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Dr. Tony Mc Elligott
Assistant Prof in Molecular Haematology, Haematology
Assistant Prof in Molecular Haematology, Molecular Medicine Ireland

Biography

I am a graduate of University College Cork with a BSc(Hons) in Biochemistry. Following a number of years as a Research Assistant in the University of Ulster at Coleraine, working in the area of molecular analysis of pathogenic bacteria, I undertook a PhD under the supervision of Dr Hugh McGlynn in the area of cancer cell invasion and metastasis. A Research Fellow (post-doc) position with Dr Richie Porter in the area of mitochondrial bioenergetics brought me to Trinity College Dublin in 1999 and I have remained here ever since. I joined the laboratory of Prof Mark Lawlor in 2001 and have subsequently built a research career focusing on the molecular basis of blood cancer and development of novel therapies.

Publications and Further Research Outputs

Peer-Reviewed Publications

McElligott, AM, Maginn, EN, Greene, LM, McGuckin, S, Hayat, A, Browne, PV, Butini, S, Campiani, G, Catherwood, MA, Vandenberghe, E, Williams, DC, Zisterer, DM, Lawler, M, The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia., Cancer Research, 69, (21), 2009, p8366 - 8375 Journal Article, 2009 DOI

Maginn EN, Browne PV, Hayden P, Vandenberghe E, McDonagh B, Evans P, Goodyer M, Tewari P, Campiani G, Butini S, Williams DC, Zisterer DM, Lawler MP, McElligott AM., PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells., British Journal of Cancer, 104, (2), 2011, p281 - 289 Journal Article, 2011 DOI

Lysaght J, Verma NK, Maginn EN, Ryan JM, Campiani G, Zisterer DM, Williams DC, Browne PV, Lawler MP, McElligott AM., The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells, International Journal of Oncology, 42, (1), 2013, p239 - 249 Journal Article, 2013 TARA - Full Text DOI

Sarah Brophy , Fiona M Quinn, David O'Brien, Paul Browne, Elisabeth A. Vandenberghe , Anthony M. McElligott, The Regulation of STAT3 and Its Role in the Adhesion and Migration of Chronic Lymphocytic Leukaemia Cells, Blood, American Society of Hematology Annual Meeting, San Diego, CA, USA, 3-6, December, 201, 128, (22), American Society of Hematology, 2016, pp4347- Poster, 2016 URL

Laura Christine Kickham, Anthony M McElligott, Adriele Prina-Mello, Elisabeth A Vandenberghe, Yuri Volkov, Paul Browne, Interrogating the Interaction of CD52 Functionalised Metallic Nanoparticles with Malignant B Lymphocytes , Blood, 126 , (23 ), 2015 Journal Article, 2015 URL

Anthony M McElligott , Eamon P Breen , Ruth Cleary , Sarah Brophy, Fiona McCarthy , Emma Heffernan , Vincent O'Mahony , Nicola Gardiner , Derek G Doherty, Bridgette Byrne , Paul V Browne , Catherine M Flynn, , Characterisation of Naive Immunological Profile of Umbilical Cord Blood: The Role of Mucosal-Associated Invariant T Cells and Functional Defects of T Cells and Natural Killer Cells, Blood, American Society of Hematology, San Diego, CA, USA, 1-4 Dec, 2018, 130, (1), American Society of Hematology, 2017, pp3590- Poster, 2017 DOI

Ghnewa YG, O'Reilly VP, Vandenberghe E, Browne PV, McElligott AM, Doherty DG, Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8+ invariant natural killer T cells, Clinical Immunology, 183, 2017, p91 - 98 Journal Article, 2017 URL

S A Bright, A M McElligott, J W O'Connell, L O'Connor, P Carroll, G Campiani, M W Deininger, E Conneally, M Lawler, D C Williams, and D.M Zisterer, Novel pyrrolo-1,5-benzoxazepine compounds display significant activity against resistant chronic myeloid leukaemia cells in vitro, in ex vivo patient samples and in vivo , British Journal of Cancer, 102, 2010, p1474 - 1482 Journal Article, 2010 TARA - Full Text

