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Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells (2016)
Journal Article
Poghosyan, A., Patel, J. K., Clifford, R. L., & Knox, A. J. (2016). Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells. Biochemical and Biophysical Research Communications, 476(4), 431-437. https://doi.org/10.1016/j.bbrc.2016.05.140

Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)?, nuclear factor (NF)-?B, and activ... Read More about Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells.

Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin ?v?6 expression (2016)
Journal Article
Tatler, A. L., Habgood, A., Porte, J., John, A. E., Stavrou, A., Hodge, E., …Jenkins, G. (2016). Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin αvβ6 expression. Journal of Biological Chemistry, 291(18), 9540-9553. https://doi.org/10.1074/jbc.M115.692368

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Active TGF?1 is considered central to the pathogenesis of IPF. A major mechanism of TGF?1 activation in the lung involves the epithelially restricted ?v?6... Read More about Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin ?v?6 expression.

A predictive computational framework for direct reprogramming between human cell types (2016)
Journal Article
Rackham, O. J. L., Firas, J., Fang, H., Oates, M. E., Holmes, M. L., Knaupp, A. S., …KNOX, A. (2016). A predictive computational framework for direct reprogramming between human cell types. Nature Genetics, 48(3), 331-335. https://doi.org/10.1038/ng.3487

Transdifferentiation, the process of converting from one cell type to another without going through a pluripotent state, has great promise for regenerative medicine. The identification of key transcription factors for reprogramming is currently limit... Read More about A predictive computational framework for direct reprogramming between human cell types.

Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial: Oral Glutamine Supplementation in Cystic Fibrosis (2015)
Journal Article
Forrester, D. L., Knox, A. J., Smyth, A. R., Barr, H. L., Simms, R., Pacey, S. J., …Fogarty, A. W. (2016). Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial: Oral Glutamine Supplementation in Cystic Fibrosis. Pediatric Pulmonology, 51(3), 253-257. https://doi.org/10.1002/ppul.23370

Rationale: Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that ora... Read More about Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial: Oral Glutamine Supplementation in Cystic Fibrosis.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort (2015)
Journal Article
Shaw, D. E., Sousa, A. R., Fowler, S. J., Fleming, L. J., Roberts, G., Corfield, J., …Chung, K. F. (2015). Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. European Respiratory Journal, 46(5), 1308-1321. https://doi.org/10.1183/13993003.00779-2015

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach. This c... Read More about Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

Adapting the electrospinning process to provide three unique environments for a tri-layered in vitro model of the airway wall (2015)
Journal Article
Bridge, J. C., Aylott, J. W., Brightling, C. E., Ghaemmaghami, A. M., Knox, A. J., Lewis, M. P., …Morris, G. E. (2015). Adapting the electrospinning process to provide three unique environments for a tri-layered in vitro model of the airway wall. Journal of Visualized Experiments, 101, Article e52986. https://doi.org/10.3791/52986

Electrospinning is a highly adaptable method producing porous 3D fibrous scaffolds that can be exploited in in vitro cell culture. Alterations to intrinsic parameters within the process allow a high degree of control over scaffold characteristics inc... Read More about Adapting the electrospinning process to provide three unique environments for a tri-layered in vitro model of the airway wall.

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.

Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. (2015)
Journal Article
John, M., Cockcroft, J. R., McKeever, T. M., Coward, W. R., Shale, D. J., Johnson, S. R., …Bolton, C. E. (2015). Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. International Journal of Chronic Obstructive Pulmonary Disease, 10(1), https://doi.org/10.2147/COPD.S76061

BACKGROUND: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the... Read More about Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial..

The statistical geometry of transcriptome divergence in cell-type evolution and cancer (2015)
Journal Article
Liang, C., Consortium, F., Forrest, A. R., & Wagner, G. ?. P. (2015). The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nature Communications, 6(1), https://doi.org/10.1038/ncomms7066

In evolution, body plan complexity increases due to an increase in the number ofindividualized cell types. Yet, there is very little understanding of the mechanisms thatproduce this form of organismal complexity. One model for the origin... Read More about The statistical geometry of transcriptome divergence in cell-type evolution and cancer.

Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis (2015)
Journal Article
Barr, H. L., Halliday, N., Cámara, M., Barrett, D. A., Williams, P., Forrester, D. L., …Fogarty, A. W. (2015). Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis. European Respiratory Journal, 46(4), 1046-1054. https://doi.org/10.1183/09031936.00225214

Copyright © ERS 2015. Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection. A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for... Read More about Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.

