2024 |
Gomez HM, Haw TJ, Ilic D, Robinson P, Donovan C, Croft AJ, et al., 'Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma', Journal of Allergy and Clinical Immunology, (2024)
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2023 |
Tu X, Gomez HM, Kim RY, Brown AC, de Jong E, Galvao I, et al., 'Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma', Respiratory Research, 24 (2023) [C1]
Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma... [more]
Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma in disease pathogenesis may expedite the development of novel targeted treatment strategies. In this study, we performed transcriptomics on the airway and parenchyma using a house dust mite (HDM)-induced model of experimental asthma that replicates key features of the human disease. HDM exposure increased the expression of 3,255 genes, of which 212 were uniquely increased in the airways, 856 uniquely increased in the parenchyma, and 2187 commonly increased in both compartments. Further interrogation of these genes using a combination of network and transcription factor enrichment analyses identified several transcription factors that regulate airway and/or parenchymal gene expression, including transcription factor EC (TFEC), transcription factor PU.1 (SPI1), H2.0-like homeobox (HLX), metal response element binding transcription factor-1 (MTF1) and E74-like factor 4 (ets domain transcription factor, ELF4) involved in controlling innate immune responses. We next assessed the effects of inhibiting lung SPI1 responses using commercially available DB1976 and DB2313 on key disease outcomes. We found that both compounds had no protective effects on airway inflammation, however DB2313 (8¿mg/kg) decreased mucus secreting cell number, and both DB2313 (1¿mg/kg) and DB1976 (2.5¿mg/kg and 1¿mg/kg) reduced small airway collagen deposition. Significantly, both compounds decreased airway hyperresponsiveness. This study demonstrates that SPI1 is important in HDM-induced experimental asthma and that its pharmacological inhibition reduces HDM-induced airway collagen deposition and hyperresponsiveness.
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Nova |
2023 |
Vanders RL, Gomez HM, Hsu AC, Daly K, Wark PAB, Horvat JC, Hansbro PM, 'Inflammatory and antiviral responses to influenza A virus infection are dysregulated in pregnant mice with allergic airway disease.', Am J Physiol Lung Cell Mol Physiol, 325 L385-L398 (2023) [C1]
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Nova |
2023 |
Liu G, Haw TJ, Starkey MR, Philp AM, Pavlidis S, Nalkurthi C, et al., 'TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.', Nat Commun, 14 7349 (2023) [C1]
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Nova |
2022 |
Donovan C, Kim RY, Galvao I, Jarnicki AG, Brown AC, Jones-Freeman B, et al., 'Aim2 suppresses cigarette smoke-induced neutrophil recruitment, neutrophil caspase-1 activation and anti-Ly6G-mediated neutrophil depletion', IMMUNOLOGY AND CELL BIOLOGY, 100 235-249 (2022) [C1]
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Nova |
2022 |
Vanka KS, Shukla S, Gomez HM, James C, Palanisami T, Williams K, et al., 'Understanding the pathogenesis of occupational coal and silica dust-associated lung disease', EUROPEAN RESPIRATORY REVIEW, 31 (2022) [C1]
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Nova |
2022 |
Tu X, Kim RY, Brown AC, de Jong E, Jones-Freeman B, Ali MK, et al., 'Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap', Journal of Allergy and Clinical Immunology, 150 817-829.e6 (2022) [C1]
Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COP... [more]
Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied. Objectives: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure. Methods: Female BALB/c mice were chronically exposed to house dust mite antigen for 11 weeks to induce experimental asthma, cigarette smoke for 8 weeks to induce experimental COPD, or both concurrently to induce experimental ACO. Lung inflammation, structural changes, and lung function were assessed. RNA-sequencing was performed on separated airway and parenchyma lung tissues to assess transcriptional changes. Validation of a novel upstream driver SPI1 in experimental ACO was assessed using the pharmacological SPI1 inhibitor, DB2313. Results: Experimental ACO recapitulated features of both asthma and COPD, with mixed pulmonary eosinophilic/neutrophilic inflammation, small airway collagen deposition, and increased airway hyperresponsiveness. Transcriptomic analysis identified common and distinct dysregulated gene clusters in airway and parenchyma samples in experimental asthma, COPD, and ACO. Upstream driver analysis revealed increased expression of the transcription factor Spi1. Pharmacological inhibition of SPI1 using DB2313, reduced airway remodeling and airway hyperresponsiveness in experimental ACO. Conclusions: A new experimental model of ACO featuring chronic dual exposures to house dust mite and cigarette smoke mimics key disease features observed in patients with ACO and revealed novel disease mechanisms, including upregulation of SPI1, that are amenable to therapy.
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Nova |
2021 |
Alemao CA, Budden KF, Gomez HM, Rehman SF, Marshall JE, Shukla SD, et al., 'Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders', Allergy: European Journal of Allergy and Clinical Immunology, 76 714-734 (2021) [C1]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmo... [more]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a ¿poor¿ diet or protection against disease with a ¿healthy¿ diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
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Nova |
2021 |
Gomez HM, Pillar AL, Brown AC, Kim RY, Ali MK, Essilfie A-T, et al., 'Investigating the Links between Lower Iron Status in Pregnancy and Respiratory Disease in Offspring Using Murine Models', NUTRIENTS, 13 (2021) [C1]
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Nova |
2017 |
Jones B, Donovan C, Liu G, Gomez HM, Chimankar V, Harrison CL, et al., 'Animal models of COPD: What do they tell us?', Respirology, 22 21-32 (2017) [C1]
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progr... [more]
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.
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Nova |