Imperial College London

DrJonathanBaker

Faculty of MedicineNational Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7790jonathan.baker

 
 
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Location

 

223Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

46 results found

Wrench CL, Baker JR, Monkley S, Fenwick PS, Murray L, Donnelly LE, Barnes PJet al., 2023, Small airway fibroblasts from Chronic Obstructive Pulmonary Disease patients exhibit cellular senescence., Am J Physiol Lung Cell Mol Physiol

RATIONALE: Small airways disease (SAD) is a key early-stage pathology of chronic obstructive pulmonary disease (COPD). COPD is associated with cellular senescence whereby cells undergo growth arrest and express the senescence-associated secretory phenotype (SASP) leading to chronic inflammation and tissue remodelling. Parenchymal derived fibroblasts have been shown to display senescent properties in COPD, however small airway fibroblasts (SAF) have not been investigated. Therefore, this study investigated the role of these cells in COPD and their potential contribution to SAD. OBJECTIVES: To investigate the senescent and fibrotic phenotype of SAF in COPD. METHODS: SAF were isolated from non-smoker, smoker and COPD lung resection tissue (n=9-17). Senescence and fibrotic marker expression were determined using iCELLigence (proliferation), qPCR, Seahorse assay and ELISAs. COPD SAF were further enriched for senescent cells using FACSAria Fusion based on cell size and autofluorescence (10% largest/autofluorescent v 10% smallest/non-autofluorescent). The phenotype of the senescence-enriched population was investigated using RNA-sequencing and pathway analysis. MAIN RESULTS: Markers of senescence were observed in COPD SAF, including senescence-associated β-galactosidase, SASP release and reduced proliferation. Because the pathways driving this phenotype were unclear, we used cell-sorting to enrich for senescent COPD SAF. This population displayed increased p21CIP1 and p16INK4a expression and mitochondrial dysfunction. RNA-sequencing suggested these senescent cells express genes involved in oxidative stress response, fibrosis and mitochondrial dysfunction pathways. CONCLUSIONS: These data suggest COPD SAF are senescent and may be associated with fibrotic properties and mitochondrial dysfunction. Further understanding cellular senescence in SAF may lead to potential therapies to limit SAD progression.

Journal article

Ho V, Baker J, Willison K, Barnes P, Donnelly L, Klug Det al., 2023, Single cell quantification of microRNA from small numbers of non-invasively sampled primary human cells, Communications Biology, Vol: 6, Pages: 1-11, ISSN: 2399-3642

Expression levels of microRNAs (miRNAs) in single cells are low and conventional miRNA detection methods require amplification that can be complex, time-consuming, costly and may bias results. Single cell microfluidic platforms have been developed; however, current approaches are unable to absolutely quantify single miRNA molecules expressed in single cells. Herein, we present an amplification-free sandwich hybridisation assay to detect single miRNA molecules in single cells using a microfluidic platform that optically traps and lyses individual cells. Absolute quantification of miR-21 and miR-34a molecules was achieved at a single cell level in human cell lines and validated using real-time qPCR. The sensitivity of the assay was demonstrated by quantifying single miRNA molecules in nasal epithelial cells and CD3+ T-cells, as well as nasal fluid collected non-invasively from healthy individuals. This platform requires ~50 cells or ~30 µL biofluid and can be extended for other miRNA targets therefore it could monitor miRNA levels in disease progression or clinical studies.

Journal article

Ombredane HCJ, Fenwick PS, Barnes PJ, Bafadhel M, Ito K, Donnelly LE, Baker JRet al., 2023, Temporal Release of IL-1 Family Members from Virally Infected Airway Epithelial Cells Suggests IL-36γ Is the Early Responder, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 68, Pages: 339-341, ISSN: 1044-1549

Journal article

Fawzy A, Baker JR, Keller TL, Feemster LC, Donnelly LE, Hansel NNet al., 2022, Selected Bibliography of Recent Research in Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 206, Pages: 1408-1417, ISSN: 1073-449X

Journal article

Devulder J, Baker JR, Odqvist L, Donnelly LE, Barnes PJet al., 2022, Extracellular vesicles propagate cellular senescence by transferring miR34a in airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Hassibi S, Baker J, Barnes P, Donnelly Let al., 2022, COPD Monocyte-derived macrophages display hallmarks of senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Baker JR, Fenwick PS, Koss CK, Owles HB, Elkin SL, Fine JS, Thomas M, Kasmi KC, Barnes PJ, Donnelly LEet al., 2022, Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD, JCI Insight, Vol: 7, ISSN: 2379-3708

Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising new therapeutic strategy in the treatment of COPD.