Greene LM, Nathwani SM, Bright SA, Fayne D, Croke A, Gargliardi M, Mc Elligott AM, O'Connor L, Carr M, Keely NO, O'Boyle NM, Carroll P, Sarkadi B, Conneally E, Lloyd DG, Lawler M, Meegan MJ, Zisterer DM, The vascular targeting agent Combretastatin-A4 and a novel cis-restricted {beta}-lactam analogue CA-432 induce apoptosis in human chronic myeloid leukemia cells and in ex vivo patient samples including those displaying multidrug resistance., The Journal of Pharmacology and Experimental Therapeutics, 335, (2), 2010, p302 - 313 Journal Article, 2010 DOI

Langabeer SE, Quinn F, O'Brien D, McElligott AM, Kelly J, Browne PV, Vandenberghe E, Incidence of the BRAF V600E mutation in chronic lymphocytic leukaemia and prolymphocytic leukaemia, Leukemia Research, 36, (4), 2012, p483 - 484 Journal Article, 2012

Langabeer S, O'Brien D, McElligott AM, Lavin M, Browne P, BRAF V600E-negative hairy cell leukaemia, Case Reports in Hematology, 2013 Journal Article, 2013 DOI TARA - Full Text

Verma, NK, Dempsey, E, Conroy, J, Olwell, P, McElligott, AM, Davies, AM, Kelleher, D, Butini, S, Campiani, G, Williams, DC, Zisterer, DM, Lawler, M, Volkov, Y, A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin., Journal of Molecular Medicine , 86, (4), 2008, p457- 469 Journal Article, 2008 DOI TARA - Full Text

Forde JC., Maginn EN., McNamara G., Martin LM., Campiani GC. , Williams DC, Zisterer D.M, McElligott AM., Lawler M, , Lynch TH, Hollywood D., Marignol L, Microtubule-Targeting-Compound PBOX-15 Radiosensitizes Cancer Cells In Vitro , Cancer Biology and Therapy, 11, (4), 2011, p6 - 13 Journal Article, 2011

Cunningham, O, McElligott, AM, Carroll, AM, Breen, E, Reguenga, C, Oliveira, ME, Azevedo, JE, Porter, RK, Selective detection of UCP 3 expression in skeletal muscle: effect of thyroid status and temperature acclimation., Biochimica et biophysica acta, 1604, (3), 2003 Journal Article, 2003

Reid, HM, McElligott, AM, McGlynn, H, Phenotypic alterations in Caki-1 cells as a consequence of TIMP-1 overexpression., Cancer letters, 169, (2), 2001 Journal Article, 2001

Bright S.A, Byrne A.J, Vandenberghe E, Browne P.V, McElligott A.M, Meegan M.J, Williams D.C, Selected nitrostyrene compounds demonstrate potent activity in chronic lymphocytic leukaemia cells, including those with poor prognostic markers, Oncology Reports, 41, (5), 2019, p3127 - 3136 Journal Article, 2019 URL DOI

AM McElligott et al, Matrix metalloproteinase and tissue inhibitor of metalloproteinase regulation of the invasive potential of a metastatic renal cell line, Biochemical Society Transactions, 25, 1997, p147- Journal Article, 1997

Tissue Inhibitor of Metalloproteinase Expression in, editor(s)Walden P., Trefzer U., Sterry W., Farzaneh F., Zambon P. , Gene Therapy of Cancer. Advances in Experimental Medicine and Biology, Boston, MA, USA, Springer, 1998, pp73 - 77, [A. M. McElligot, tA. H. Baker, H. McGlynn] Book Chapter, 1998

Anthony Davies, Anthony McElligott, Graham Pidgeon, Anthony Ryan, Ruth Foley, Cancer Biology where do we go next?, European Pharmaceutical Review, (1), 2010 Journal Article, 2010

