The Respiratory and Allergy Group operates at the clinical interface to dissect mechanisms of respiratory diseases, define biomarkers of disease severity and translate these findings into novel therapies.
Research Focus
The Respiratory and Allergy Group operates at the clinical interface to dissect mechanisms of respiratory diseases, define biomarkers of disease severity and translate these findings into novel therapies.
Bronchi are the tubes that conduct air to air sacs (alveoli) where gas exchange occurs in the lungs. We are investigating a range of chronic inflammatory airways diseases, including asthma, rhinitis, chronic obstructive pulmonary disease (COPD), primary ciliary dyskinesia (PCD) and cystic fibrosis, using relevant lung-derived samples, which can be used outside the body (ex-vivo) as models of disease in which the underlying mechanisms and novel drugs can be studied.
Airways diseases are characterized by the presence of persistent inflammation, which may be driven by a variety of mechanisms (e.g. allergens, environmental pollutants or persistent infections) depending on the disease. They are usually also associated with alterations in tissue architecture, terms remodeling, leading to impaired lung function and a reduced quality of life. A major unmet need in these diseases is prevention of exacerbations (worsening of symptoms), which can often result in hospital admission or even death.
A particular strength of the Respiratory and Allergy Group is the close links between pediatric and adult research in the lung, providing a distinctive life-course perspective of disease development and progression. Our work is recognised internationally for its translational approach ranging from epidemiology and genetics, cell and molecular biology, biochemistry, pathology, therapeutic target discovery, biomarker discovery and validation, lung imaging, early proof of pharmacological efficacy, to phase I-III clinical trials. The seamless interface between basic and clinical research is facilitated by our NIHR-funded - Respiratory Biomedical Research Unit.
Key Achievements
Important recent achievements of the Respiratory and Allergy Group include the following:
Experimental use of anti TNFα therapy.
Proof of concept trial of Keratinocyte Growth Factor following the discovery that epithelial barrier function is impaired in asthma.
Identification of novel therapeutic targets including CCR4, which was shown to play a key role in T cell recruitment in asthma.
The group has shown that maternal allergy and IL-13 can lead to airway remodelling in early life via ADAM33, which it previously discovered to be an asthma susceptibility gene.
Developing a new focus on epigenetic mechanisms in asthma with a view to investigating transgenerational mechanisms of pathogenesis, it has shown, for example that MicroRNA-155 targets IL13 pathways in macrophages and that the hypersensitivity site V has an important role in shaping chromatin structure in differentiating CD4+T cells
Monitoring the natural history of asthma and allergies through the Isle of Wight Birth Cohort and the Allergy Prevention Study has led to the identification of other susceptibility genes for asthma in children, including ATPAF1.
Collaborations and Enterprise
The Group leads in the identification and validation of biomarkers of airways disease, having co-founded UBIOPRED (http://www.imi.europa.eu/content/u-biopred), a €22m programme in severe asthma funded by the EU and several pharmaceutical companies
It also plays a leading role in the NIHR Translational Research Partnership and the MRC/ ABPI COPD initiative, “COPDMAP” (http://copdmap.com/).
In adult asthma, the Group was the first to show that airway remodelling is a consequence of bronchoconstriction and not ongoing inflammation, which has implications for asthma management.
The Respiratory group provided an important cornerstone for our strategic investment in infectious disease and in Chronic Obstructive Pulmonary Disease (COPD); it has made major contributions to understanding infection-induced exacerbations which has attracted a strategic collaboration with GlaxoSmithKline (GSK) to help develop new vaccines for COPD.
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