Aaron is currently employed as a post-doctoral research associate within the Children's Respiratory Group at Newcastle University.
His major research interests include the role of sphingolipids in the development of cystic fibrosis lung disease and associated therapeutic targets, the development of novel culture techniques for pulmonary research and wound healing, and the use of machine learning to model disease progression.
I am currently employed as a post-doctoral research associate in Dr Malcolm Brodlie’s lab which forms the Children’s Respiratory Group within the wider Respiratory Research Group. My project is focused on understanding the role of alterations in sphingolipid metabolism on the development of cystic fibrosis lung disease (CFLD). The underlying cause of CF is loss of, or reduced function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes for an apical chloride and bicarbonate transporter expressed by epithelial cells. However, the exact mechanisms linking defective CFTR function with the pathology of CFLD remain poorly understood.
Sphingolipids are highly biologically active and there is growing evidence that sphingolipid metabolism is implicated in the pathogenesis of several inflammatory lung diseases including emphysema, asthma, acute lung injury and CF. Levels of the sphingolipid ceramide have been found to be raised in the airway epithelium of CF mice and accumulation is linked to neutrophilic inflammation and susceptibility to Pseudomonas aeruginosa infection. The main aim of my project has been to use gold standard techniques (differentiated primary human CF and non-CF airway ALI culture, mass-spectrometry) to accurately assay various sphingolipids, including ceramide, at baseline and in the presence of a novel potential therapeutic agent. A major aspect of the research has been the generation, manipulation and analysis of large data sets requiring the use of bioinformatic and other computational techniques.
Pilot data generated during this project led to a successful funding application (Puffin Appeal - see below). The project is attempting to understand the molecular mechanisms which drive the pro-colonization effects of ceramide and anti-microbial character of sphingosine, and how these effects may be mediated in CF.
Alongside this main project I have also independently driven several side studies including: investigating the role of the cRel NF-κB subunit in the development of inflammation in CF; developing novel 3D culture techniques for human nasal and bronchial airway cells (allowing for more rapid differentiation and high throughput screening); and epidemiological studies into the prevalence of non-tuberculous mycobacteria in the CF population, using a registry-based analysis.