Brophy S et al, Microenvironmental-Mediated Regulation of L-Selectin in Chronic Lymphocytic Leukaemia, Blood, American Society of Hematology Annual Meeting, Orlando, FL, USA, 5-8 December, 2015, 126, (23), American Society of Hematology, 2015, pp4133 - 4133 Poster, 2015 URL

Anthony M. McElligott, Elaina N. Maginn, Lisa M. Greene, Elizabeth Vandenberghe, Amjad Hayat, Margaret M. McGee, Giuseppe Campiani, Paul V. Browne, D. Clive Williams, Daniela M. Zisterer and Mark P. Lawler, Pyrrolo-1,5-benzoxazepines induce apoptosis in chronic B-lymphoid malignancies, Cancer Research, 97th AACR Annual Meeting, Washington DC, USA, 1-5 April, 2006, 66, (8), AACR, 2006, pp899 - 899 Poster, 2006 URL

Research Expertise

Description

I lead the translational research programme of the Discipline of Haematology in the Trinity Translational Medicine Institute (TTMI) at Trinity College Dublin (TCD). This research programme is closely aligned with the Department of Haematology, Cancer Molecular Diagnostics Laboratory and Cryobiology (stem cell) Laboratories in St James's Hospital (SJH) and, as a result, my research is positioned at the intersection of basic, translational and clinical research in blood cancers at SJH and TCD. Highlighting the significance of my research direction is my role as the Scientific Lead of the Blood Cancer Research Programme in the Trinity /St James Cancer Institute. For over 10 years I have been involved in running a biorepository of clinically and molecularly annotated blood cancer patient material (RNA, DNA and cryopreserved cells). This biobank has developed into an all-Ireland resource through involvement with Blood Cancer Network Ireland and allows for high quality clinical and translational research, as well as facilitating collaboration with groups investigating novel therapeutic agents and immunotherapy strategies. My research is multidisciplinary in nature and encompasses the molecular profiling of blood cancer at diagnosis and in response to therapy; molecular analysis of diagnostic and prognostic biomarkers; the investigation of novel therapeutic strategies, including immunotherapy, nanotherapeutics and small molecule therapeutics; and the molecular mediators of leukemic cell homing and trafficking. Current research projects focus on chronic B-cell malignancies, in particular chronic lymphocytic leukaemia and multiple myeloma, the immunomodulatory and molecular aspects of allogeneic stem cell therapy as part of a cellular therapeutic programme.

