Trinity College Dublin

Skip to main content.

Top Level TCD Links

Stephen Maher
Ussher Assistant Professor, Surgery

Biography

Stephen Maher graduated from RCSI in 2004 with a PhD in Oncology. Having spent 3 years as a visiting fellow at the National Cancer Institute in the USA, in 2007 he returned to Ireland and the Department of Surgery at Trinity College Dublin, St. James's Hospital as a research fellow. In 2010 he established his on group having secured an Irish Cancer Society Fellowship and HRB project grants in 2011 and 2012, all in the area of radiation research. In 2012 Stephen moved to the University of Hull and Hull York Medical School as a senior lecturer where he lead the Cancer Biology and Therapeutics lab. During his time at Hull he gained substantial teaching experience and qualifications, and is a fellow of the UK Higher Education Academy. Subsequently he developed and directed the MSc in Translational Oncology at Hull, as well as undergraduate cancer biology teaching. Additionally, he acquired funding for and established an optical imaging and radiotherapy core at the University of Hull, and aided in establishing the local tumour biobank for translational cancer studies. He has successfully supervised 5 PhD students and has mentored several postdoctoral researchers. He has secured in excess of €1.5m in competitive research funding, and is well published in the field of microRNA, oesophageal cancer and therapeutics research. In 2016 Stephen returned to TCD as the Ussher Assistant Professor in Translational Oncology, Radiation Therapy and Chemotherapy. Here he leads programmes in translational cancer research, focusing on radiotherapy, radiobiology and chemotherapy. He has recently established new hypoxia and radiotherapy research cores at the recently opened Trinity Translational Medicine Institute. Stephen teaches various aspects of cell and cancer biology and therapy across TCD's MSc Translational Oncology and Molecular Medicine.

Publications and Further Research Outputs

Peer-Reviewed Publications

Lynam-Lennon N, Heavey S, Sommerville G, Bibby BA, Ffrench B, Quinn J, Gasch C, O'Leary JJ, Gallagher MF, Reynolds JV, Maher SG, MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype, Oncotarget, 8, (7), 2017, p11400 - 11413 Journal Article, 2017

MicroRNA in oncogenesis in, editor(s)Trygve Tollefsbol , Epigenetics in Human Disease, London, Elsevier, 2017, [Maher SG, Lynam-Lennon N] Book Chapter, 2017

Bibby BA, Cawthorne C, Lynam-Lennon N, Moody HL, Reynolds JV, Maher SG, Silencing of microRNA-300-5p upregulates MMP1 expression and promotes an invasive phenotype in oesophageal adenocarcinoma, British Journal of Cancer, 2017 Journal Article, 2017

Moody HL, Lind MJ, Maher SG, MicroRNA-31 regulates chemosensitivity in malignant pleural mesothelioma, Molecular Therapy - Nucleic Acids, 2017 Journal Article, 2017

Lynam-Lennon N., Bibby B., Mongan A., Marignol L., Paxton C., Geiersbach K., Geiersbach K., Bronner M., Bronner M., O"Sullivan J., Reynolds J., Maher S., Maher S., Low MiR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma, Molecular Medicine, 22, 2016, p388-397 Journal Article, 2016 DOI

Moore C, Wood T, Cawthorne C, Hilton K, Maher SG, Saunderson J, Archibald SJ, Beavis AW, A method to calibrate the RS2000 X-ray biological irradiator for radiobiological flank irradiation of mice, Biomedical Physics and Engineering Express, 2, 2016, p037001 Journal Article, 2016

Mongan AM, Lynam-Lennon N, Casey R, Maher SG, Pidgeon GP, Reynolds JV, O'Sullivan J, Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma, Clinical Translational Oncology, 18, 2016, p632 - 640 Journal Article, 2016

Bibby B.A.S, Reynolds J.V, Maher S.G, MicroRNA-330-5p as a putative modulator of neoadjuvant chemoradiotherapy sensitivity in oesophageal adenocarcinoma, PLoS ONE, 10, (7), 2015, p013418- Journal Article, 2015 TARA - Full Text URL DOI

MicroRNA and cancer in, editor(s)Steven G Gray , Epigenetic cancer therapy, London, Elsevier, 2015, pp67 - 90, [Maher SG, Bibby B, Moody H, Reid G] Book Chapter, 2015

