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Children's Respiratory Group


Brodlie Lab

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Aaron Gardner

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Bio

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).


Research

Cystic fibrosis lung disease

Cystic fibrosis (CF) is the most common genetically-acquired life limiting disorder in the UK, affecting over 10,000 people. 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 multisytem 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 neutrophillic . Current treatments however 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. Significantly raised immunoreactive ceramide in the epithelium of lungs from people with CF compared to emphysema, pulmonary hypertension and unused lung donors have also been found. The level of staining correlated positively with markers of neutrophilic inflammation and P. aeruginosa status.

Ceramide-enriched membrane domains exhibit distinct biophysical properties and are critical in the organisation of inflammatory receptor and signalling molecules.

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
Other interests:
  • The role of dysregulated NF-kB signalling in CFLD
  • Development of novel 3D culture and techniques for primary airway epithelial cells
  • Epithelial/mesenchymal interactions in wound healing and fibrosis

Impact

Willmore E, Gardner A, Tudhope S, Herridge A, Hunter J, Wallis JP, Marr HJ, Berretta G, Breen D, Paul A, Edwards D, Young LC, Suckling CJ, Plevin R, Boyd M, Allan JM, Mackay S & Perkins N. Targeting Ikkα in CLL: Inhibition of Non-Canonical NF-κb Signaling Decreases Survival and Proliferation of CD40L-Stimulated Primary CLL Cells. Blood. 2016; 128(22):3659.

Jahoda CAB, Guo A, Gardner A, Manning C, Roger M, Hill R, Farjo N, Farjo B, Ali-Khan AS, Garlick J, Christiano AM & Higgins CA. Hair follicle-derived dermal stem cells-a novel and improved source of dermis for skin replacement. Br J Dermatol. 2016; 175:49.

Borthwick LA, Suwara MI, Carnell SC, Green NJ, Mahida R, Dixon D, Gillespie CS, Cartwright TN, Horabin J, Walker A, Olin E, Rangar M, Gardner A, Mann J, Corris PA, Mann DA & Fisher AJ. Pseudomonas aeruginosa induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction. American Journal of Transplantation. 2016;16(6):1751-1765.

Haq IJ, Gardner A & Brodlie M. A multifunctional bispecific antibody against Pseudomonas aeruginosa as a potential therapeutic strategy. Ann Transl Med. 2016; 4(1):12.

Willmore E, Gardner A, Tudhope S, Murtani B, Caffry J, Mulligan E, Hunter J, Wallis J, Marr H, Beretta G, Breen B, Paul A, Edwards D, Young L, Suckling C, Plevin R, Boyd M, Mackay S & Perkins N. Novel small molecule IKK alpha inhibitors inhibit non-canonical NF-kappa B signaling and survival of primary CLL cells. Leuk Lymphoma. 2015; 56:108-109.

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Prescott HMA, Manning C, Gardner A, Ritchie WA, Pizzi R, Girling S, Valentine I, Wang C & Jahoda CAB. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells. PLoS ONE. 201510(9):e0138840.

Gardner A, Hill RP, Higgins CA, Whitehouse CJ, Yung S, Zhang X, Crawford HC, Richer R, Dodds A, Owens WA, Lawrence C, Rao S, Kara B, James SE, Lako M & Jahoda CA. Human hair follicle dermal cells provide enhanced support for both epithelial and embryonic stem cell culture proliferation and maintenance. J Invs Dermat. 2013; 133(5):1423.

Brain JG, Robertson H, Thompson E, Humphreys EH, Gardner A, Booth TA, Jones DEJ, Afford SC, von-Zglinicki T, Burt AD & Kirby JA. Biliary epithelial senescence and plasticity in acute cellular rejection. American Journal of Transplantation. 2013;13(7):1688–1702.

Hill RP, Gardner A, Crawford HC, Richer R, Dodds A, Owens WA, Lawrence C, Rao S, Kara B, James SE & Jahoda CA. Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer co-culture. Experimental Dermatology.
2013;22(3):236–238.

Gledhill K, Gardner A & Jahoda CAB. Isolation and establishment of hair follicle dermal papilla cell cultures.
Methods in Molecular Biology – Skin Stem Cells. 2013;989:285–292.

