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Dr. Joanne Lysaght
Associate Professor, Surgery

Biography

Dr. Joanne Lysaght graduated with B.Sc.(Hons) in Science from Maynooth University with maths and biology. She then went on to complete a PhD in 2005, in the Department of Biochemistry and Immunology in Trinity College Dublin, in the area of Tumour Immunology. Following completion of her PhD, she worked in the Cancer Molecular Diagnostic Laboratory based in St. James's Hospital and then took up a post-doctoral position in the Department of Haematology and Oncology, TCD, where she worked on a novel family of chemotherapeutic drugs for the treatment of childhood leukemias. Dr. Lysaght then moved to the Department of Surgery, TCD/St. James's Hospital where her research focused on the role of the adaptive immune system in the link between obesity and gastrointestinal cancer. In 2011, Dr. Lysaght was appointed Ussher Assistant Professor in Molecular Oncology, in 2015 she was appointed Assistant Professor in the School of Medicine, TCD and promoted to Associate Professor in 2017 where she continues her research in cancer immunology and immunotherapy.

Dr. Lysaght's research group focus on a number of different areas around the central theme of cancer immunology and immunotherapy. Currently, a major research focus is investigating the impact and scheduling of chemotherapy and radiotherapy, and targeting immunometabolism to enhance anti-tumour immunity when used in combination with immunotherapies, namely immune checkpoint inhibitors. The majority of research in the cancer immunology and immunotherapy group is focused on upper gastrointestinal cancer, particularly oesophageal cancer. Research into how the regulation and trafficking of lymphocytes can be targeted to reduced adipose tissue and liver-associated inflammation is also a research interest within the group. Other areas of interest include identifying novel immunotherapeutic targets in the pre-malignant setting such as Barrett's Oesophagus, which can be used to slow or prevent progression to malignancy. Another research interest is the area of obesity and cancer, and how this impacts anti-tumour immunity. Dr. Lysaght's group also investigates the role of adaptive immunity and obesity in the debilitating cancer-associated wasting disease cachexia and sarcopenia.

Publications and Further Research Outputs

Peer-Reviewed Publications

Donlon, N.E. and Power, R. and Hayes, C. and Davern, M. and Reynolds, J.V. and Lysaght, J., Radiation and immunotherapy in upper gastrointestinal cancers: The current state of play, International Journal of Molecular Sciences, 22, (3), 2021, p1-15 Journal Article, 2021 TARA - Full Text DOI

Donlon, N.E. and Power, R. and Hayes, C. and Reynolds, J.V. and Lysaght, J., Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity, Cancer Letters, 502, 2021, p84-96 Journal Article, 2021 DOI TARA - Full Text

CX3CL1 Signaling in the Tumor Microenvironment in, Advances in Experimental Medicine and Biology , 2020, pp1 - 12, [Conroy, M.J. and Lysaght, J.] Book Chapter, 2020 DOI

Royds J, Cassidy H, Conroy MJ, Dunne MR, Matallanas D, Lysaght J, McCrory C., An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study., Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020 Journal Article, 2020 DOI

Melo AM, Maher SG, O'Leary SM, Doherty DG, Lysaght J, Selective effects of radiotherapy on viability and function of invariant natural killer T cells in vitro, Radiotherapy and Oncology, 145, 2020, p128 - 136 Journal Article, 2020

Morrissey ME, Byrne R, Nulty C, McCabe NH, Lynam-Lennon N, Butler CT, Kennedy S, O'Toole D, Larkin J, McCormick P, Mehigan B, Cathcart MC, Lysaght J, Reynolds JV, Ryan EJ, Dunne MR, O'Sullivan J., The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation., BMC Cancer, 20, (1), 2020, p566 Journal Article, 2020 DOI TARA - Full Text

Buckley AM, Dunne MR, Morrissey ME, Kennedy SA, Nolan A, Davern M, Foley EK, Clarke N, Lysaght J, Ravi N, O'Toole D, MacCarthy F, Reynolds JV, Kennedy BN, O'Sullivan J., Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib., Scientific reports, 10, (1), 2020, p12105 Journal Article, 2020 DOI TARA - Full Text