Journal article

Wysoczanski R, Baker JR, Fenwick P, Alexandrov Y, Dunsby C, French P, Barnes PJ, Donnelly LEet al., 2022, Defective Phagocytosis in COPD Macrophages Is Improved by Mitochondrial Antioxidants Without Alteration in Mitochondrial Function, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Hassibi S, Baker JR, Barnes PJ, Donnelly LEet al., 2022, COPD Macrophages Show Reduced Clearance of Senescent Airway Epithelial Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Fenwick P, Baker JR, Koss CK, Ramirez F, Barnes PJ, El Kasmi KC, Donnelly LEet al., 2022, TRPV4 Identifies Phagocytic Macrophages and May Promote Phagocytosis in Both Healthy and COPD Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Ho V, Baker JR, Willison KR, Klug DR, Barnes PJ, Donnelly LEet al., 2022, Novel Single Cell Analysis of microRNA Levels in Response to Oxidative Stress and in COPD Using Microfluidic Technology, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Devulder J, Baker JR, Odqvist L, Donnelly LE, Barnes PJet al., 2022, Transfer of microRNA Through Extracellular Vesicles Propagate Airway Epithelial Cells Senescence in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Baker JR, Fenwick PS, Koss CK, Owles HB, El Kasmi KC, Barnes PJ, Donnelly LEet al., 2022, Inhibition of the IL-36 Receptor Reduces Viral Induced Cross-Talk Between Small Airway Epithelial Cells and Fibroblast in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Barnes PJ, Baker J, Donnelly LE, 2022, Autophagy in asthma and chronic obstructive pulmonary disease, CLINICAL SCIENCE, Vol: 136, Pages: 733-746, ISSN: 0143-5221

Journal article

Baker JR, Mahdi M, Nicolau DV, Ramakrishnan S, Barnes PJ, Simpson JL, Cass SP, Russell REK, Donnelly LE, Bafadhel Met al., 2022, Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis., The Lancet Respiratory Medicine, ISSN: 2213-2600

BACKGROUND: Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. METHODS: The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. These samples were used to investigate the evolution of inflammation in the early COVID-19 disease course and assess the effect of budesonide on inflammation. FINDINGS: 146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced in

Journal article

Koss CK, Wohnhaas CT, Baker JR, Tilp C, Przibilla M, Lerner C, Frey S, Keck M, Williams CMM, Peter D, Ramanujam M, Fine J, Gantner F, Thomas M, Barnes PJ, Donnelly LE, El Kasmi KCet al., 2021, IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice, Communications Biology, Vol: 4, Pages: 1-15, ISSN: 2399-3642

IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.

Journal article

Baker JR, Fenwick PS, Owles HB, Koss C, El-Kasmi K, Barnes PJ, Donnelly LEet al., 2021, IL-36? - a key mediator of neutrophilic inflammation in chronic obstructive pulmonary disease, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Devulder J, Baker JR, Donnelly LE, Barnes PJet al., 2021, Extracellular vesicles produced by airway epithelial cells in response to oxidative stress contain microRNAs associated with cellular senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Baker JR, Donnelly LE, 2021, Leukocyte function in COPD: clinical relevance and potential for drug therapy., The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 16, Pages: 2227-2242, ISSN: 1176-9106

