Respiratory Disease Research
Thanks to a number of donors who wished to alleviate the burden of respiratory disease, the MRF were able to support five emerging UK research leaders to drive forward understanding and ultimately improve the lives of patients living with rare lung diseases.
Mesothelioma is a rare and devastating cancer that develops in the cavity that lines the lungs and is largely triggered by the inhalation of asbestos. The average survival time from diagnosis is 9-12 months, with a 5-year survival rate of only 2%. The UK has one of the highest death rates in the world from mesothelioma and sadly there are limited effective therapies available to those who develop it.
Dr Donna Small, Queens University Belfast
Title: Does secretory leukocyte proteinase inhibitor (SLPI) promote Th17 inflammation and poor host immune surveillance in malignant pleural mesothelioma (MPM)?
High levels of a protein inhibitor have been reported in the lung cavity of mesothelioma patients and leads to more inflammation due to the increased levels of a secreted protein (Interleukin-17) released from white blood cells. Dr Donna Small from Queen’s University Belfast was awarded a fellowship to understand the relationship between the protein inhibitor and interleukin-17 and the effect this relationship has on the inflammatory response and subsequent tumour growth in patients with mesothelioma. We hope that the research will provide the knowledge base for developing treatments for mesothelioma that create a less inflammatory environment in the lung and that this approach could result in smaller, less aggressive tumours that respond better to therapy.
Cystic Fibrosis research
Cystic Fibrosis (CF) is another rare lung disease with a poor prognosis. Its incidence varies across the globe and in the European Union; 1 in 2,000-3,000 new-borns are affected. CF is a genetic disorder caused by mutations in a gene that leads to the build-up of abnormally thick mucus in the bodies’ passageways, in particular in the lining of the lungs. The mucus provides a favourable environment for bacteria to grow and increases the susceptibility of CF patients to fatal lung infections.
Dr Jo Fothergill, University of Liverpool
Title: Exploiting novel technologies to identify respiratory pathogens and characterise bacterial interactions in patients with cystic fibrosis.
Lung infections in patients with CF have been shown to have lots of different bugs that can survive despite antibiotics. We don’t know, however, how the different bugs interact with one another, how they survive antibiotics and what impact this has on patients.
If infection is detected early, aggressive antimicrobial treatment can clear it, but any later, treatments are only able to keep infection at bay. It is thought that bacteria may initially live in the nose and sinuses before they move into the lungs and cause infection. Dr Jo Fothergill from the University of Liverpool was awarded a fellowship to determine if new technology can be used to identify bacteria in the nasal passageway by analysing respiratory samples from the lungs of patients with CF. She will also look at how these infecting bacteria interact and look for genes that might make them resistant to antibiotics – a devastating complication for CF patients. We hope that developing new diagnostic approaches for the earlier detection of infection and the rapid identification of antibiotic resistant bacteria could lead to better, earlier and more targeted treatments which will improve long-term outcomes for people living with CF.
Dr James Garnett, University of Newcastle
Title: Role of glucose in Cystic Fibrosis lung: friend or foe in respiratory infections?
It is known that people with Cystic Fibrosis have higher levels of glucose in their lungs than those unaffected and CF-related diabetes develops in 50% of adults with CF. Glucose is a vital energy source for humans and bacteria alike. Glucose is important for the bacteria that cause lung infections and for the white blood cells (phagocytes) that try to kill them. Glucose is a critical energy source for bacteria and is associated with an increased risk of infection in CF patients. In contrast, glucose is also an important energy source for white blood cells which protect the body from infection. Dr James Garnett from Newcastle University was awarded a fellowship to understand how glucose levels are controlled in the airways to provide the correct balance – enough to allow the white blood cells to fight infection, but not so much that it creates a favourable environment for bacterial survival and growth. This research is crucial in determining the role glucose plays during lung infections in people with CF and modulating glucose levels may prove to be a novel therapeutic approach to CF.
Idopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is an incurable rare lung disease and 15,000 people in the UK are living with IPF. The key feature of IPF is the irreversible build-up of dense scar tissue within the air spaces of the lungs, which leads to breathlessness and ultimately respiratory failure. The causes are unknown, and current treatments do not stop the progression of disease, only slow it down.
Dr Franco Conforti, University of Southampton
Title: Investigation of the epithelial-mesenchymal trophic unit in idiopathic pulmonary fibrosis.
To help address this we awarded Dr Franco Conforti from the University of Southampton a fellowship to fill the gap in the understanding of the factors that drive the disease. Alveolar cells in lungs are important for the breathing process and are injured in IPF. Other cells in lungs, fibroblasts, which are usually responsible for promoting wound healing become abnormal in IPF and produce excess scar tissue. Fibroblasts are likely to produce mediators that damage the alveolar cells further, but little is known about how these cells interact to cause abnormal wound-healing and exaggerated scarring. Dr Conforti’s research will look at the interaction and try to determine if alveolar cells can be protected from the damaging effects of the fibroblasts.
Dr Amanda Tatler, University of Nottingham
Title: Elk1 as a master regulator of fibrogenesis: An investigation of the molecular mechanisms through which Elk1 may regulate lung fibrosis
We awarded Dr Amanda Tatler from the University of Nottingham a fellowship to look at how low levels of a protein called Elk1 leads to the development of significantly worse scarring of the lung in patients with IPF. Elk1 is expressed by all cells in the body and is responsible for switching certain genes on or off when required by a cell. Elk1 might act as a “brake” on the scarring process that characterises IPF and block the progression and development of IPF. It is known that patients with IPF have lower levels of the “brake” Elk1 than patients not suffering from IPF. Dr Tatler’s study will use state-of-art molecular techniques to identify different biological pathways that may be important in IPF and are affected by the loss of Elk1 observed in IPF patients. The study aims to analyse the role that Elk1 may play as a master regulator of scarring in human IPF patients and shed important light on how IPF is initiated and progresses.