Royds J, Conroy MJ, Dunne MR, Cassidy H, Matallanas D, Lysaght J, McCrory C., Examination and characterisation of burst spinal cord stimulation on cerebrospinal fluid cellular and protein constituents in patient responders with chronic neuropathic pain - A Pilot Study., Journal of neuroimmunology, 344, 2020, p577249 Journal Article, 2020 DOI

Moore D, Galvin D, Conroy MJ, Das B, Dunne M, Lysaght J, McCrory C., Characterisation of the effects of pulsed radio frequency treatment of the dorsal root ganglion on cerebrospinal fluid cellular and peptide constituents in patients with chronic radicular pain: A randomised, triple-blinded, controlled trial., Journal of neuroimmunology, 343, 2020, p577219 Journal Article, 2020 DOI

Cannon, A. and Clarke, N. and MacCarthy, F. and Dunne, C. and Kevans, D. and Mahmud, N. and Lysaght, J. and O'Sullivan, J., Effect of cigarette smoke extract on the intestinal microenvironment of ulcerative colitis tissue, JGH Open, 4, (6), 2020, p1191-1198 Journal Article, 2020 DOI TARA - Full Text

Davern, M. and Lysaght, J., Cooperation between chemotherapy and immunotherapy in gastroesophageal cancers, Cancer Letters, 495, 2020, p89-99 Journal Article, 2020 DOI TARA - Full Text

Melo A.M., Conroy M.J., Foley E.K., Dockry E., Breen E.P., Reynolds J.V., Lysaght J., Doherty D.G., CD1d expression and invariant natural killer T-cell numbers are reduced in patients with upper gastrointestinal cancers and are further impaired by commonly used chemotherapies, Cancer Immunology, Immunotherapy, 69, (6), 2020, p969 - 982, p969-982 Journal Article, 2020 DOI

Noel E. Donlon and Andrew Sheppard and Maria Davern and Fiona O'Connell and James J. Phelan and Robert Power and Timothy Nugent and Kate Dinneen and John Aird and John Greene and Paul Nevins Selvadurai and Anshul Bhardwaj and Emma K. Foley and Narayanasamy Ravi and Claire L. Donohoe and John V. Reynolds and Joanne Lysaght and Jacintha O'Sullivan and Margaret R. Dunne, Linking Circulating Serum Proteins with Clinical Outcomes in Esophageal Adenocarcinoma"An Emerging Role for Chemokines, Cancers, 12, (11), 2020, p3356 Journal Article, 2020 TARA - Full Text

Sheppard, A.D. and Lysaght, J., Immunometabolism and Its Potential to Improve the Current Limitations of Immunotherapy, Methods in Molecular Biology, 2184, 2020, p233-263 Journal Article, 2020 DOI

Lewis, D.E. and Lysaght, J. and Wu, H., Editorial: T cell alterations in adipose tissue during obesity, HIV, and cancer, Frontiers in Immunology, 10, (MAY), 2019 Journal Article, 2019 TARA - Full Text DOI

Hannon, G. and Lysaght, J. and Liptrott, N.J. and Prina-Mello, A., Immunotoxicity Considerations for Next Generation Cancer Nanomedicines, Advanced Science, (1900133), 2019 Journal Article, 2019 DOI TARA - Full Text

Kavanagh, M.E. and Conroy, M.J. and Clarke, N.E. and Gilmartin, N.T. and Feighery, R. and MacCarthy, F. and O†Toole, D. and Ravi, N. and Reynolds, J.V. and O†Sullivan, J. and Lysaght, J., Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma, Cancer Microenvironment, 2019 Journal Article, 2019 DOI

Royds J, Conroy M, Dunne M, Lysaght J, McCrory C, An investigation into the modulation of Tcell phenotypes by amitriptyline and nortriptyline, European Neuropsychopharmacology, 2019 Journal Article, 2019

Joanne Lysaght, The 'obesity paradox' in action with cancer immunotherapy, Nature Reviews Endocrinology, 2019 Journal Article, 2019

