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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.

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), doi: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.

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.

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. (in press). Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd. Thorax, 71(Suppl3), doi: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 Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd.

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. (in press). Investigating genome wide dna methylation in airway smooth muscle cells from asthmatic and non-asthmatic donors. Thorax, 71(Suppl3), doi: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 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. doi: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.

Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation (2016)
Journal Article
Clifford, R. L., Jones, M. J., MacIsaac, J. L., McEwen, L. M., Goodman, S. J., Mostafavi, S., …Carlsten, C. (2017). Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. Journal of Allergy and Clinical Immunology, 139(1), doi:10.1016/j.jaci.2016.03.046

Background Allergic disease affects 30% to 40% of the world's population, and its development is determined by the interplay between environmental and inherited factors. Air pollution, primarily consisting of diesel exhaust emissions, has increase... Read More about Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation.

CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET (2015)
Journal Article
Clifford, R. L., Patel, J. K., John, A. E., Tatler, A. L., Mazengarb, L., Brightling, C. E., & Knox, A. J. (2015). CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET. AJP - Lung Cellular and Molecular Physiology, 308(9), L962-L972. https://doi.org/10.1152/ajplung.00021.2015

© 2015 The American Physiological Society. Asthma is characterized by airway inflammation and remodeling and CXCL8 is a CXC chemokine that drives steroid-resistant neutrophilic airway inflammation. We have shown that airway smooth muscle (ASM) cells... Read More about CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET.

Epigenetics and miRNA emerge as key regulators of smooth muscle cell phenotype and function (2012)
Journal Article
Clifford, R. L., Singer, C. A., & John, A. E. (2013). Epigenetics and miRNA emerge as key regulators of smooth muscle cell phenotype and function. Pulmonary Pharmacology and Therapeutics, 26(1), 75-85. https://doi.org/10.1016/j.pupt.2012.07.002

Regulation of phenotypic plasticity in smooth muscle requires an understanding of the mechanisms regulating phenotype-specific genes and the processes dysregulated during pathogenesis. Decades of study in airway smooth muscle has provided extensive k... Read More about Epigenetics and miRNA emerge as key regulators of smooth muscle cell phenotype and function.

TNF and IFN  Synergistically Enhance Transcriptional Activation of CXCL10 in Human Airway Smooth Muscle Cells via STAT-1, NF- B, and the Transcriptional Coactivator CREB-binding Protein (2010)
Journal Article
Clarke, D. L., Clifford, R. L., Jindarat, S., Proud, D., Pang, L., Belvisi, M., & Knox, A. J. (2010). TNF and IFN  Synergistically Enhance Transcriptional Activation of CXCL10 in Human Airway Smooth Muscle Cells via STAT-1, NF- B, and the Transcriptional Coactivator CREB-binding Protein. Journal of Biological Chemistry, 285(38), 29101-29110. https://doi.org/10.1074/jbc.m109.0999952

Asthmatic airway smooth muscle (ASM) expresses interferon-γ-inducible protein-10 (CXCL10), a chemokine known to mediate mast cell migration into ASM bundles that has been reported in the airways of asthmatic patients. CXCL10 is elevated in patients s... Read More about TNF and IFN  Synergistically Enhance Transcriptional Activation of CXCL10 in Human Airway Smooth Muscle Cells via STAT-1, NF- B, and the Transcriptional Coactivator CREB-binding Protein.

Vitamin D - a new treatment for airway remodelling in asthma? (2009)
Journal Article
Clifford, R. L., & Knox, A. J. (2009). Vitamin D - a new treatment for airway remodelling in asthma?. British Journal of Pharmacology, 158(6), 1426-1428. https://doi.org/10.1111/j.1476-5381.2009.00429.x

Increased airway smooth muscle (ASM) mass plays a critical role in chronic asthmatic airway remodelling. ASM cell hypertrophy and hyperplasia are likely to contribute to increased ASM mass and a variety of mitogens induce ASM proliferation in cell cu... Read More about Vitamin D - a new treatment for airway remodelling in asthma?.

Novel Regulation of Vascular Endothelial Growth Factor-A (VEGF-A) by Transforming Growth Factor β1: REQUIREMENT FOR Smads,β-CATENIN, AND GSK3β (2008)
Journal Article
Clifford, R. L., Deacon, K., & Knox, A. J. (2008). Novel Regulation of Vascular Endothelial Growth Factor-A (VEGF-A) by Transforming Growth Factor β1: REQUIREMENT FOR Smads,β-CATENIN, AND GSK3β. Journal of Biological Chemistry, 283(51), 35337-35353. https://doi.org/10.1074/jbc.m803342200

Vascular endothelial growth factor (VEGF) is a vital angiogenic effector, regulating key angiogenic processes. Vascular development relies on numerous signaling pathways, of which those induced by transforming growth factor-β (TGFβ) are critical. The... Read More about Novel Regulation of Vascular Endothelial Growth Factor-A (VEGF-A) by Transforming Growth Factor β1: REQUIREMENT FOR Smads,β-CATENIN, AND GSK3β.