
    Blood 06/2014; · 9.78 Impact Factor
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    ABSTRACT: Identification of protein targets, which play a role in breast cancer invasion may help in understanding the rapid progression of cancer and may lead to the development of new biomarkers for the disease. In this study, we have compared two highly invasive and two poorly invasive breast cancer cell lines using comparative label-free LC-MS profiling in order to identify differentially expressed proteins that may be linked to the invasive phenotype in vitro. Forty-five proteins were found to be up-regulated and 34 proteins to be down-regulated respectively. UV excision repair protein RAD23 homologue B (RAD23B) was found amongst the down-regulated proteins in highly invasive breast cancer cell lines. In poorly invasive breast cancer cell lines, siRNA mediated down-regulation of RAD23B subsequently led to an increase in invasion and adhesion in vitro. Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed that a high percentage (>80%) of RAD23B positive nuclei was significantly associated with histopathological grade 1 and 2 breast cancers and with low mitotic activity. In addition, a high staining intensity for RAD23B in the cytoplasm was significantly associated with histopathological grade 3 breast cancers. This study suggests a potential role of RAD23B in breast cancer progression and may further imply a tumour suppressor role of nuclear RAD23B in breast cancer.
    Journal of Proteome Research 06/2014; · 5.06 Impact Factor
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    ABSTRACT: While the long-term physiological adaptation of the neuromuscular system to changed functional demands is usually reflected by unilateral skeletal muscle transitions, the progressive degeneration of distinct motor neuron populations is often associated with more complex changes in the abundance and/or isoform expression pattern of contractile proteins and metabolic enzymes. In order to evaluate these intricate effects of primary motor neuronopathy on the skeletal muscle proteome, label-free mass spectrometry was employed to study global alterations in the wobbler mouse model of progressive neurodegeneration. In motor neuron disease, fibre type specification and the metabolic weighting of bioenergetic pathways appear to be strongly influenced by both a differing degree of a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fibre type shifting. Proteomic profiling confirmed this pathobiochemical complexity of disease-induced changes and showed distinct alterations in 72 protein species, including a variety of fibre type-specific isoforms of contractile proteins, metabolic enzymes, metabolite transporters and ion-regulatory proteins, as well as changes in molecular chaperones and various structural proteins. Increases in slow myosin light chains and the troponin complex and a decrease in fast myosin binding protein probably reflect the initial preferential loss of the fast type of neuromuscular synapses in motor neuron disease.
    Bioscience Reports 06/2014; · 1.88 Impact Factor
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    ABSTRACT: Development of more effective therapeutic strategies for cancers of high unmet need requires the continued discovery of disease-specific protein targets for therapeutic antibody targeting. In order to identify novel proteins associated with cancer cell invasion/metastasis, we present here an alternative to antibody targeting of cell surface proteins with an established role in invasion; our functional antibody screening approach involves the isolation and selection of MAbs that are primarily screened for their ability to inhibit tumour invasion. A clonal population of the Mia PaCa-2, a pancreatic ductal adenocarcinoma (PDAC) cell line, which displays a highly invasive phenotype, was used to generate MAbs with the objective of identifying membrane targets directly involved in cancer invasion. Selected MAb 7B7 can significantly reduce invasion in a dose-responsive manner in Mia PaCa-2 clone 3 and DLKP-M squamous lung carcinoma cells. Using immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis, the target antigen of anti-invasive antibody, 7B7, was determined to be the heterodimeric Ku antigen, Ku70/80, a core protein composed of the Ku70 and Ku80 subunits which is involved in non-homologous end-joining (NHEJ) DNA repair. RNA interference-mediated knockdown of Ku70 and Ku80 resulted in a marked decrease in the invasive capacity of Mia PaCa-2 clone 3 and DLKP-M cells, indicating that Ku70/Ku80 is functionally involved in pancreatic and lung cancer invasion. Immunohistochemical analysis demonstrated Ku70/Ku80 immunoreactivity in 37 PDAC tumours, indicating that this heterodimer is highly expressed in this aggressive cancer type. This study demonstrates that a functional MAb screening approach coupled with immunoprecipitation/proteomic analyses can be successfully applied to identify functional anti-invasive MAbs and potential novel targets for therapeutic antibody targeting.
    Tumor Biology 04/2014; · 2.52 Impact Factor
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    ABSTRACT: Background Serum profiling using mass spectrometry-based proteomic techniques has great potential to detect biomarkers that might improve the management for advanced breast cancer patients. The albuminome has previously been investigated as a tool in biomarker discovery, however other high abundant blood proteins are also likely to sequester potentially interesting molecules. Methods Affinity resin purified and isolated Transferrin and associated bound proteins from normal control and breast cancer patient serum samples were analysed by label-free mass spectrometry during the discovery phase. Results 21 significant proteins were identified with Fibrinogen and Fibronectin selected for further analysis in an independent sample set, with significant difference found when comparing the controls groups (normal healthy control, inflammatory bowel disease and benign breast disease) to stage IV breast cancer. Conclusions The area under the curve value for Fibrinogen compared favourably with cancer antigen 15-3, an established breast cancer tumour marker. A combination of all three biomarkers improved accuracy when comparing control/benign to stage V breast cancer patient groups. General Significance Mass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence.
