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Clinical significance of Pseudomonas aeruginosa 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis (2019)
Journal Article
Webb, K., Fogarty, A., Barrett, D. A., Nash, E. F., Whitehouse, J. L., Smyth, A. R., …Cámara, M. (2019). Clinical significance of Pseudomonas aeruginosa 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis. Journal of Medical Microbiology, 68(12), 1823-1828. https://doi.org/10.1099/jmm.0.001099

Introduction : Pseudomonas aeruginosa is an important respiratory pathogen in cystic fibrosis (CF), which is associated with an accelerated decline in lung function, frequent pulmonary exacerbations and increased mortality. P. aeruginosa produces in... Read More about Clinical significance of Pseudomonas aeruginosa 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis.

Airway epithelial cell isolation techniques affect DNA methylation profiles with consequences for analysis of asthma related perturbations to DNA methylation (2019)
Journal Article
Clifford, R. L., Patel, J., MacIsaac, J. L., McEwen, L. M., Johnson, S. R., Shaw, D., …Kobor, M. S. (2019). Airway epithelial cell isolation techniques affect DNA methylation profiles with consequences for analysis of asthma related perturbations to DNA methylation. Scientific Reports, 9(1), 1-12. https://doi.org/10.1038/s41598-019-50873-y

The airway epithelium forms the interface between the inhaled environment and the lung. The airway epithelium is dysfunctional in asthma and epigenetic mechanisms are considered a contributory factor. We hypothesised that the DNA methylation profiles... Read More about Airway epithelial cell isolation techniques affect DNA methylation profiles with consequences for analysis of asthma related perturbations to DNA methylation.

Electrospun gelatin-based scaffolds as a novel 3D platform to study the function of contractile smooth muscle cells in vitro (2018)
Journal Article
Bridge, J. C., Amer, M. H., Morris, G. E., Martin, N., Player, D. J., Knox, A. J., …Rose, F. R. (2018). Electrospun gelatin-based scaffolds as a novel 3D platform to study the function of contractile smooth muscle cells in vitro. Biomedical Physics and Engineering Express, 4(4), Article 045039. https://doi.org/10.1088/2057-1976/aace8f

Contractile dysfunction of smooth muscle (SM) is a feature of chronic cardiovascular, respiratory and gastro-intestinal diseases. Owing to the low availability of human ex vivo tissue for the assessment of SM contractile function, the aim of this stu... Read More about Electrospun gelatin-based scaffolds as a novel 3D platform to study the function of contractile smooth muscle cells in vitro.

Suberanilohydroxamic acid prevents TGF-?1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation (2018)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2018). Suberanilohydroxamic acid prevents TGF-?1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1861(5), https://doi.org/10.1016/j.bbagrm.2018.03.007

Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE have been shown to contribute to the activation of lung fibroblasts and excessive deposition of col... Read More about Suberanilohydroxamic acid prevents TGF-?1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation.

Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD (2018)
Journal Article
Clifford, R. L., Fishbane, N., Patel, J., MacIsaac, J. L., McEwen, L. M., Fisher, A. J., …Knox, A. J. (2018). Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD. Clinical Epigenetics, 10(1), https://doi.org/10.1186/s13148-018-0464-5

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, i... Read More about Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD.

PINX1 and TERT are required for TNF-?-induced airway smooth muscle chemokine gene expression (2018)
Journal Article
Deacon, K., & Knox, A. J. (2018). PINX1 and TERT are required for TNF-?-induced airway smooth muscle chemokine gene expression. Journal of Immunology, 200(4), https://doi.org/10.4049/jimmunol.1700414

Airway smooth muscle (ASM) cells contribute to asthmatic lung pathology with chemokine hypersecretion and increased ASM cell mass. With little recent progress in the development of asthma therapies, a greater understanding of lung inflammation mechan... Read More about PINX1 and TERT are required for TNF-?-induced airway smooth muscle chemokine gene expression.

Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis (2017)
Journal Article
Coward, W. R., Brand, O. J., Pasini, A., Jenkins, G., Knox, A. J., & Pang, L. (in press). Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, https://doi.org/10.1165/rcmb.2017-0286OC

Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodelling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 re... Read More about Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis.

Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis (2017)
Journal Article
Barr, H. L., Cámara, M., Barrett, D., Williams, P., Forrester, D., Smyth, A., …Fogarty, A. W. (in press). Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis. ERJ Open Research, 3(3), https://doi.org/10.1183/23120541.00057-2017

Use of novel DNA methylation signatures to distinguish between human airway structural cell types (2017)
Conference Proceeding
Rajasekar, P., Clifford, R., MacIsaac, J., McEwen, L., Kobor, M., & Knox, A. (2017). Use of novel DNA methylation signatures to distinguish between human airway structural cell types.

INTRODUCTION: Chronic inflammatory and fibrotic lung diseases like asthma, COPD and pulmonary fibrosis are characterised by modified phenotype of the airway structural cells. Airway walls are comprised of a robust epithelial layer that lines the lume... Read More about Use of novel DNA methylation signatures to distinguish between human airway structural cell types.

Investigating genome wide DNA methylation in bronchial and lung fibroblasts from healthy individuals and individuals with COPD (2017)
Conference Proceeding
Clifford, R., Fishbane, N., Rajasekar, P., MacIsaac, J., McEwen, L., Fisher, A., …Hackett, T. (2017). Investigating genome wide DNA methylation in bronchial and lung fibroblasts from healthy individuals and individuals with COPD.

