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Dr. Michael Gallagher

Senior Research Fellow (Histopathology)
COOMBE WOMENS HOSPITAL


After gaining a PhD (Molecular Genetics) from University College Dublin, Michael Gallagher travelled to Singapore to pursue a career in stem cell biology as a Post-Doctoral Research Fellow at the Genome Institute of Singapore. Michael returned to Ireland in 2005 to establish, develop, and lead Ireland's only pure Cancer Stemness Research Group. In TCD, Michael has established a substantial, high-level research group, which has attracted more than 10 million euros of National and International funding directly and collaboratively, and produced a collection of quality publications including book chapters, reviews and research articles. The majority of cancer deaths are due to development of treatment-resistance disease. It is known that treatment-resistance is associated with tumour-initiating Cancer Stem Cells (CSCs). However, CSC-targeting has not been efficiently translated to the clinic. This is likely due to the complex organisation of CSCs as Stem-Progenitor-Differentiated cell Hierarchies within the tumour. Addressing this, Michael developed a single-cell analysis, CSC Discovery Pipeline, which facilitates the identification and characterization of CSC hierarchies. To date, our research has identified novel CSCs in lung, prostate, and oesphageal cancers, as well as a CSC Hierarchy in ovarian cancer. In 2017, Michael became the first researcher to demonstrate the treatment-resistance is the property of specific types of CSC (CSCRES), and not a universal property as previously believed. This is likely to impact upon future approaches to clinical targeting of CSC. Michael's on-going 'CSCRES Target' research aims to identify specific, treatment-resistant CSC in multiple malignancies, and to develop approaches through which these can be targeted in the clinic.
Claudia Gasch, Brendan Ffrench, John O'Leary and Michael F Gallagher, Catching Moving Targets: Cancer Stem Cell Targets, Therapy-Resistance & Considerations for Clinical Targeting, Molecular Cancer, 16, (1), 2017, p43-, Journal Article, PUBLISHED  TARA - Full Text
Sulaiman, G, Cooke A, Ffrench B, Gasch C, Abdullai OA, O'Connor K, Elbaruni S, Blacksheilds G, Spillane C, Keegan H, McEneaney V, Knittel R, Rogers A, Jeffery IB, Doyle B, Bates M, d'Adhemar C, Lee M, Campbell EL, Moynagh P, Higgins DG, O'Toole S, O'Neill L, O'Leary JJ and Gallagher MF. , MyD88 is an essential component of retinoic acid induced differentiation in human pluripotent embryonal carcinoma cells. Cell Death & Differentiation (In Press)., Cell Death and Differentiation, 2017, Journal Article, PUBLISHED  Other
Ffrench B, Gasch, Hokamp K, Spillane C, Blackshields G, Mahgoub TM, Bates M, Kehoe L, Mooney A, Doyle R, Doyle B, O'Donnell D, Gleeson N, Hennessy BT, Stordal B, O'Riain C, Lambkin H, O'Toole S, O'Leary JJ, and Gallagher MF., CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell network. Cell Death & Disease , Cell Death and Disease, 2017, Journal Article, ACCEPTED  TARA - Full Text
MacDonagh L, Gallagher MF, Ffrench B, Gasch C et al, Targeting aldehyde dehygrogenase 1 (ALDH1) to circumvent cisplatin resistance in NSCLC, OncoTarget, 2017, Journal Article, PUBLISHED  TARA - Full Text
Lynham-Lennon N, Heavey S, Sommerville G, Bibby B, Ffrench B, Quinn J, Gasch C, O'Leary JJ, Gallagher MF, Reynolds J and Maher S, microRNA-17 is downregulated in esophageal adenocarcinoma cancer stem cells and promotes a radioresistant phenotype, OncoTarget, 8, (7), 2017, p11400 - 11413, Journal Article, PUBLISHED  TARA - Full Text
Cancer stem cells: targeting the sub-populations with epigenetic agents. in, editor(s)Steven Gray , Epigenetic Cancer Therapy, Elsevier, 2015, [Brendan Ffrench, John O'Leary and Michael F Gallagher], Book Chapter, PUBLISHED
McEvoy, L.M., O'Toole, S.A., Spillane, C.D., Martin, C.M., Gallagher, M.F., Stordal, B., Blackshields, G., Sheils, O., O'Leary, J.J., Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer, BMC Cancer, 15, (1), 2015, p547-, Journal Article, PUBLISHED  TARA - Full Text  DOI
Gallagher MF, Salley V, Spillane C, Ffrench B, Martin C, Sheils O, Watson W and O'Leary JJ. , Regulation of Cell Cycle and Suppression of Osteoblast Differentiation Mechanisms by Prostate Cancer Stem-Like Holoclones, Journal of Clinical Pathology, 1, 2015, p11-, Journal Article, PUBLISHED
Ffrench B, Gasch C, O'Leary JJ, Gallagher MF, Developing ovarian cancer stem cell models: laying the pipeline from discovery to clinical intervention., Molecular cancer, 13, 2014, p262 , Journal Article, PUBLISHED  TARA - Full Text  DOI
d'Adhemar CJ, Spillane CD, Gallagher MF, Bates M, Costello KM, Barry-O'Crowley J, Haley K, Kernan N, Murphy C, Smyth PC, O'Byrne K, Pennington S, Cooke AA, Ffrench B, Martin CM, O'Donnell D, Hennessy B, Stordal B, Finn S, McCann A, Gleeson N, D'Arcy T, Flood B, O'Neill LA, Sheils O, O'Toole S, O'Leary JJ, The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer., PloS one, 9, (6), 2014, pe100816 , Journal Article, PUBLISHED  TARA - Full Text  DOI
  

