Our scientific research activities sit at the interface with clinical research to enable translational studies focussed on elucidating molecular mechanisms of asthma and chronic obstructive pulmonary disease (COPD), particularly in relation to the restructuring of the airways that lead to altered pulmonary function. In all of our studies, we place a strong emphasis on the use of disease-derived cells and tissues for use in functional and mechanistic studies in vitro and linking these back to responses in vivo. Thus, an important aspect of our translational research is the close working relationship that exists between clinical and non-clinical scientists who work and train together in the Brooke Laboratory.
The group currently comprises 15 doctoral and post doctoral scientists, including 5 clinical research fellows and benefits by attracting a number of international visitors from Europe and the rest of the world. We also have a number of collaborations within the UK, as well as Europe and the USA. The group is based in the Brooke Laboratories which were refurbished as a result of a generous donation by Mr Roger Brooke and officially opened in March 2001. The complex initially comprised three cell culture laboratories, a molecular biology laboratory, a general laboratory, imaging and radioactivity handling rooms and a suite of offices; these were extended in 2003 by the addition of two new tissue culture laboratories and a protein chemistry lab.
Particular areas of interest include:
- Epithelial responses to viruses, air pollutants (including diesel particles and cigarette smoke) and environmental allergens;
- EGF/c-erbB receptor signalling in epithelial repair and differentiation - especially in relation to mechanisms of mucus hypersecretion;
- Biochemical analysis of IL-4 and IL-13 Receptor function;
- Functional characterization of ADAM33 linked to mesenchymal cell function associated with airway remodelling in asthma and COPD;
- The role of ADAM33 in embryonic lung development;
- Epigenetic regulation of ADAM33;
- Identification of novel disease-related genes and proteins via genomic and proteomic technologies.
This work provides opportunities for interactions with colleagues interested in the genetics of asthma (Dr John Holloway) and in searching for novel molecular pathways in which to intervene more effectively. An example of this is the recent collaboration with Professor Holgate and Dr Howarth showing that treatment with Etanercept (a soluble TNFα receptor fusion protein used to suppress the activity of TNFα in rheumatoid arthritis) is highly effective for treatment of subjects with severe corticosteroid-insensitive asthma [PubMed].
Synairgen In August 2003, Professors Holgate, Davies and Djukanovic co-founded Synairgen, a University of Southampton spin-out company.
Why focus on asthma and COPD>
In the UK, respiratory diseases account for 25 per cent of all medical admissions to hospital, and the majority are due to bronchial asthma or COPD. These diseases are widespread, may be fatal or have severe health consequences. Unlike other disease areas such as cardiovascular where there have been significant new therapeutic treatments such as Statins, which lower cholesterol levels, COPD and asthma have not benefited from any recent major breakthroughs with the exception of Xolair?.
Asthma
Asthma is a disease whose incidence worldwide is increasing in relation to factors linked to a Western lifestyle. It is a condition that has a strong genetic component, so that it tends to run in families. The symptoms of asthma are wheeziness, shortness of breath and cough. Asthma attacks are triggered by innocuous stimuli such as common allergens (house dust, dog or cat fur), viruses, air pollutants, cold air or exercise, making it difficult for asthmatic people to do normal every day activities. The problem is due to asthmatic airways being 'twitchy' or hyper-responsive so that, during an asthma attack, the airways narrow too much and too easily making it difficult to breathe; in severe attacks, this can be fatal. This 'twitchiness' is due to a special kind of inflammation and changes in the structure of asthmatic airways, which are thicker than normal due to chronic swelling, fibrotic changes and enlargement of the bronchial muscles.
Histopathology
Histopathology of an asthmatic airway showing marked inflammation throughout the bronchial wall and a large increase in smooth muscle.
Asthma is estimated to affect approximately 10 per cent of the population in the industrialised world and the number of asthmatics is increasing. In the UK, asthma affects 1 in 5 children and 1 in 10 adults and the total cost of care ranges from £835 p.a. for mild asthmatics to £3996 p.a. in severe chronic cases. Asthma prevalence is now three to four times higher in adults and six times higher in children than it was 25 years ago and currently accounts for 1 in 250 of all deaths. In the US there are approximately 15 to 17 million sufferers with the financial cost of the disease estimated to be about $15 billion per annum. In the UK, approximately 74,000 people are admitted to hospital and almost 1,500 die from asthma every year. Asthma accounts for 12 per cent of total annual UK NHS prescriptions.
Link to Asthma UK: All about asthma
COPD
COPD encompasses a number of diseases including the smoking-related lung diseases, Emphysema and Chronic Bronchitis. These conditions are characterised by various pathologies including degeneration and destruction of the lung and supporting tissues, over production of mucus (leading to an increased risk of infection) and fibrosis of the small airways. COPD is the cause of death in 6 per cent of men and 4 per cent of women, amounting to 30,000 deaths per annum in the UK alone. It is believed to be the fourth largest cause of death in the US and is estimated to become the third largest cause of death worldwide by 2020. Smoking is the most common reason for developing COPD, estimated to be responsible for 80 to 90 per cent of all cases. Interestingly, only around 15-20% of long term smokers develop clinical symptoms of COPD, suggesting that there is an underlying genetic susceptibility that influences the development of the disease. The total cost of COPD to the US was estimated at $32.8 billion in 2001 and is expected to exceed $55 billion in 2008. There are no therapeutic treatments currently available which have been developed to effectively treat COPD.