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Aaron Ions Gardner

Post-doctoral research associate

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.


Profile

Address:
Translational and Clinical Research Institute,
2nd Floor William Leech Building,
Newcastle University,
The Medical School,
NE2 4HH, UK
Aaron Ions Gardner

Background & current research

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 in CF

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.

Other ongoing research

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.

General 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
  • The use of genetic data in personalised medicine
  • Improving educational metrics through the use of novel learning technologies

Teaching & Supervision

Teaching

2017 –

Newcastle University, Undergraduate Biomedical Sciences

2x lectures and 3x seminars; Respiratory and renal physiology
2x lectures; Health and disease at mucosal surfaces.

2013 – 2014

Durham University, Undergraduate Biomedical Sciences

2x lectures and 3x seminars on applied physiology.

Supervision

  • One PhD student (Newcastle University, 2019 – 2021)
  • One MD student (Newcastle University, 2019 – 2021)
  • Three MRes students and one MSc student (Newcastle & Durham University, since 2013)
  • Two Cystic Fibrosis Trust, and one Wellcome Trust funded, summer students (Newcastle University, 2016 & 2017)
  • Eight undergraduate students (Newcastle & Durham University, since 2012)

  • Selected Publications

    2019
    Gardner AI, McClenaghan E, Saint G, McNamara PS, Brodlie M, & Thomas MF. Epidemiology of nontuberculous mycobacteria infection in children and young people with cystic fibrosis: analysis of UK Cystic Fibrosis Registry. Clin Infect Dis, 68(5):731-737.
    doi:10.1093/cid/ciy531

    2019
    Gardner AI, Stauffer S, Petley-Ragan L, Wismer P & Ungu DAK. Labster Virtual Lab Experiments: Genetics of Human Disease.
    doi:10.1007/978-3-662-58744-7

    2018
    Becker KA, Riethmuller J, Seitz AP, Gardner A, Boudreau R, Kamler M, ... Gulbins E. Sphingolipids as targets for inhalation treatment of cystic fibrosis. Adv Drug Deliv Rev.
    doi:10.1016/j.addr.2018.04.015

    2017
    Grassme H, Henry B, Ziobro R, Becker KA, Riethmuller J, Gardner A, ... Gulbins E. beta1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections. Cell Host Microbe, 21(6), 707-718 e708.
    doi:10.1016/j.chom.2017.05.001


    Funding

    2019
    Wellcome Trust; Institutional Strategic Support Fund - Deep learning in healthcare, cystic fibrosis. (£1,251)

    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)

    2017
    Medical Research Council; Confidence in Concept - Reducing ceramide levels in the airway epithelium as a novel therapeutic strategy in cystic fibrosis.(£13,402)
    Wellcome Trust; Institutional Strategic Support Fund - In vivo effects of normalising ceramide in cystic fibrosis. (£1,856)
    Cystic Fibrosis Trust; Summer Studentship. (£1,500)

    2016
    Cystic Fibrosis Trust; Summer Studentship. (£1,500)
    Wellcome Trust Summer; Studentship. (£2,000)

    2014
    European Hair Research Society Travel Grant. (£1,000)

    2010
    British Th oracic Society Travel Grant. (£600)
    European Research Society Travel Grant. (£500)

    Awards

    2017
    Best oral presentation; Institute of Cellular Medicine Directors' Day, Newcastle, UK.

    2014
    Best Research Paper oral presentation prize, 8th World Congress for Hair Research, Jeju, South Korea.
    Best Poster Presentation, North East Stem Cell Institute Annual Research Conference, Newcastle, UK.

    2011
    Best Young Investigator oral presentation prize, British Association for Lung Research Summer Meeting, Newcastle, UK.

    Other Positions, Associations & Memberships

    2015 –

    Global Language Coordinator, Labster ApS, Copenhagen, Denmark

    An ongoing position within the EduTech startup Labster, who specialize in delivery virtual reality laboratory experiences. Developing from a freelancer position I now provide language and scientific support throughout the development of all new scientific simulations.

    Previous Positions

    2015

    Post-doctoral Research Associate: Northern Institute for Cancer Research, Newcastle University, UK

    A six month post-doc position where I investigated the role of IKKα inhibitors as a therapy in chronic lymphocytic leukemia.

    2014

    Visiting Research Associate: Columbia University, New York, USA

    For three months I worked as a visiting research associate in the Department of Dermatology at Columbia University. My project was an independently funded (for which I was a co-applicant) spin-out of my previous position and involved the introduction of genetically modified organoids into neonatal human donor skin in an attempt to maximize hair follicle development and identify molecular signatures that may be relevant in an adult system.

    2011 – 2014

    Post-doctoral Research Associate: School of Biological and Biomedical Sciences, Durham University, UK

    My project was based on investigating hair follicle induction from primary human hair follicle cells. These cells lose their follicle-inducing character in culture, nullifying attempts to expand this population ex vivo. Using genetic (transfection) and environmental (co-culture, 3D culture, organoid formation and air-liquid interface (ALI) culture) re-programming techniques we attempted to improve the inductivity of these cultures, whilst simultaneously dissecting the molecular pathways involved, prior to in vivo proof of principle surgeries, grafting adult human skin onto receptive mouse models.

    2005 – 2006

    Research Assistant: National Heart & Lung Institute

    As part of my studies I undertook a year in industry with the Gene Therapy group at the National Heart and Lung Institute, focusing on improving the efficacy of CF gene transfer to the lung via novel delivery methods and performing chemical inhibition of proteasome function in primary human airway cultures and in vivo models of CF.

    Education

    2008 – 2011

    PhD: Institute of Cellular Medicine, Newcastle University, UK

    PhD focused on understanding the signalling mechanisms involved in the development of fibrotic lung disorders such as bronchiolitis obliterans syndrome. Specifically, I investigated the synergy between fibrotic and inflammatory factors in driving the process of epithelial to mesenchymal transition in primary human bronchial epithelial cells, through molecular interrogation of key signalling pathways.

    2007 – 2008

    MRes: Newcastle University, UK

    MRes in medical and molecular biosciences. My research project investigated the feasibility of using cord-blood stem cells as a source of pluripotent stem cells for tissue engineering.

    2003 – 2007

    BSc: University of York, UK

    BSc in genetics with a year in industry, with a major focus on basic genetics and the genetics of human disease. My final year research project attempted to model the spread of genes through various populations using C++.