    BBA Clinical. 01/2014;
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    ABSTRACT: The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance.
    Frontiers in Oncology 01/2014; 4:40.
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    ABSTRACT: Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.
    Cancer Growth and Metastasis 01/2014; 7:33-42.
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    ABSTRACT: Alpha-1 antitrypsin (AAT) is the major physiological inhibitor of a range of serine proteases, and in the lung, it maintains a protease-antiprotease balance. AAT deficiency (AATD) is an autosomal co-dominant condition with the Z mutation being the most common cause. Individuals homozygous for Z (PiZZ) have low levels of circulating mutant Z-AAT protein leading to premature emphysematous lung disease. Extensive glycoanalysis has been performed on normal AAT (M-AAT) from healthy individuals and the importance of glycosylation in affecting the immune modulatory roles of AAT is documented. However, no glycoanalysis has been carried out on Z-AAT from deficient individuals to date. In this study, we investigate whether the glycans present on Z-AAT differ to those found on M-AAT from healthy controls. Plasma AAT was purified from 10 individuals: 5 AATD donors with the PiZZ phenotype and 5 PiMM healthy controls. Glycoanalysis was performed employing N-glycan release, exoglycosidase digestion and UPLC analysis. No difference in branched glycans was identified between AATD and healthy controls. However, a significant increase in both outer arm (α1-3) (p = 0.04) and core (α1-6) fucosylated glycans (p < 0.0001) was found on Z-AAT compared to M-AAT. This study has identified increased fucosylation on N-glycans of Z-AAT indicative of ongoing inflammation in AATD individuals with implications for early therapeutic intervention.
    Journal of Proteome Research 12/2013; · 5.06 Impact Factor
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    ABSTRACT: Improving the efficiency of recombinant protein production by CHO cells is highly desirable as more complex proteins (MAbs, fusion proteins, blood/clotting factors, etc.) go into development and come onto the market. Previous reports have shown that miRNA-7 overexpression arrests the growth of CHO cells and that its depletion increases the proliferation of various cell types. In this study we generated stable CHO clones that overexpressed a miR-7-specific decoy transcript (sponge) downstream of a GFP reporter gene. The miR-7 sponge efficiently diverted miR-7 away from its endogenous targets as exemplified by the increased expression of CDC7. Although the sponge effectively sequestered miR-7, it also appeared to protect the bound miRNA sequence from degradation in the cell, as exemplified by the apparent increase in mature miR-7 levels without any change in primary transcription. Phenotypically, CHO clones with sequestered miR-7 displayed improved maximum cell density (40%), significantly improved viability and an almost 2-fold increase in yield of secreted protein in a fed-batch culture. These findings demonstrate that miRNA sponge transcripts could potentially be used in cell line development projects to generate producer clones that grow to higher densities and last longer in the bioreactor - thereby improving product yield.
    Biotechnology Journal 10/2013; · 3.71 Impact Factor
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    ABSTRACT: Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.
    Experimental Eye Research 09/2013; · 3.03 Impact Factor
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    ABSTRACT: Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, namely luminal A, luminal B, HER2, normal-like and basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis. Indeed, it is important to identify patients at risk of developing aggressive disease so as to tailor the level of clinical intervention. We have developed a user-friendly, web-based system to allow the evaluation of genes/microRNAs (miRNAs) that are significantly associated with survival in breast cancer and its molecular subtypes. The algorithm combines gene expression data from multiple microarray experiments which frequently also contain miRNA expression information, and detailed clinical data to correlate outcome with gene/miRNA expression levels. This algorithm integrates gene expression and survival data from 26 datasets on 12 different microarray platforms corresponding to approximately 17,000 genes in up to 4,738 samples. In addition, the prognostic potential of 341 miRNAs can be analysed. We demonstrated the robustness of our approach in comparison to two commercially available prognostic tests, oncotype DX and MammaPrint. Our algorithm complements these prognostic tests and is consistent with their findings. In addition, BreastMark can act as a powerful reductionist approach to these more complex gene signatures, eliminating superfluous genes, potentially reducing the cost and complexity of these multi-index assays. Known miRNA prognostic markers, mir-205 and mir-93, were used to confirm the prognostic value of this tool in a miRNA setting. We also applied the algorithm to examine expression of 58 receptor tyrosine kinases in the basal-like subtype, identifying six receptor tyrosine kinases associated with poor disease-free survival and/or overall survival (EPHA5, FGFR1, FGFR3, VEGFR1, PDGFRbeta, and TIE1). A web application for using this algorithm is currently available at http://glados.ucd.ie/BreastMark/index.html. BreastMark is a powerful tool for examining putative gene/miRNA prognostic markers in breast cancer. The value of this tool will be in the preliminary assessment of putative biomarkers in breast cancer. It will be of particular use to research groups with limited bioinformatics facilities.
    Breast cancer research: BCR 07/2013; 15(4):R52. · 5.87 Impact Factor
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    ABSTRACT: Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.