A novel electrospun biphasic scaffold provides optimal three-dimensional topography forin vitroco-culture of airway epithelial and fibroblast cells (2014)
Journal Article
Morris, G., Bridge, J., Brace, L., Knox, A., Aylott, J. W., Brightling, C., …Rose, F. R. (2014). A novel electrospun biphasic scaffold provides optimal three-dimensional topography forin vitroco-culture of airway epithelial and fibroblast cells. Biofabrication, 6(3), Article 035014. https://doi.org/10.1088/1758-5082/6/3/035014

Conventional airway in vitro models focus upon the function of individual structural cells cultured in a two-dimensional monolayer, with limited three-dimensional (3D) models of the bronchial mucosa. Electrospinning offers an attractive method to pro... Read More about A novel electrospun biphasic scaffold provides optimal three-dimensional topography forin vitroco-culture of airway epithelial and fibroblast cells.

A promoter-level mammalian expression atlas (2014)
Journal Article
Forrest, A. R., Kawaji, H., Rehli, M., Kenneth Baillie, J., de Hoon, M. J., Haberle, V., …Hayashizaki, Y. (2014). A promoter-level mammalian expression atlas. Nature, 507, 462-470. https://doi.org/10.1038/nature13182

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in... Read More about A promoter-level mammalian expression atlas.

A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis (2014)
Journal Article
Coward, W. R., Feghali-Bostwick, C. A., Jenkins, G., Knox, A. J., & Pang, L. (2014). A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis. FASEB Journal, 28(7), 3183-3196. https://doi.org/10.1096/fj.13-241760

Selective silencing of the cyclooxygenase-2 (COX-2) gene with the loss of the antifibrotic mediator PGE2 contributes to the fibrotic process in idiopathic pulmonary fibrosis (IPF). This study explored the role of G9a- and EZH2-mediated methylation of... Read More about A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis.

Immunocompetent 3D model of human upper airway for disease modeling and in vitro drug evaluation (2014)
Journal Article
Harrington, H., Cato, P., Salazar, F., Wilkinson, M., Knox, A., Haycock, J. W., …Ghaemmaghami, A. M. (2014). Immunocompetent 3D model of human upper airway for disease modeling and in vitro drug evaluation. Molecular Pharmaceutics, 11(7), 2082-2091. https://doi.org/10.1021/mp5000295

The development of more complex in vitro models for the assessment of novel drugs and chemicals is needed because of the limited biological relevance of animal models to humans as well as ethical considerations. Although some human-cell-based assays... Read More about Immunocompetent 3D model of human upper airway for disease modeling and in vitro drug evaluation.

Circulating antibody and memory B-cell responses to C. difficile toxins A and B in patients with C. difficile- associated diarrhoea, inflammatory bowel disease and cystic fibrosis (2013)
Journal Article
Monaghan, T. M., Robins, A., Knox, A., Sewell, H. F., & Mahida, Y. R. (2013). Circulating antibody and memory B-cell responses to C. difficile toxins A and B in patients with C. difficile- associated diarrhoea, inflammatory bowel disease and cystic fibrosis. PLoS ONE, 8(9), Article e74452. https://doi.org/10.1371/journal.pone.0074452

C. difficile infection (CDI) is rarely reported in cystic fibrosis (CF) patients despite frequent hospitalisations and antibiotic usage. Conversely, the prevalence of CDI in inflammatory bowel disease (IBD) has received increased attention. We inve... Read More about Circulating antibody and memory B-cell responses to C. difficile toxins A and B in patients with C. difficile- associated diarrhoea, inflammatory bowel disease and cystic fibrosis.

Abnormal Histone Methylation Is Responsible for Increased Vascular Endothelial Growth Factor 165a Secretion from Airway Smooth Muscle Cells in Asthma (2012)
Journal Article
Clifford, R. L., John, A. E., Brightling, C. E., & Knox, A. J. (2012). Abnormal Histone Methylation Is Responsible for Increased Vascular Endothelial Growth Factor 165a Secretion from Airway Smooth Muscle Cells in Asthma. Journal of Immunology, 189(2), 819-831. https://doi.org/10.4049/jimmunol.1103641

Vascular endothelial growth factor (VEGF), a key angiogenic molecule, is aberrantly expressed in several diseases including asthma where it contributes to bronchial vascular remodeling and chronic inflammation. Asthmatic human airway smooth muscle ce... Read More about Abnormal Histone Methylation Is Responsible for Increased Vascular Endothelial Growth Factor 165a Secretion from Airway Smooth Muscle Cells in Asthma.