Projects

  • Title
    • Assessing the functional impact of NOTCH1 mutations in chronic B-cell malignancies
  • Summary
    • Chronic Lymphocytic leukaemia (CLL) is an incurable B-lymphoid malignancy accounting for 38% of leukaemias in the western world. CLL has a variable clinical course due differences in underlying genetic lesions, degree of clonal evolution, activated signalling pathways and interaction with the microenvironment within lymph nodes and the bone marrow. The aim of this project is to assess the functional impact of NOTCH1 mutations in CLL by utilizing in vitro micro-environment models to analyse aberrant signalling pathways in NOTCH1 mutated cells, allowing the determination of potential 'precision medicine' strategies for these patients.
  • Funding Agency
    • Wellcome Trust
  • Date From
    • 01/10/2016
  • Date To
    • 30/09/2021
  • Title
    • 'STAT3 signalling as a therapeutic target in multiple myeloma'
  • Summary
    • Multiple myeloma is a plasma cell malignancy that accounts for around 10% of all haematological cancers. It remains generally incurable, with most patients experiencing relapse after first-line treatment. In the EU, MM incidence is projected to increase from 35,000 new cases per annum to over 43,000 by 2030 whilst deaths due to MM are also projected to increase. Therefore new drugs are urgently required to improve the anti-myeloma arsenal. Aberrant activation of a number of oncogenic signalling pathways in myeloma leads to cell growth and survival, as well as to angiogenesis and to the development of drug resistance. Targeting one or more of these pathways is therefore a promising anti-MM strategy. We have recently designed and synthesized novel guanidinium compounds which have demonstrated anti-tumour activity in myeloma. A lead compound VP79s has been identified and its ability to induce apoptosis and to target oncogenic signalling pathways in MM including the STAT3 pathway has been examined. VP79s potently reduced the viability of drug resistant and sensitive MM cell lines through induction of apoptosis. Importantly, VP79s rapidly inhibited both constitutive and IL-6 induced STAT3 activation and, consequently, decreased expression of STAT3-mediated anti-apoptotic gene products, Mcl-1 and survivin. In conclusion, the novel compound VP79s can target dysregulated STAT3 activation and induce apoptosis in myeloma cells in vitro, suggesting its potential as a novel anti-cancer therapeutic which can overcome tumour microenvironment induced resistance. Identification and development of novel drugs that can target STAT3 remains an important scientific and clinical challenge.
  • Funding Agency
    • Trinity College
  • Date From
    • 01/10/2016
  • Date To
    • 31/03/2020
  • Title
    • Blood Cancer Network Ireland
  • Summary
    • Blood Cancer Network Ireland (BCNI) is a national clinical research network that benefits blood cancer patients in Ireland. BCNI offers early stage clinical trials to blood cancer patients, a biobank of blood cancer patient material and a blood cancer registry. This biobank of clinically and molecularly annotated patient material (RNA, DNA and cryopreserved cells) allows us to perform high quality clinical and translational research and allows us to collaborate with groups investigating novel therapeutic agents and immunotherapy strategies.
  • Funding Agency
    • SFI/Irish Cancer Society
  • Date From
    • 01/06/2015
  • Date To
    • 31/05/2020
  • Title
    • Investigation of the therapeutic potential of secondary metabolites produced by Rasamsonia emersonii.
  • Summary
    • Fungal secondary metabolites represent a diverse array of natural products, and bioactive compounds from these organisms have yielded some of the most important natural products for the pharmaceutical industry. Genome sequencing projects have revealed that fungi are rich in biosynthethic clusters that direct the synthesis of these secondary metabolites. R. emersonii is a thermophilic ascomycete that represents a reservoir of undiscovered bioactive compounds. This project seeks to investigate the therapeutic potential of secondary metabolites isolated from R. emersonii. A two-pronged approach will be adopted, employing functional genomics and a laboratory scale screening programme. Initially, the project is designed as a two year master's programme. However, given the huge diversity and structural types of known fungal secondary metabolites and the fact that more and more are continually being discovered, it is highly likely that R. emersonii will produce an array of secondary metabolite products. Thus, the potential for this project to continue to a PhD programme is extremely promising.
  • Funding Agency
    • IT Sligo
  • Date From
    • 01/10/2019
  • Date To
    • 30/09/2021
  • Title
    • Cancer Biobanking Awareness: Improving Research & Healthcare
  • Summary
    • In recent years, as part of engaging with patients and the public, it has become clear that patients want to know more about the research their samples were used for. Our cancer research community in Trinity College and St. James's Hospital are keen to inform and educate patients who have donated to the biobanks about the research conducted as well as informing cancer patients and the public about the benefits of participation in research, making them more likely to participate in the future. Our proposal is to unite our local biobanks to organise a novel annual cancer biobank awareness day. We are in the process of updating biobank patient information leaflets (PIL) and intend to include a web address for biobank updates and details of ongoing studies as well as details of the annual event. Details about the day will also be advertised in the hospital and an information desk will be set up in the main campus in the weeks running up to the event. Currently we are part of a national biobanking working group and it is hoped to expand this event to a national event in the future.
  • Funding Agency
    • Irish Cancer Society
  • Date From
    • 01/01/2020
  • Date To
    • 31/12/2020

Keywords

Apoptosis; Biology and therapy of myeloma; Drug development and evaluation; Haemotology; Leukemias and lymphomas; Multiple Myeloma

Recognition

Representations

Scientific Secretary of the Haematology Association of Ireland. 2017

Memberships

Irish Association for Cancer Research 1995

Haematology Association of Ireland 2001

American Association for Cancer Research 2004

European Association for Cancer Research 2006