Professor Sampson's research over 38 years explored the roles of eicosanoids and related lipid mediators in inflammatory diseases to support the development of novel therapies and optimise the use of existing drugs. A number of studies characterised the cellular expression of enzymes of the leukotriene (5-lipoxygenase) and prostanoid (cyclooxygenase) pathways in human tissues in health and disease. These studies include immunohistochemical analyses of biopsies from patients with allergic asthma, aspirin-intolerant asthma, viral-induced wheezing, allergic rhinitis, urticaria and eczema. Distinct patterns of enzyme expression were related to disease severity and to responsiveness to triggers including allergens and aspirin. Measurements of lipids in bronchoalveolar lavage fluid, blood, urine and sputum have supplemented this approach, and a grant from the AAIR Charity helped to develop quantitative PCR assays for key enzymes and receptors. Professor Sampson's group was the first to identify abnormal expression of leukotriene C4 synthase (LTC4S) in the upper and lower airways as a key immunopathological characteristic underlying of Aspirin-Excerbated Respiratory Disease (AERD), a severe asthma syndrome associated with high mortality and acute sensitivity to NSAID ingestion.
Barrett’s oesophagus is a premalignant condition associated with acid reflux which carries a high risk of progression to oesophageal adenocarcinoma. Previous studies have suggested an involvement of prostanoids in this progression, but in studies with Dr Praful Patel (Gastroenterology, SGH) and DM students funded by the Wessex Cancer Trust (Drs J Shutt, P Boger, J Neale) we showed relationships between 5-LO expression, leukotriene synthesis and disease status along the Barrett’s – adenocarcinoma spectrum. Laser microdissection is being applied to further localise these inflammatory changes.
The group has a long history of interest in studying the immunological and genetic factors that regulate lipid mediator production and release in inflammatory cells isolated from the lungs and circulation of healthy donors and patients with airway disease. The capacity of cytokines to regulate the 5-LO pathway was studied in blood eosinophils and neutrophils and in lung epithelial cells and fibroblasts. We also explored the role of BLT2 receptors in T-lymphocyte proliferation and apoptosis (with Dr C Pickard and Prof E Healy). The isolation of cells from resected human lung tissue (with Dr Jane Warner) enabled new approaches relevant to lung disease, including a macrophage model of AERD and co-supervision of a new BBSRC/CASE studentship with GSK to examine angiotensin receptor pharmacology on human lung fibroblasts.
The demographic of populations worldwide is changing. People are living longer but with more years with affected by disability in the last two decades of life. The societal and economic consequences of this change are not being well managed. There is a lag in the development of health interventions and a need for rapid learning for future health and infrastructure planning. Typically, people in poorer economic situations are disproportionately affected by disability in later life.
Hearing loss and dementia: I lead multidisciplinary research focussed on hearing loss, the use of cochlear implants to restore hearing in otherwise deaf people and the interaction between hearing loss and dementia.
My focus is understanding cellular mechanisms in these conditions and also how the learning and methodologies used to investigate this can be applied across discipline boundaries. I am driving the implementation of data science methodologies for improved management of people who hear with cochlear implants and for the identification of early indicators of cognitive decline. I am championing the engagement of patients in research and as ambassadors to increase awareness of healthcare interventions amongst hard to reach and marginalised communities.