Lynam-Lennon N, Maher SG, Maguire A, Phelan J, Reynolds JV, O'Sullivan J, Dysfunctional mitochondria and enhanced metabolic plasticity is associated with a radioresistant phenotype in oesophageal adenocarcinoma, PLoS ONE, 9, 2014, pe100738 Journal Article, 2014

Gijsbert J. Hotte, Niamh Lynam-Lennon, John V. Reynolds, Stephen G. Maher, Radiation sensitivity of oesophageal adenocarcinoma: The contribution of the RNA-binding protein RNPC1 and p21-mediated cell cycle arrest to radioresistance, Radiation Research, 177, (3), 2012, p272 - 279 Journal Article, 2012

Picardo SL, Maher SG, O'Sullivan JN, Reynolds JV, Barrett's to oesophageal cancer sequence: a model of inflammatory-driven upper gastrointestinal cancer., Digestive surgery, 29, (3), 2012, p251-60 Journal Article, 2012 DOI

Niamh Lynam-Lennon, John V. Reynolds, Laure Marignol, Orla M Sheils, Graham P. Pidgeon, Stephen G. Maher, microRNA-31 modulates tumor sensitivity to radiation in esophageal cancer through the regulation of DNA repair genes, Journal of Molecular Medicine, 90, 2012, p1449 - 1458 Journal Article, 2012

microRNA in Oncogenesis in, editor(s)Trygve Tollefsbol , Epigenetics in Human Disease, Elsevier, 2012, pp89 - 110, [Niamh Lynam-Lennon, Steven G. Gray, Stephen G. Maher] Book Chapter, 2012

Stephen G. Maher, Dermot T. McDowell, Ben C. Collins, Cian Muldoon, William M. Gallagher, John V. Reynolds, Serum proteomic profiling reveals that pre-treatment complement protein levels are predictive of esophageal cancer patient response to neo-adjuvant chemoradiation, Annals of Surgery, 254, (5), 2011, p809 - 817 Journal Article, 2011

Maher SG, Reynolds JV, Basic concepts of inflammation and its role in carcinogenesis., Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, 185, 2011, p1-34 Journal Article, 2011 DOI

Basic concepts of inflammation and its role in carcinogenesis in, editor(s)Janusz A. Jankowski , Inflammation and Gastrointestinal Carcinogenesis, Springer, 2011, pp1 - 34, [Stephen G. Maher, John V. Reynolds] Book Chapter, 2011

Lynam-Lennon N, Reynolds JV, Pidgeon GP, Lysaght J, Marignol L, Maher SG, Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma., Radiation research, 174, (6), 2010, p703 - 711 Journal Article, 2010 DOI

Byrne M, Reynolds JV, O'Donnell JS, Keogan M, White B, Byrne M, Murphy S, Maher SG, Pidgeon GP, Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery., British Journal of Cancer, 102, (1), 2010, p73-9 Journal Article, 2010 TARA - Full Text DOI

Miriam Byrne, John V. Reynolds, James S. O'Donnell, Mary Keogan, Barry White, Mary Byrne, Seamas Murphy, Stephen G. Maher, Graham P. Pidgeon, Activation of the procoagulant response following neoadjuvant chemotherapy and radiation therapy, and long-term activation following major cancer surgery., British Journal of Cancer, 102, (1), 2010, p73 - 79 Journal Article, 2010

Catriona H. Miller, Stephen G. Maher, Howard A. Young, Cytokine therapies: clinical applications of interferon-gamma, Annals of the New York Academy of Sciences, 1182, 2009, p69 - 79 Journal Article, 2009

Niamh Lynam-Lennon, Stephen G. Maher, John V. Reynolds, The Roles of microRNA in Cancer and Apoptosis, Biological Reviews, 84, (1), 2009, p55 - 71 Journal Article, 2009

Stephen G. Maher, Charles M. Gillham, Shane P. Duggan, Paul C. Smyth, Nicola Miller, Cian Muldoon, Kenneth J. O'Byrne, Orla M. Sheils, Donal Hollywood, John V. Reynolds, Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer., Annals of surgery, 250, (5), 2009, p729-37 Journal Article, 2009 DOI