Borthwick LA, Corris PA, Mahida R, Walker A, Gardner A, Suwara M, Johnson GE, Moisey EJ, Brodlie M, Ward C, Perry JD, de Soyza A, Mann DA & Fisher AJ. TNFα From Classically Activated Macrophages Accentuates Epithelial to Mesenchymal Transition in Obliterative Bronchiolitis. American Journal of Transplantation. 2013;13(3):621–633.

Hill RP, Gledhill K, Gardner A, Higgins CA, Crawford H, Lawrence C, Hutchison CJ, Owens WA, Kara B, James SE & Jahoda CA.
Generation and Characterization of Multipotent Stem Cells from Established Dermal Cultures. PLoS ONE. 2012;7(11):e50742.

Gardner A, Fisher AJ, Richter C, Johnson GE, Moisey EJ, Brodlie M, Ward C, Krippner-Heidenreich A, Mann DA & Borthwick LA. The Critical Role of TAK1 in Accentuated Epithelial to Mesenchymal Transition in Obliterative Bronchiolitis after Lung Transplantation. American Journal of Pathology. 2012;180(6):2293–2308.

Borthwick LA, Gardner A, De-Soyza A, Mann DA & Fisher AJ. Transforming Growth Factor-beta1 (TGF-beta1) Driven Epithelial to Mesenchymal Transition (EMT) is Accentuated by Tumour Necrosis Factor alpha (TNFalpha) via Crosstalk Between the SMAD and NF-kappaB Pathways. Cancer Microenvironment. 2012;5(1):45–57.

Borthwick LA, Botha P, Verdon B, Brodlie M, Gardner A, Bourn D, Johnson GE, Gray MA & Fisher AJ. Is CFTR-delF508 Really Absent from the Apical Membrane of the Airway Epithelium? PLoS ONE. 2011;6(8):e23226.

Gardner A, Borthwick L & Fisher A. Lung epithelial wound healing in health and disease. Expert Review of Respiratory Medicine. 2010;4(5):647–660.

Griesenbach U, Meng CX, Farley R, Gardner A, Brake MA, Frankel GM, Gruenert DC, Cheng SH, Scheule RK & Alton EWFW. The role of doxorubicin in non-viral gene transfer in the lung. Biomaterials. 2009;30(10):1971–1977.

