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Dr. Aisling Dunne

Ussher Asst. Prof in Neuroinflammation (Biochemistry)

Ussher Asst. Prof in Neuroinflammation (Physiology)

Details Date From Date To
Member of the Irish Society of Immunology Member of the British Society of Immunology Member of the Irish Area Section of the Biochemical Society
Mahon, O.R. and O'Hanlon, S. and Cunningham, C.C. and McCarthy, G.M. and Hobbs, C. and Nicolosi, V. and Kelly, D.J. and Dunne, A., Orthopaedic implant materials drive M1 macrophage polarization in a spleen tyrosine kinase- and mitogen-activated protein kinase-dependent manner, Acta Biomaterialia, 65, 2018, p426-435 , Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Cunniffe G.M, Díaz-Payno P.J, Ramey J.S, Mahon O.R, Dunne A, Thompson E.M, O†Brien F.J, Kelly D.J, Growth plate extracellular matrix-derived scaffolds for large bone defect healing, European Cells and Materials, 33, 2017, p130 - 142, Journal Article, PUBLISHED  DOI  URL
Corr E.M, Cunningham C.C, Helbert L, McCarthy G.M, Dunne A, Osteoarthritis-associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells, Arthritis Research and Therapy, 19, (1), 2017, p23-, Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
Corr E.M, Cunningham C.C, Dunne A, Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells, Atherosclerosis, 251, 2016, p197 - 205, Notes: [Export Date: 26 September 2016], Journal Article, PUBLISHED  DOI  URL
Basdeo S.A, Campbell N.K, Sullivan L.M, Flood B, Creagh E.M, Mantle T.J, Fletcher J.M, Dunne A, Suppression of human alloreactive T cells by linear tetrapyrroles; relevance for transplantation, Translational Research, 178, 2016, p81-94.e2 , Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
Investigating inflammasome activation under conditions of cellular stress and injury in, Stress Responses: Methods and Protocols, 2015, pp105-113 , [Cunningham C.C, Corr E.M, Cox D.J, Dunne A], Notes: [ ], Book Chapter, PUBLISHED  DOI  URL
Cox, D. J., Field, R. H., Williams, D. G., Baran, M., Bowie, A. G., Cunningham, C. and Dunne, A. , DNA sensors are expressed in astrocytes and microglia in vitro and are upregulated during gliosis in neurodegenerative disease, GLIA, 63, (5), 2015, p812-825 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Dunne A, Mielke LA, Allen AC, Sutton CE, Higgs R, Cunningham CC, Higgins SC, Mills KH, A novel TLR2 agonist from Bordetella pertussis is a potent adjuvant that promotes protective immunity with an acellular pertussis vaccine., Mucosal immunology, 8, (3), 2015, p607-617 , Journal Article, PUBLISHED  DOI
Wochal, P., Rathinam, V.A.K., Dunne, A., (...), Fitzgerald, K.A., O'Neill, L.A.J. , TRIL is involved in cytokine production in the brain following escherichia coli infection, Journal of Immunology, 193, (4), 2014, p1911-1919 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Indranil Basak, Ramavati Pal, Ketan S. Patil, Aisling Dunne, Hsin-Pin Ho, Sungsu Lee, Diluka Peiris, Jodi Maple-Grødem‖, Mark Odell, Emmanuel J. Chang, Jan Petter Larse and Simon G. Møller, Arabidopsis AtPARK13, which confers thermotolerance, targets misfolded proteins, Journal of Biological Chemistry, 289, (21), 2014, p14458-14469 , Journal Article, PUBLISHED  DOI

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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-1â 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 specific signalling events involved in Toll-like receptor signalling as well as the identification of novel TLR and NLR agonists from pathogens such as Bordetella pertussis. We have recently identified novel TLR 2 activating ligands from the bacterium 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 to date has focused on osteoarthritis and atherosclerosis associated basic calcium phosphate crystals. These crystals are known to drive pro-inflammatory cytokine production and they have also recently been identified as putative inflammasome activators. We are currently exploring the signalling events triggered by these crystals in macrophages and synovial fibroblasts in order to identify new targets for the treatment of BCP related arthropathies. Identification of novel endogenous 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 the mechanisms by which the HO system exerts its anti-inflammatory effects on T cells in order to provide further evidence that the heme degradation pathway may be exploited as a potential therapeutic avenue for debilitating autoimmune diseases such as Multiple Sclerosis. Characterisation of a novel brain enriched TLR interacting protein: We have recently identified a novel component of the TLR3 and TLR4 signalling pathway which we have named TRIL (TLR4 Interactor with Leucine Rich Repeats). This protein is highly expressed in the brain and as well as containing the extracellular leucine rich repeats found in TLRs, it also bears structural similarities with members of the NOGO and LINGO receptor family, both of are known to modulate neurite outgrowth. We are currently carrying out a detailed characterisation of this highly novel protein which we believe may represent a new target for neuroinflammatory disease.