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Dr Aisling Dunne

Molecular Immunology


A. Dunne photo

Dr Aisling Dunne
Assistant Professor
Phone: + 353-1-8962437
Fax: + 353 -1-6772400
Email: aidunne@tcd.ie
Location: Room 3.10, Trinity Biomedical Sciences Institute

RESEARCH INTERESTS

The recognition of pathogen-derived molecules by the innate immune system is mediated by a number of receptors, including members of the TLR (Toll-like receptor), RLH [RIG (retinoic acid-inducible gene)-like helicase] and the NLR (NOD-like receptor) families. TLRs bind exogenous pathogen associated molecular patterns (PAMPs), conserved structures expressed by pathogens, such as lipopolysaccharide (LPS), flagellin, viral and bacterial nucleic acids, but also endogenous damage-associated molecular patterns (DAMPs), such as amyloid-beta and fatty acids. NLRs in particular are also involved in the recognition of host-derived DAMPs which are produced under conditions of cellular stress or injury. Activation of these receptors leads to the assembly of high-molecular-mass complexes called inflammasomes which in turn leads to the generation of mature IL-1b and IL-18. The discovery that NLRP3 can recognize host derived particulate matter such as uric acid, cholesterol crystals and IAPP has led to the inflammasome being implicated in a number of inflammatory diseases, including gout, atherosclerosis and Type 2 diabetes. On the other hand, a number of studies have reported that recognition of both viral and bacterial products by NLRs is required for effective pathogen clearance.

Specific areas of interest include:

Identification of novel PAMPs and DAMPs and elucidation of their mechanism of action:
Our research to date has focused on the identification of disease-associated DAMPs and PAMPs. We have been elucidating the specific signalling events triggered by these molecules in primary immune cells. For example, we have recently identified novel TLR 2 activating ligands and potential vaccine candidates from the bacterium Bordetella pertussis (the causative agent of whooping cough) and have elucidated the mechanism by which a pertussis derived toxin activates the NLRP3 inflammasome resulting in the generation of protective TH17 responses. Our work on endogenous DAMPs has focused on disease associated particulates such as basic calcium phosphate crystals which are found at high concentrations in osteoarthritic joints. We are currently exploring the cellular events triggered by these crystals in macrophages, osteoclasts and synovial fibroblasts. We have reported that these DAMPs activate membrane proximal kinases and can drive the activation of bone-resorbing osteoclasts which contributes further to joint destruction. As an extension of our work on osteoarthritis, we have recently begun assessing the immune response to novel biomaterials used for joint replacement surgery in collaboration with The Trinity Centre for Bioengineering.

Identification of novel immunomodulators:
Heme oxygenase (HO)-1 catalyses the rate limiting step in the breakdown of free heme. It has been known for some time that HO-1 inhibits the pathogenesis of several immune-mediated inflammatory diseases. The mechanisms that mediate the anti-inflammatory effects of this enzyme are not fully understood however it has been suggested that the enzymatic degradation of pro-inflammatory free heme and the production of the anti-inflammatory compounds biliverdin/bilirubin and CO may be responsible. We are currently exploring novel HO-1 inducers and the mechanisms by which the HO system exerts its anti-inflammatory effects on peripheral and central immune cells in order to provide further evidence that the heme degradation pathway may be exploited as a potential therapeutic avenue for debilitating autoimmune diseases and inflammatory diseases.

RESEARCH PERSONNEL

Postdoctoral Fellows:
Dr Louise Sullivan
Dr Sharee Basdeo

Graduate students:
Clare Cunningham
Emma Corr
Donal Cox
Glyn Williams
Nicole Campbell

Research Assistant:
NĂ­al Harte

FINANCIAL SUPPORT:

Health Research Board, Science Foundation Ireland, PRTLI 10

COLLABORATORS:

Professor Geraldine McCarthy, Mater Misericordiae University Hospital, Dublin.
Professor Nick Gay, University of Cambridge.
Professor Kate Fitzgerald & Dr Susan Carpenter, University of Massachusetts, Boston.
Professor Luke O'Neill, School of Biochemistry & Immunology, TCD.
Professor Kingston Mills, School of Biochemistry & Immunology, TCD.
Professor Marina Lynch, Trinity College Institute of Neuroscience, TCD.

PUBLICATIONS

Publications


Last updated 7 April 2017 bbutler@tcd.ie (Email).