    Molecular Cancer 07/2013; 12(1):69. · 5.13 Impact Factor
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    ABSTRACT: Weighted gene coexpression network analysis (WGCNA) is a powerful "guilt-by-association" based method to extract coexpressed groups of genes from large heterogeneous mRNA expression datasets. We have utilised WGCNA to identify 11 corregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.g. tumour grade), survival endpoints for breast cancer as a whole (disease free survival (DFS), distant disease free survival (DDFS) and overall survival (OS)) and also its molecular subtypes (luminal A, luminal B, HER2+ and basal-like). Examples of findings arising from this work include the identification of a cluster of proliferation-related genes, that when upregulated correlated to increased tumour grade and were associated with poor survival in general. The prognostic potential of novel genes e.g. ubiquitin-conjugating enzyme E2S (UBE2S) within this group were confirmed in an independent dataset. In addition, gene clusters were also associated with survival for breast cancer molecular subtypes including a cluster of genes that was found to correlate with prognosis exclusively for basal-like breast cancer. The upregulation of several single genes within this coexpression cluster e.g. the potassium channel, subfamily K, member 5 (KCNK5) were associated with poor outcome for the basal-like molecular subtype. We have developed an online database to allow user friendly access to the coexpression patterns and the survival analysis outputs uncovered in this study (Availability: http://glados.ucd.ie/Coexpression/).
    Carcinogenesis 06/2013; · 5.64 Impact Factor
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    ABSTRACT: The majority of patients afflicted with Duchenne muscular dystrophy develop cardiomyopathic complications, warranting large-scale proteomic studies of global cardiac changes for the identification of new protein markers of dystrophinopathy. The aged heart from the X-linked dystrophic mdx mouse has been shown to exhibit distinct pathological aspects of cardiomyopathy. In order to establish age-related alterations in the proteome of dystrophin-deficient hearts, cardiomyopathic tissue from young versus aged mdx mice was examined by label-free LC-MS/MS. Significant age-dependent alterations were established for 67 proteins, of which 28 proteins were shown to exhibit a lower abundance and 39 proteins were found to be increased in their expression levels. Drastic changes were demonstrated for 17 proteins, including increases in immunoglobulin chains and transferrin, and drastic decreases in laminin, nidogen and annexin. An immunblotting survey of young and old wild type versus mdx hearts confirmed these proteomic findings and illustrated the effects of natural aging versus dystrophin deficiency. These proteome-wide alterations suggest a disintegration of the basal lamina structure and cytoskeletal network in dystrophin-deficient cardiac fibres, increased levels of antibodies in a potential autoimmune reaction of the degenerating heart, compensatory binding of excess iron and a general perturbance of metabolic pathways in dystrophy-associated cardiomyopathy. This article is protected by copyright. All rights reserved.
    Proteomics 05/2013; · 4.43 Impact Factor
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    ABSTRACT: The selection of clones displaying a high rate of cell growth is an essential component of Chinese hamster ovary (CHO) cell line development. In recent years various "omics" technologies have been utilised to understand the mechanisms underlying bioprocess phenotypes. In this study, gene expression analysis using a CHO-specific microarray was conducted for a panel of CHO-K1 MAb-secreting cell lines spanning a range of growth rates that were derived from a single cell line development project. In-silico functional analysis of the resulting transcriptomic data revealed the overrepresentation of biological processes such as cell cycle and translation within those genes upregulated during fast growth, while genes associated with cellular homeostasis were downregulated. Using differential expression and correlation analysis we identified a high priority group of 416 transcripts (190 upregulated; 226 downregulated) associated with growth rate. Expression changes of eight of these genes were independently confirmed by qPCR. Finally, we demonstrate the enrichment of predicted mRNA targets of miR17-92, a microRNA (miRNA) cluster known to be upregulated during rapid proliferation, within downregulated transcripts.
    Journal of Biotechnology 05/2013; · 3.18 Impact Factor

Publication Stats

3k Citations
654.90 Total Impact Points

Institutions

  • 1990–2014
    • Dublin City University
      • • National Institute for Cellular Biotechnology (NICB)
      • • School of Nursing and Human Sciences
      • • National Institute for Cellular Biology
      Dublin, Leinster, Ireland
  • 2013
    • Royal College of Surgeons in Ireland
      Dublin, Leinster, Ireland
  • 2004–2012
    • Dublin Institute of Technology
      Dublin, Leinster, Ireland
    • Charles University in Prague
      • Farmaceutická fakulta v Hradci Králové
      Praha, Hlavni mesto Praha, Czech Republic
  • 2010–2011
    • Beaumont Hospital
      Dublin, Leinster, Ireland
    • Trinity College Dublin
      • School of Pharmacy and Pharmaceutical Sciences
      Dublin, L, Ireland
  • 2008
    • St Vincent's University Hospital
      Dublin, Leinster, Ireland
  • 2005–2006
    • National University of Ireland, Maynooth
      • • Department of Biology
      • • Department of Chemistry
      Maynooth, L, Ireland
  • 2003
    • Royal Victoria Eye and Ear Hospital
      Dublin, Leinster, Ireland