Dermot T. McDowell, Fraser M. Smith, John V. Reynolds, Stephen G. Maher, C. Adida, P. Crotty, Eoin F. Gaffney, Donal Hollywood, B. Mehigan, R. B. Stephens, Michael J. Kennedy., Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer., International Journal of Colorectal Disease, 24, (11), 2009, p1261 - 1269 Journal Article, 2009

Stephen G. Maher, Charles M. Gillham, Shane P. Duggan, Paul C. Smyth, Nicola Miller, Cian Muldoon, Kenneth J. O'Byrne, Orla M. Sheils, Donal Hollywood, John V. Reynolds, Gene expression microarray analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of oesophageal cancer, Annals of Surgery, 250, (5), 2009, p729 - 737 Journal Article, 2009

Stephen G. Maher, Faruk Sheikh, Anthony J. Scarzello, Ana L. Romero-Weaver, Darren P. Baker, Raymond P. Donnelly, Ana M. Gamero, IFN-alpha and IFN-lambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity, Cancer Biology and Therapy, 7, (7), 2008, p1109 - 1115 Journal Article, 2008

Interferon-gamma in, editor(s)Alexander Zdanov , Class II Cytokines, Kerala, India, Transworld Research Network, Research Signpost, 2008, pp51 - 106, [Howard A. Young, Ana L. Romero-Weaver, Ram Savan, Stephen G. Maher, Jonathan M. Weiss] Book Chapter, 2008

Stephen G. Maher, Ana L. Romero-Weaver, Anthony J. Scarzello, Ana M. Gamero, Interferon: Cellular Executioner or White Knight?, Current Medicinal Chemistry, 14, 2007, p1279 - 1289 Journal Article, 2007

Anthony J. Scarzello, Ana L. Romero-Weaver, Stephen G. Maher, Timothy D. Veenstra, Ming Zhou, Angel Qin, Raymond P. Donnelly, Faruk Sheikh, Ana M. Gamero, A Mutation in the SH2 Domain of STAT2 Prolongs Tyrosine Phosphorylation of STAT1 and Promotes Type-I IFN-induced Apoptosis, Molecular Biology of the Cell, 18, 2007, p2455 - 2462 Journal Article, 2007

Stephen G. Maher, Claire M. Condron, David J. Bouchier-Hayes, Deirdre M. Toomey, Taurine attenuates CD3/Interleukin-2-induced T cell Apoptosis in an in vitro model of Activation-Induced Cell Death (AICD), Clinical and Experimental Immunology, 139, 2005, p279 - 286 Journal Article, 2005

Stephen G. Maher, Deirdre M. Toomey, Claire M. Condron, David J. Bouchier-Hayes, Activation-induced Cell Death: The Controversial Role of Fas and Fas Ligand in Immune Privilege and Tumour Counterattack, Immunology and Cell Biology, 80, 2002, p131 - 137 Journal Article, 2002

Non-Peer-Reviewed Publications

Cawthorne C, Maher SG, Ahmed N, Beavis AW, Improving the application of PET to radiotherapy via preclinical research: status and potential, RAD Magazine, 42, (492), 2016, p29 - 30 Review Article, 2016

Maher SG, Reynolds JV, Oesophageal cancer: The potential of modern molecular tools in treatment, Cancer Professional, 6, 2012, p21 - 25 Review Article, 2012