Rationale: Lung fibroblasts are implicated in respiratory disease pathology including chronic obstructive pulmonary disease (COPD). Phenotypic differences between fibroblasts isolated from the bronchi versus the lung parenchyma have been described bu... Read More about Investigating genome wide DNA methylation in bronchial and lung fibroblasts from healthy individuals and individuals with COPD.

The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma (2017)
Presentation / Conference
Kaczmarek, K. A., Clifford, R. L., Patel, J. K., Shaw, D., Dowden, J., & Knox, A. J. (2017, May). The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma. Poster presented at American Thoracic Society 2017 International Conference

Introduction and objectives: Asthma is estimated to affect at least 300 million people globally. About 25% of the patients do not respond to therapy; therefore we need to develop novel treatments. ASM cells have a crucial role in asthma, contributin... Read More about The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma.

Role of ROCK isoforms in regulation of stiffness induced myofibroblast differentiation in lung fibrosis (2017)
Journal Article
Htwe, S. S., Cha, B. H., Yue, K., Khademhosseini, A., Knox, A. J., & Ghaemmaghami, A. M. (2017). Role of ROCK isoforms in regulation of stiffness induced myofibroblast differentiation in lung fibrosis. American Journal of Respiratory Cell and Molecular Biology, 56(6), 772-783. https://doi.org/10.1165/rcmb.2016-0306OC

Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibroti... Read More about Role of ROCK isoforms in regulation of stiffness induced myofibroblast differentiation in lung fibrosis.

sTREM-1 is elevated in cystic fibrosis and correlates with proteases (2017)
Journal Article
Forrester, D., Barr, H. L., Fogarty, A., & Knox, A. (2017). sTREM-1 is elevated in cystic fibrosis and correlates with proteases. Pediatric Pulmonology, 52(4), 467-471. https://doi.org/10.1002/ppul.23650

Background: sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) is a novel inflammatory marker that may be of clinical use in cystic fibrosis (CF). Dysregulation of the TREM pathway has been demonstrated in other inflammatory diseases... Read More about sTREM-1 is elevated in cystic fibrosis and correlates with proteases.

Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis (2016)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2016). Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis. Thorax, 71(Supp3), Article A32. https://doi.org/10.1136/thoraxjnl-2016-209333.59

Introduction and objectives: Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth fac... Read More about Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis.

Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis (2016)
Journal Article
Pasini, A., Brand, O. J., Jenkins, G., Knox, A. J., & Pang, L. (2016). Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis. Thorax, 71(Suppl. 3), A32. https://doi.org/10.1136/thoraxjnl-2016-209333.59

Introduction and objectives: Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth fac... Read More about Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis.

S133?Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd (2016)
Journal Article
Clifford, R. L., Fishbane, N., Rajasekar, P., Fisher, A., Kobor, M., Knox, A., & Hackett, T. (2016). S133?Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd. Thorax, 71(Suppl 3), Article A79.1-A79. https://doi.org/10.1136/thoraxjnl-2016-209333.139

Rationale: Lung fibroblasts are implicated in respiratory disease pathology including chronic obstructive pulmonary disease (COPD). Phenotypic differences between fibroblasts isolated from the airway versus the parenchyma have been described but no s... Read More about S133?Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd.

Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor ?1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis (2016)
Journal Article
Brand, O. J., Pasini, A., Habgood, A., Knox, A. J., Jenkins, G., & Pang, L. (2016). Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor ?1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis. Thorax, 71(Suppl. 3), A31. https://doi.org/10.1136/thoraxjnl-2016-209333.58

Introduction and Objectives: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that is refractory to current treatment options. Transforming growth factor (TGF)-β1 is a key pro-fibrotic cytokine that plays a cruc... Read More about Suberanilohydroxamic acid (SAHA) inhibits collagen deposition in a transforming growth factor ?1-driven precision cut lung slice (PCLS) model of pulmonary fibrosis.

P238?Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors (2016)
Journal Article
Clifford, R. L., Patel, J., Shaw, D., Knox, A., & Kobor, M. (2016). P238?Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors. Thorax, 71(Suppl 3), A215.2-A216. https://doi.org/10.1136/thoraxjnl-2016-209333.381

Rationale: Genetic mechanisms fail to fully explain asthma pathogenesis and environmental factors are considered to play an important role. Environmental factors may lead to permanent changes in epigenetic patterns and contribute to asthma. Epigeneti... Read More about P238?Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors.

The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma (2016)
Journal Article
Kaczmarek, K., Clifford, R. L., Patel, J., Shaw, D., Dowden, J., & Knox, A. (2016). The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma. Thorax, 71(Suppl3), A214-A215. https://doi.org/10.1136/thoraxjnl-2016-209333.379

Introduction and objectives: Asthma is estimated to affect at least 300 million people globally. About 25% of the patients do not respond to therapy; therefore we need to develop novel treatments. ASM cells have a crucial role in asthma, contributing... Read More about The role of histone arginine methylation in gene expression of airway smooth muscle cells in asthma.

Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema (2016)
Journal Article
John, A. E., Wilson, M. R., Habgood, A., Porte, J., Tatler, A. L., Stavrou, A., …Jenkins, R. G. (2016). Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema. Science Signaling, 9(451), Article ra104. https://doi.org/10.1126/scisignal.aad5568

Heterotrimeric guanine nucleotide–binding protein (G protein) signaling is a ubiquitous signaling system that links hundreds of G protein–coupled receptors (GPCRs) with four G protein signaling pathways. Two of these pathways, one mediated by Gq and... Read More about Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema.