'FROM DISCOVERY TO RECOVERY'
My principal research interests are as follows:
1. Clinical assessment and mechanisms of difficult asthma including identification and management of poor adherence.
Difficult asthma represents 5 - 10% of adult asthmatics but this group utilises ca 60% of NHS asthma spend, with repeated unscheduled healthcare contact. Our initial programme of research developed and validated a multi-disciplinary systematic assessment / management model for difficult asthmatics, and defined best practice in this area.
I founded and now co-ordinate the BTS UK Severe Asthma Network and National Registry on Difficult Asthma (see above). The Registry, as well as standardising UK specialist clinical services, facilitates research into the assessment and clinical management of difficult asthma.
My non-adherence research programme has defined, for the first time, the significant scale of this problem in difficult asthma (30 - 50% of subjects) and my Research Nurse, Dr Gamble PhD was awarded Royal College of Nursing Research Nurse of the Year 2010, received a Special Research Award from Asthma UK and was awarded the JD Williamson prize 2010 for best doctoral research in QUB.
My group's current research is developing methods to better identify and manage this problem in the clinic and we have recently developed a novel clinical test using exhaled nitric oxide suppression, and for this work, my Clinical Fellow, Dr McNicholl, won an American Thoracic Society 2010 Travel Award, the UK Respiration Forum Young Investigator Award 2009, and the 2010 Research Medal, NICHS 6th Research Conference.
In collaboration with Genentech, we are developing clinical biomarkers for steroid resistance and exposure and validating the latter as a clinical test for non-adherence. We are developing important collaborations with Professors Rob Horne (University of London) & Professor Paul Cullinan (Imperial) in this area.
We are also examining the role of managing co-morbidity e.g. depressive illness, hyperventilation in this difficult asthma patient group.
2. Epithelial / environmental interactions and onset of wheezing in childhood.
I have pioneered non-bronchoscopic sampling of paediatric airways and have established important in vitro cell models, including a differentiated paediatric epithelial cell model. My group has identified important fundamental differences in the paediatric asthmatic epithelium and our current focus is to examine the mechanism of these abnormalities at transcriptional and translational level. This work has won a number of Research prizes, including the Young Investigator Prize at the British Thoracic Society Winter Meeting 2009.
We have also developed a differentiated nasal epithelial model and have demonstrated using this differentiated system that the nasal response is different and not representative of the bronchial system (manuscript in preparation). With colleagues, I am currently examining opportunities to expand this model to a co-culture system with bronchial smooth cells and differentiated neuronal cells.
In addition, using our paediatric epithelial cell culture model, we have developed a programme with a long-term goal of developing a Respiratory Syncytial Virus vaccine (with Dr U Power, QUB), and we are currently in a programme defining a genetic signature of severe RSV disease.
3. Mechanistic studies in refractory asthma.
The hallmark of refractory asthma is relative steroid resistance and the precise mechanism of this remains unclear; we have recently demonstrated that 2 favoured mechanisms, specifically downregulation of HDAC2 / upregulation of GR-b (dominant negative isoform of glucocorticoid receptor) expression are not as relevant in refractory asthma as previously thought (manuscript under review). My current research strategy, in separate collaborations with Industrial partners [Genentech Inc and Medimmune] is to utilise whole genome expression profiling in bronchial biopsies and epithelial cell brushings to examine other steroid resistance pathways in this refractory group.
Any Translational Medical strategy must utilise early ‘proof of concept' studies and subsequent larger multi-Centre clinical trials. I have substantial experience of interaction with the Pharmaceutical Industry in Phase II / III clinical trials in including study concept and design, establishment of methodology, final protocol review and data analysis.