Research Expertise

Projects

  • Title
    • The role of microRNA and random mitochondrial DNA mutations in a novel clinically-relevant isogenic model of radioresistance in oesophageal adenocarcinoma
  • Summary
    • Oesophageal cancer has one of the worst prognoses for patients of all cancers, and its occurrence is increasing faster than that of any other disease in Ireland. The current treatment for this disease involves a combination of chemotherapy and radiation therapy (neo-CRT) before surgery. However, tumour resistance to radiation therapy remains a significant problem. Our group recently developed a cell model that has been found to reflect radioresistance in oesophageal adenocarcinoma patients. Our preliminary analysis of this model identified certain molecular features as contributing to the radioresistance. Importantly, a number of these differences were authenticated in patient samples, demonstrating clinical utility of the model. The aim of this study is to further explore this model by; firstly, profiling the miRNA compartment to identify those miRNA candidates likely to be involved in the radioresistant phenotype. miRNA are tiny pieces of genetic information that regulate cell function. We will assess the contributions of key miRNA by determining their effects on altering cell sensitivity to radiation, DNA damage induction and repair, DNA repair gene expression, ROS and associated antioxidant levels, which are all linked to radioresistance in our model. Secondly, given the close proximity of the mitochondrial genome to the ROS production site and the low proficiency of mitochondrial DNA repair mechanisms, we aim to examine the contribution of mitochondrial genome instability to radioresistance. This will be accomplished by assessing the levels of mitochondrial mutations using a new random assay and correlating our findings with the radioresistance. Importantly, we will assess radioresistance-associated miRNA and mitochondrial mutations in pre-treatment tumour samples from patients and compare with downstream responses to neo-CRT and survival. Understanding the mechanisms of, and identifying cellular features predictive of radioresistance for oesophageal adenocarcinoma will aid doctors selecting the right patients for neo-CRT, ultimately improving treatment efficacy and patient survival.
  • Funding Agency
    • Health Research Board
  • Date From
    • Oct 2011
  • Date To
    • Sept 2013
  • Title
    • Tissue and Serum microRNA signatures for predicting response to chemoradiotherapy for oesophageal adenocarcinoma
  • Summary
    • Oesophageal cancer is increasing in incidence and has one of the worst prognoses of all cancers. Current therapeutic regimens tend toward neoadjuvant chemoradiotherapy (neo-CRT), for which less then 25% of patients respond. Presently, there are no reports describing miRNA signatures for predicting response to neo-CRT in oesophageal cancer. Studies to determine molecular predictors of response to chemoradiotherapy are essential to improve patient selection and therapeutic efficacy. This study aims to examine, by microarray, the differential expression of miRNA in both matched oesophageal tumour tissue and serum samples from responders and non-responders to neo-CRT. The miRNA data will be applied to a software-based predictive algorithm, establishing a miRNA signature of response. This predictive model will be used to validate the tumour and serum miRNA signature in an independent cohort of patients. Additionally, the miRNA data will be combined with existing gene expression data from a predictive signature previously generated in our lab, establishing a more refined miRNA-gene expression signature for neo-CRT responders and non-responders. Functionally, the relative contributions of specific signature miRNAs to chemo- and radio-sensitivity will be assessed using isogenic cell lines models of chemo- and radio-resistance. This will be achieved using a state-of-the-art miRNA cloning and manipulation strategy. This work has important implications for oesophageal cancer therapy, in that the identification of gene and miRNA signatures predicting patient response to treatment will provide a platform for the development of a new diagnostic test, ultimately improving patient selection, treatment benefit, and survival.
  • Funding Agency
    • Irish Cancer Society
  • Date From
    • Oct 2010
  • Date To
    • Sept 2013
  • Title
    • The role of the chemokine CCL28 (MEC) in oesophageal adenocarcinoma progression: interaction between the immune system and the tumour
  • Summary
    • Previous work in our laboratory has identified a gene 'signature' that predicts, with a high level of accuracy, oesophageal cancer patients who will respond to pre-surgical chemoradiation therapy (CRT). Embedded within this signature are a number of genes that are immune-related. One gene, CCL28, was shown to be expressed at significantly higher levels in tumour tissue from CRT non-responders, compared with responder tumour tissue. CCL28 is a chemokine that displays chemotactic activity for CCR10-expressing T cells and CCR3-expressing eosinophils. These cells are important mediators of inflammation in oesophageal cancer. CCL28 is not normally expressed in the oesophagus, but is preferentially expressed by columnar epithelial cells, such as those found in the colon, salivary gland, mammary gland, trachea, and lung. CCL28 expression can be increased by pro-inflammatory cytokines, such as IL-1B and TNF-a, which can be induced by bile acids; this implies a role for CCL28 in effector cell recruitment to sites of refluxate-induced epithelial injury. We propose that CCL28 expression increases as normal oesophageal tissue progresses through the Barrett's metaplasia-dysplasia-adenocarcinoma sequence, which occurs through chronic exposure to refluxate. In this study, we will examine the relationship between IL-1B, TNF-a, and CCL28 expression in response to bile acids in normal, Barrett's, and oesophageal adenocarcinoma cell lines and tissue explants. Furthermore, using chemotactic assays we will examine the subpopulations of T cells and eosinophils recruited in response to CCL28. Using tissue microarrays, we will examine CCR3- and CCR10-expressing immune infiltrates and correlate these with disease status and tumour response to chemoradiation.
  • Funding Agency
    • Irish Cancer Society
  • Date From
    • Oct 2010
  • Date To
    • Sept 2013

Keywords

Angiogenesis; Apoptosis; Apoptosis, molecular control; Autoimmune and hypersensitivity diseases; Autoimmunity; Bioinformatics; Breast cancer; Cancer genetics and cell biology including metastasis; Cell cycle control; Cell Death; Cellular, molecular and developmental immunology; Chronic Disease; Chronic inflamation; Coagulation biochemistry and disorders; Cytokines, Nitric Oxide; Cytoskelton, cell division; DNA transcription and translation; Gene targeting in breast cancer; Gene therapy; Gene transcription in human cancer; General surgery, upper GI, colorectal and breast; Genetic/Molecular epidemiology; Genomics; Haemotology; Human genetics; Immune system; Immunoassays; Immunochemistry and immunogenetics; Immunological response to surgical trauma; Immunotherapies; Immunotherapies for Cancer; Inflammation and coagulation syndromes; Inflammatory bowel disease; Innate immunology; Intra and intercellular signalling; Leukemias and lymphomas; Leukocyte Biology; Mammilian and human genetics and genomics; Membrane and protein trafficking; Mucosal immunology; Oesophageal cancer; Oesophageal, gastric, intestinal and pancreatic diseases; Oncogenes, apoptosis and tumour development; Protein processing, stability and regulation; Protein sequence, function and expression; Quantitative and molecular genetics; Radiotherapy; Radiotherapy, Biological response modifiers and chemoprevention; Regulatory methods of gene expression; RNA processing, stability and degradation; Stem Cell biology and hematopoiesis; Therapeutic and Clinical oncology; Therapeutic radiography; Tumour immunology and immunotherapy; Vascular Biology, Thrombosis

Recognition

Awards and Honours

iMig Young Investigator Award (Supervisor) 2016

Researcher of the Year, Hull York Medical School (Supervisor) 2016

NCRI Hamilton-Fairley Young Investigator Awards (double-shortlisting) (Supervisor) 2015

1st Prize, Best Research Paper, 12th Annual International Medical Postgraduate Conference, Charles University in Prague (Supervisor) 2015

1st Prize, Best Poster, UK Radiation Oncology (UKRO) Annual Meeting (Supervisor) 2015

1st Prize, Best Research Paper, 11th Annual International Medical Postgraduate Conference, Charles University in Prague (Supervisor) 2014

Biochemical Society Summer Studentship (Supervisor) 2013

Researcher of the Year, Irish Cancer Society 2013

Patey Prize, SARS Annual Meeting 2011

Fellowship, Irish Cancer Society 2010

Roche Researcher of the Year, TCD (Supervisor) 2010

Poster Prize, 7th International Cancer Conference (Dublin) 2009

First Prize, TCD Molecular Medicine Entrepreneurship Course 2009

Travel Award, St. James's Hospital Dublin 2009

Donald Weir Medal for Research, Trinity College Dublin 2008

Oncology Scholars Travel Award, Irish Cancer Society 2008

Fellowship, National Cancer Institute (USA) 2004

Irish Representative at 39th LIYSF 1997

Memberships

Irish Association of Radiation Research (IRRS) 2016 – Present

Association of Radiation Research (UK) 2015 – Present

Biochemical Society UK 2013 – Present

Clinical Trials Ireland (formerly ICORG) 2009 – present

British Association of Cancer Research (BACR) 2013 – Present

European Association of Cancer Research (EACR) 2009 – Present

Irish Association of Cancer Research (IACR) 2008 – Present

American Association of Cancer Research (AACR): Associate Member 2006 – Present

British Lung Foundation 2013 – 2016

International Society for Interferon and Cytokine Research (ISICR) 2004 – 2009


Last updated 23 November 2016 Surgery - Web Administrator (Email).