Institute of Cellular Medicine

Staff Profile

Dr Aaron Gardner

Research Associate

Background

I am currently employed as a post-doctoral research associate in the Children's Respiratory Group within the wider Respiratory Research Group.

Research Interests

  • Effects of dysfunctional CFTR on sphingolipid metabolism in epithelial cells
  • Mechanistic links between ceramide accumulation in epithelial cells and inflammation
  • Therapeutic strategies to modulate sphingolipid metabolism in CF lung disease
  • The role of dysregulated NF-kB signalling in cystic fibrosis lung disease
  • Development of novel 3D culture and techniques for primary airway epithelial cells
  • Epithelial/mesenchymal interactions in wound healing and fibrosis
  • Antimicrobial characteristics of key sphingolipids in cystic fibrosis
  • Neural networks for disease prediction

Funding

2018/2019
  • Wellcome Trust; Institutional Strategic Support Fund - Deep learning in healthcare, cystic fibrosis (£1,251)
2017/2018
  • Newcastle upon Tyne Hospitals NHS Charity ( JRESC); Puffin Appeal - Investigating the antimicrobial activity of sphingosine as a novel therapy against respiratory infection in children (Co-applicant, £181,792)
2016/2017
  • Medical Research Council; Confidence in Concept - Reducing ceramide levels in the airway epithelium as a novel therapeutic strategy in cystic fibrosis (Co-applicant, £13,402)
  • Wellcome Trust; Institutional Strategic Support Fund - In vivo effects of normalising ceramide in cystic fibrosis (£1,500)
  • Cystic Fibrosis Trust; Summer Studentship (£1,500)
2015/2016
  • Cystic Fibrosis Trust; Summer Studentship (£1,500)
  • Wellcome Trust Summer; Studentship (£2,000)

Previous Positions

  • Post-doctoral Research Associate - Northern Institute for Cancer Research, Newcastle University, UK. 2015
  • Post-doctoral Research Associate - School of Biological and Biomedical Sciences, Durham University, UK. 2011-2014
  • Research Assistant - National Heart and Lung Institute, Imperial College, UK. 2005-2006

Education

  • PhD, Cell Signalling in Idiopathic Pulmonary Fibrosis - Newcastle University, UK. 2008-2011
  • MRes, Medical and Molecular Biosciences - Newcastle University, UK. 2007-2008.
  • BSc, Genetics - The University of York, UK. 2003-2007

Honours and Awards

  • Best Research Paper oral presentation prize, 8th World Congress for Hair Research, Jeju, South Korea. 2014
  • European Hair Research Society Travel Grant, 2014
  • Best Poster Presentation, North East Stem Cell Institute Annual Research Conference, Newcastle, UK. 2014
  • Best Young Investigator oral presentation prize, British Association for Lung Research Summer Meeting, Newcastle, UK. 2011
  • Keystone Symposia Travel Grant, 2011
  • British Thoracic Society Travel Grant, 2010
  • European Research Society Travel Grant, 2010

Memberships

  • European Cystic Fibrosis Society, Member
  • British Association for Lung Research, Member
  • European Respiratory Society, Member

External Interests


Research

I am currently employed as a post-doctoral research associate in the Children's Respiratory Group within the wider Respiratory Research Group. My project is focused on understanding the role of alterations in sphingolipid metalobilsm on the development of cystic fibrosis lung disease (CFLD).

Background

Cystic fibrosis lung disease
Cystic fibrosis (CF) is the most common genetically-acquired life-limiting disorder in the UK, affecting over 10,000 people (~80,000 people globally). The underlying cause of CF is mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes for an apical chloride and bicarbonate transporter expressed by epithelial cells. CF is a multisystem condition, but it is lung disease that is responsible for the vast majority of morbidity and mortality. CFLD is characterised by chronic endobronchial inflammation, infection and retention of airway secretions. However, the exact mechanisms linking defective CFTR function with the pathology of CFLD remain poorly understood.
The role of disordered sphingolipid metabolism

Neutrophilic airway inflammation is a key feature in CF and has been detected in young infants. There is also evidence that CF airway epithelial cells also generate exaggerated inflammatory responses independently of neutrophilic recruitment. However, many current treatments only target infection and secretion clearance rather than inflammation - the actual process that mediates lung damage.


Sphingolipids are highly biologically active and there is growing evidence that sphingolipid metabolism is implicated in the pathogenesis of 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 - key features of lung disease in people with CF. 

We have demonstrated that ceramide is elevated in the airway of people with CF, and that this elevation correlates with increased secretion of inflammatory mediators, and also susceptibility to infection. A thorough investigation of sphingolipid metabolism has identified that dysregulation of several key enzymes, as well as altered gene and protein expression likely, plays a key role in this effect.

Furthermore, this dysregulation may lead to an altered cellular response to certain stimuli, such as Pseudomonas aeruginosa infection, which may lead to the development of chronic infection over time.

We are currently investigating mechanisms to target ceramide accumulation therapeutically whilst also investigating basic molecular interactions that may further promote its accumulation, and other physiological processes that are relevant to CF.

Current work:
  • Effects of dysfunctional CFTR on sphingolipid metabolism in epithelial cells
  • Mechanistic links between ceramide accumulation in epithelial cells and inflammation
  • Therapeutic strategies to modulate sphingolipid metabolism in CF lung disease
  • Antimicrobial characteristics of key sphingolipids in cystic fibrosis
Other interests:
  • The role of dysregulated NF-kB signalling in CFLD
  • Development of novel 3D culture and organoid techniques for primary airway epithelial cells
  • Epithelial/mesenchymal interactions in wound healing and fibrosis
  • Neural networks as diagnostic tools
Links:

Teaching

Teaching

2018/2019
  • Undergraduate Physiology lecturing (3x lectures) - Respiratory and renal physiology. (Very high national rating)
  • Undergraduate Biomedical Science lecturing (2x lectures) - Health and disease at mucosal surfaces.
2017/2018
  • Undergraduate Biomedical Science lecturing (2x lectures) - Health and disease at mucosal surfaces.
2013/2014
  • Undergraduate Biological Sciences lecturing (Durham University, 2x lectures & 3x seminars) - Applied physiology.

Supervision

2018/2019
  • Co-supervising MD student as part of "Investigating the antimicrobial activity of sphingosine as a novel therapy against respiratory infection in children" project.
  • 1x Newcastle University Biomedical Sciences BSc student
2017/2018
  • 2x Newcastle University Biomedical Sciences BSc student
  • 1x Newcastle University Biomedical MRes student
2016/2017
  • 1x Newcastle University Medical Sciences MSc student
  • 1x Newcastle University Biomedical Sciences BSc student
  • 1x Cystic Fibrosis Trust funded summer student
2015/2016
  • 1x Newcastle University Biomedical Sciences BSc student
  • 1x Cystic Fibrosis Trust funded summer student
2013/2014
  • 1x Newcastle University Medical and Molecular Biosciences MRes student
  • 2x Durham University Biomedical Sciences BSc students

Publications