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Award Date
Project Licence Holder, LAST Ireland (Animal Research) 2011-Present
Guest Lecturer (Stem & Cancer Stem Cell Biology), Maynooth University 2014
1. Towards Clinical Targeting of Cancer Stem Cell Treatment-Resistance. It is widely believed that clinical targeting of tumour-initiating, treatment-resistant 'Cancer Stem Cells' (CSCs) can dramatically reduce mortality rates associated with malignancy. Before this can be achieved, the treatment-resistant properties of CSCs must be understood. In my early career I became the first cancer researcher to demonstrate that chemotherapy-resistance is the property of specific types of CSC within the tumour and not a universal CSC property as previously believed (Ffrench et al 2017, MacDonagh et al 2017). Having demonstrated this in two very different malignancies (ovary, [Ffrench et al 2017], and Lung [MacDonagh et al 2017]), it seems likely that similar observations will be reported in other malignancies. For the first time, these studies highlight that CSC therapy-resistance must be targeted by specific, rather than global, therapies. The importance of these findings is reflected in the recent acceptance of the study by the prestigious Nature journal 'Cell Death & Differentiation', and the inclusion of my article reviewing this (Gasch et al 2017) in the 'CSC Special Series' by the highly topical journal 'Molecular Cancer'. In the short time since its publication, the article has been accessed more than 650 times and included in the popular 'CSC News' website's newsletter (3000 subscribers). As an illustration of the importance of this work, this review highlights that the treatment-resistant component of the tumour expands during recurrence and, as such, requires a different approach to treatment. This radically changes our understanding of how CSC should be targeted. It is rewarding that my work, and TCD's support, will be recognised as this field develops in future and patients hopefully receive new, effective treatments. My on-going career aims to identify specific treatment-resistance CSCs in multiple malignancies, and to develop an approach through which these can be targeted in the clinic. 2. Controlling Differentiation of Human Pluripotency. While at TCD I have made an additional breakthrough through my characterisation of the role of key inflammation regulator 'MyD88' in the highly topical area of human pluripotency (Sulaiman et al 2017). This project, which allowed collaboration with Professor Luke O'Neil (School of Biochemistry, TCD) and one of the pioneers of Stem & Cancer Stem Cell research Professor Peter Andrews (University of Sheffield), demonstrated that key 'Differentiation Gatekeepers' such as MyD88 control the initial steps in the differentiation of at least some types of human pluripotent cells. As these pluripotent cells can differentiate to become any cell type within the body, the findings are of immense potential importance for regenerative medicine. In addition, as CSCs can no longer produce tumours when differentiated, this finding can hopefully be exploited as a novel cancer therapy. While this study is still In Press and as yet not yet widely reported, its importance is reflected in its acceptance by the prestigious Nature publication 'Cell Death and Differentiation'.