  • 14th European Cystic Fibrosis Society Basic Science Conference, 2017. Algarve, Portugal.
    Poster Presentation, Linking cystic fibrosis lung disease pathophysiology with ceramide accumulation and inflammation.
  • 3rd International Conference on the Molecular Medicine of Sphingolipids, 2016. French Lick, USA.
    Oral & Poster Presentation, Investigating the role of pH on ceramide accumulation in cystic fibrosis.
  • UK NF-kappaB Workshop, 2015. Glasgow, UK.
    Poster Presentation, Novel small molecule IKKalpha inhibitors inhibit non-canonical NF-kappaB signalling and survival of primary chronic lymphocytic leukaemia cells.
  • 8th World Congress for Hair Research, 2014. Jeju, South Korea.
    1. Oral & Poster Presentation, Dermal-epidermal interactions in 3D culture restore markers of dermal papilla inductivity.
    2. Oral & Poster Presentation, Follicular dermal cells as potential contributors to enhanced wound resolution.
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  • North East Stem Cell Institute, Annual Research Conference, 2014. Newcastle-upon-Tyne, UK.
    Poster Presentation, Follicular dermal cells as potential contributors to enhanced wound resolution.
  • North East Stem Cell Institute, Annual Research Conference, 2013. Newcastle-upon-Tyne, UK.
    Poster Presentation, Human hair follicle dermal cells provide enhanced support for both epithelial and embryonic stem cell culture proliferation and maintenance.
  • 7th World Congress for Hair Research, 2013. Edinburgh, UK.
    Poster Presentation, Human hair follicle dermal cells provide enhanced support for both epithelial and embryonic stem cell culture proliferation and maintenance.
  • North East Stem Cell Institute, Annual Research Conference, 2012. Newcastle-upon-Tyne, UK.
    Poster Presentation, Passaged human skin dermal fibroblasts: A novel source of multi-potent skin derived precursor cells.
  • Keystone Symposia, Epithelial Plasticity and Epithelial to Mesenchymal Transition, 2011. Vancouver, Canada.
    Poster Presentation, TNFalpha accentuates TGF-beta1 driven Epithelial to Mesenchymal Transition in lung epithelium via TGF-beta activated kinase-1 (TAK-1) dependent signalling.
  • European Respiratory Society, Lung Science Conference, 2011. Estoril, Portugal.
    Poster Presentation, TNFalpha accentuates TGF-beta1 driven Epithelial to Mesenchymal Transition in lung epithelium via TGF-beta activated kinase-1 (TAK-1) dependent signalling.
  • British Association of Lung Research, Summer Meeting, 2011. Newcastle-upon-Tyne, UK.
    Oral Presentation, TNFα accentuates TGF-beta1 driven Epithelial to Mesenchymal Transition in lung epithelium via TGF-beta activated kinase-1 (TAK-1) dependent signalling.
  • British Thoracic Society, Winter Meeting, 2010. London, UK.
    Oral Presentation, The role of Transforming Growth Factor Beta Associated Kinase 1 (TAK-1) in the development of airway fibrosis.
  • European Respiratory Society, Lung Science Conference, 2010. Estoril, Portugal.
    Poster Presentation, TNFalpha accentuates TGF-beta1 driven Epithelial to Mesenchymal Transition (EMT) in lung epithelium via TNFalphaReceptor1 dependent signalling.
  • British Thoracic Society, Winter Meeting, 2009. London, UK.
    Poster Presentation, TNFalpha accentuates TGF-beta1 driven Epithelial to Mesenchymal Transition (EMT) in lung epithelium via TNFalphaReceptor1 dependent signalling.
  • British Society of Gene Therapy, Annual Meeting, 2006. London, UK.
    Poster Presentation, The role of doxorubicin in non-viral gene transfer in the lung.
  • Cystic Fibrosis Trust Summer Studentship 2016, Newcastle, UK.
    Recipient of £1,500 stipend and consumables grant.
  • Wellcome Trust Biomedical Vacation Scholarships 2016, Newcastle, UK.
    Recipient of £2,000 stipend and consumables grant.
  • 8th World Congress for Hair Research 2014, Jeju, South Korea.
    Recipient of €750 travel grant.
  • Keystone Symposia, Epithelial Plasticity and Epithelial to Mesenchymal Transition 2011, Vancouver, Canada.
    Recipient of $1,200 travel grant.
  • British Thoracic Society, Winter Meeting 2010, London, UK.
    Recipient of £500 travel grant.
  • European Respiratory Society, Lung Science Conference 2010, Estoril, Portugal.
    Recipient of €500 travel grant.
  • 8th World Congress for Hair Research 2014, Jeju, South Korea.
    Winner of Best Research Paper oral presentation prize.
  • North East Stem Cell Institute, Annual Research Conference 2014, Newcastle, UK.
    Winner of best poster presentation prize.
  • British Association of Lung Research, Summer Meeting 2011, Newcastle, UK.
    Winner of the Young Investigator oral presentation prize.
  • British Thoracic Society, Winter Meeting 2010, London, UK.
    Nominee for Young Investigator prize.

Supervision & Teaching

2016/2017
  • 1x Newcastle University Biomedical Sciences BSc student
  • 1x Newcastle University MSc Medical Sciences student
2015/2016
  • 1x Newcastle University Biomedical Sciences BSc student
  • 1x Cystic Fibrosis Trust funded summer student
2013/2014
  • Human physiology lectures, seminars and tutorials.
  • 1x Newcastle University Medical and Molecular Biosciences MRes student
  • 2x Durham University Biomedical Sciences BSc students
2012/2013
  • 2x Durham University Biomedical Sciences BSc students

News

Aaron presents his research at the Molecular Medicine of Sphingolipids conference

  24.09.2016   admin   Aaron, CF, Conference, News

Aaron presented his most recent research at the 3rd International Molecular Medicine of Sphingolipids in French Lick, Indiana, USA.

Ali wins poster prize at the CF Trust Conference 2016

  8.09.2016   Aaron   Aaron, CF, Conference, Malcolm, News

Congratulations to Ali! who won the 2nd place prize in the poster competition at the 2016 CF Trust Conference.


Previous Positions & Education

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

Memberships

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