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition affecting 10% of the global population over 45 years. Currently, there are no disease-modifying treatments, with current therapies treating only the symptoms of the disease. COPD is an inflammatory disease, with a high infiltration of leukocytes being found within the lung of COPD patients. These leukocytes, if not kept in check, damage the lung, leading to the pathophysiology associated with the disease. In this review, we focus on the main leukocytes found within the COPD lung, describing how the release of chemokines from the damaged epithelial lining recruits these cells into the lung. Once present, these cells become active and may be driven towards a more pro-inflammatory phenotype. These cells release their own subtypes of inflammatory mediators, growth factors and proteases which can all lead to airway remodeling, mucus hypersecretion and emphysema. Finally, we describe some of the current therapies and potential new targets that could be utilized to target aberrant leukocyte function in the COPD lung. Here, we focus on old therapies such as statins and corticosteroids, but also look at the emerging field of biologics describing those which have been tested in COPD already and potential new monoclonal antibodies which are under review.

Journal article

Ritchie AI, Baker JR, Parekh TM, Allinson JP, Bhatt SP, Donnelly LE, Donaldson GCet al., 2021, Update in Chronic Obstructive Pulmonary Disease 2020, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 14-22, ISSN: 1073-449X

Journal article

Ramakrishnan S, Nicolau D, Langford B, Mahdi M, Jeffers H, Mwasuku C, Krassowska K, Fox R, Binnian I, Glover V, Bright S, Butler C, Cane J, Halner A, Matthews P, Donnelly L, Simpson J, Baker J, Fadai N, Peterson S, Bengtsson T, Barnes P, Russell R, Bafadhel Met al., 2021, Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 763-772, ISSN: 2213-2600

Journal article

Kono Y, Colley T, To M, Papaioannou AI, Mercado N, Baker JR, To Y, Abe S, Haruki K, Ito K, Barnes PJet al., 2021, Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322

Journal article

Perez E, Baker JR, Di Giandomenico S, Kermani P, Parker J, Kim K, Yang J, Barnes PJ, Vaulont S, Scandura JM, Donnelly LE, Stout-Delgado H, Cloonan SMet al., 2020, Hepcidin Is Essential for Alveolar Macrophage Function and Is Disrupted by Smoke in a Murine Chronic Obstructive Pulmonary Disease Model, JOURNAL OF IMMUNOLOGY, Vol: 205, Pages: 2489-+, ISSN: 0022-1767

Journal article

Devulder J, Baker JR, Donnelly LE, Barnes PJet al., 2020, LSC-2020-Extracellular vesicles produced by bronchial epithelial cells in response to oxidative stress contain micro-RNAs associated with senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Wysoczanski R, Baker JR, Fenwick P, Garcia E, Kumar S, Neil MAA, Dunsby C, French PMW, Barnes PJ, Donnelly LEet al., 2020, Analysis of defective phagocytosis in COPD using super-resolution microscopy and automated bacterial quantification, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Baker JR, Fenwick PS, Donnelly L, Barnes PJ, Cloonan SMet al., 2020, Altered iron metabolism and elevated cellular senescence in COPD small airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Alter P, Baker JR, Dauletbaev N, Donnelly LE, Pistenmaa C, Schmeck B, Washko G, Vogelmeier CFet al., 2020, Update in Chronic Obstructive Pulmonary Disease 2019, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 348-355, ISSN: 1073-449X

Journal article

Fukuda Y, Akimoto K, Homma T, Baker JR, Ito K, Barnes PJ, Sagara Het al., 2020, Virus-Induced Asthma Exacerbations: SIRT1 Targeted Approach, JOURNAL OF CLINICAL MEDICINE, Vol: 9

Journal article

Baker JR, Donnelly LE, Barnes PJ, 2020, Senotherapy A New Horizon for COPD Therapy, CHEST, Vol: 158, Pages: 562-570, ISSN: 0012-3692

Journal article

Tsilogianni Z, Baker JR, Papaporfyriou A, Papaioannou AI, Papathanasiou E, Koulouris NG, Daly L, Ito K, Hillas G, Papiris S, Bakakos P, Loukides Set al., 2020, Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?, JOURNAL OF CLINICAL MEDICINE, Vol: 9

Journal article

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