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Trinity College Dublin

Personal Information
College Photo Name Dunne, Margaret
Main Department Surgery
College Title Research Fellow
E-mail dunnem12@tcd.ie
College Tel  
 
Representations
Details Date
Poster presentation at the 9th International Cancer Conference, Trinity Biomedical Sciences Institute, Dublin Sept 2014
Oral presentation at the 8th National Barrett’s Symposium, University College London April 2014
Presented 2 posters at the Irish Association for Cancer Research annual meeting, Galway Feb 2014
Oral presentations at the Irish Society for Immunology annual meeting 2013, 2009, 2008 & 2007
Poster presentation at the 5th International γδ T cell conference, Freiburg, Germany 2012
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Membership of Professional Institutions, Associations, Societies
Details Date From Date To
Member of the Irish Society for Immunology 2005 Present
Member of the Irish and European Associations for Cancer Research (IACR, EACR) 2013 Present
Member of the γδ T cell forum 2010 Present
 
Awards and Honours
Award Date
Irish Research Council Government of Ireland Postdoctoral Fellow 2014
Dorothy Price medal (NUI Maynooth) 2008
John & Pat Hume Postgraduate Scholarship 2005
Irish Research Council for Science, Engineering & Technology Postgraduate Scholarship 2005
 
Description of Research Interests
My research involves improving the understanding of roles played by innate immune cells in human health and disease, and translation of this information for therapeutic applications. My research projects to date have focussed on elucidating the function of innate lymphocytes, in particular γδ T cells and dendritic cells, in health and disease, and their contribution to host immunity.
 
Research Interests
COELIAC DISEASE COLORECTAL CANCER HUMAN DENDRITIC CELLS HUMAN T-CELLS
Mucosal-associated invariant T cells OESOPHAGEAL ADENOCARCINOMA TCR GAMMA DELTA(+) T CELLS
 
Research Projects
Project title Investigating the role of innate lymphocyte subsets in oesophageal adenocarcinoma - is inflammation a negative regulator of response to therapy?
Summary Oesophageal adenocarcinoma is an aggressive cancer with poor prognosis, and incidence has increased 5-fold in the last 30 years. Multi-modal neoadjuvant therapy, either chemotherapy alone (neo-CT) or combination chemoradiation (neo-CRT) is increasingly adopted as the standard of care, but standard clinicopathological parameters are unable to predict patient responsiveness to these approaches. Approximately 70-80% of patients are unresponsive and may be harmed by the delay to surgery and unnecessary treatment toxicity. Our group is currently leading an international phase III clinical trial, comparing the efficacy of two neoadjuvant regimens for treatment of oesophageal adenocarcinoma – the MAGIC regimen, (3 pre- and 3 post-operative 3 week cycles of chemotherapy), and the CROSS protocol (5 weekly cycles of chemotherapy and 5 weeks of radiation therapy). During this trial, blood and tissue samples will be available (both pre- and post-neo-CRT treatment) and ethical approval has been granted to conduct research studies. We will use these samples to investigate the role of inflammation in oesophageal adenocarcinoma and in response to therapy. It is widely reported that inflammation drives tumour initiation and progression by promoting proliferation and survival of malignant cells, angiogenesis and metastasis, by subverting adaptive immune responses and by altering responses to hormones and chemotherapeutic agents. However, inflammation is also pre-requisite for the generation of an effective anti-tumour adaptive immune response. Clarification of the modes of action of inflammatory mediators will allow exploration of how the prevailing inflammatory response may be directed in favour of adaptive responses rather than tumour development. We aim to evaluate the inflammatory contributions of unconventional innate lymphocytes, specifically γδ T cells (Vδ1, Vδ2 and Vδ3 subsets) and mucosal associated invariant T (MAIT) cells. Despite considerable interest in these cells as immunotherapeutic agents, little information exists on their role in the oesophagus, let alone their potential as therapeutic targets.
Funding Agency Irish Research Council
Programme Postdoctoral Fellowship
Type of Project
Date from
Date to
Person Months


Project title Investigating the role of regulatory T cells in colorectal cancer
Summary
Funding Agency Science Foundation Ireland
Programme
Type of Project Postdoctoral fellowship
Date from Oct 2012
Date to Sept 2013
Person Months 12


Project title Elucidating the role of innate lymphocytes in coeliac disease pathogenesis
Summary Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.
Funding Agency Children's Medical Research Foundation
Programme
Type of Project Postdoctoral fellowship
Date from March 2010
Date to Sept 2012
Person Months 30


 
Publications and Other Research Outputs
Peer Reviewed
Comerford R, Coates C, Byrne G, Lynch S, Dunne P, Dunne M, Kelly J, Feighery C, Characterisation of tissue transglutaminase-reactive T cells from patients with coeliac disease and healthy controls , Clinical Immunology, 154, (2), 2014, p155 - 163
DOI  URL
Dunne, MR, Elliott, L, Hussey, S, Mahmud, N, Kelly, J, Doherty, DG, Feighery, CF, Persistent Changes in Circulating and Intestinal gamma delta T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease, PLOS ONE, 8, (10), 2013, p76008
DOI  URL
Mangan BA, Dunne MR, O'Reilly VP, Dunne PJ, Exley MA, O'Shea D, Scotet E, Hogan AE, Doherty DG, CD1d restriction and Th1/Th2/Th17 cytokine secretion by human Vδ3 T cells, Journal of Immunology, 191, (1), 2013, p30 - 34
O'Shea D, Corrigan M, Dunne MR, Woods C, Gaoatswe G, O’Connell J, Hogan AE, Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection, International Journal of Obesity, 37, (11), 2013
Hogan AE, O'Reilly V, Dunne MR, Dere RT, Zeng SG, O'Brien C, Amu S, Fallon PG, Exley MA, O'Farrelly C, Zhu X, Doherty DG, Activation of human invariant natural killer T cells with a thioglycoside analogue of á-galactosylceramide, Clinical Immunology, 140, (2), 2011, p196-207
TARA - Full Text
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