MÌnch, N.S. and Fang, H.-Y. and Ingermann, J. and Maurer, H.C. and Anand, A. and Kellner, V. and Sahm, V. and Wiethaler, M. and Baumeister, T. and Wein, F. and EinwÀchter, H. and Bolze, F. and Klingenspor, M. and Haller, D. and Kavanagh, M. and Lysaght, J. and Friedman, R. and Dannenberg, A.J. and Pollak, M. and Holt, P.R. and Muthupalani, S. and Fox, J.G. and Whary, M.T. and Lee, Y. and Ren, T.Y. and Elliot, R. and Fitzgerald, R. and Steiger, K. and Schmid, R.M. and Wang, T.C. and Quante, M., High-Fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett's Esophagus via Interleukin 8 and Alterations to the Gut Microbiome, Gastroenterology, 157, (2), 2019, p492-506.e2 Journal Article, 2019 DOI

Lysaght, J., The â€~obesity paradox†in action with cancer immunotherapy, Nature Reviews Endocrinology, 15, (3), 2019, p132-133 Journal Article, 2019 DOI

Mongan AM, Lynam-Lennon N, Doyle SL, Casey R, Carr E, Cannon A, Conroy MJ, Pidgeon GP, Brennan L, Lysaght J, Reynolds JV, O'Sullivan J., Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma., International journal of medical sciences, 16, (4), 2019, p519-528 Journal Article, 2019 DOI TARA - Full Text

O†sullivan, K.E. and Michielsen, A.J. and O†regan, E. and Cathcart, M.C. and Moore, G. and Breen, E. and Segurado, R. and Reynolds, J.V. and Lysaght, J. and O†sullivan, J., pSTAT3 levels have divergent expression patterns and associations with survival in squamous cell carcinoma and adenocarcinoma of the oesophagus, International Journal of Molecular Sciences, 19, (6), 2018, p1720- Journal Article, 2018 DOI TARA - Full Text

Das, B. and Conroy, M. and Moore, D. and Lysaght, J. and McCrory, C., Human dorsal root ganglion pulsed radiofrequency treatment modulates cerebrospinal fluid lymphocytes and neuroinflammatory markers in chronic radicular pain, Brain, Behavior, and Immunity, 70, 2018, p157-165 Journal Article, 2018 DOI

O†Sullivan, J. and Lysaght, J. and Donohoe, C.L. and Reynolds, J.V., Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments, Nature Reviews Gastroenterology and Hepatology, 15, (11), 2018, p699-714 Journal Article, 2018 DOI

Conroy MJ, Maher SG, Melo AM, Doyle SL, Foley E, Reynolds JV, Long A, Lysaght J., Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8+ T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients., Frontiers in immunology, 9, 2018, p1867 Journal Article, 2018 DOI TARA - Full Text

*Galvin KC, *Conroy MJ, Doyle SL, Dunne MR, Fahey R, Foley E, O'Sullivan KE, Doherty DG, Geoghegan JG, Ravi N, O'Farrelly C, Reynolds JV, Lysaght J., Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma., Cancer Letters, 418, 2018, p230-238 Journal Article, 2018 DOI URL

Melo, A.M. and Zhang, L. and Dockry, E.F. and Petrasca, A. and Ghnewa, Y.G. and Breen, E.P. and Morrissey, M.E. and O'Reilly, C. and Bruen, R. and O'Meara, A. and Lysaght, J. and Zhu, X. and Doherty, D.G., Novel thioglycoside analogs of α-galactosylceramide stimulate cytotoxicity and preferential Th1 cytokine production by human invariant natural killer T cells, Glycobiology, 28, (7), 2018, p512-521 Journal Article, 2018 DOI

Doyle SL, Mongan AM, Donohoe CL, Pidgeon GP, Sherlock M, Reynolds JV, Lysaght J., Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma., Diseases of the Esophagus, 30, (6), 2017, p1 - 11 Journal Article, 2017 DOI

Donohoe C.L, Lysaght J, O'Sullivan J, Reynolds J.V, Emerging Concepts Linking Obesity with the Hallmarks of Cancer, Trends in Endocrinology and Metabolism, 28, (1), 2017, p46 - 62 Journal Article, 2017 URL DOI

Kavanagh ME, Conroy MJ, Clarke NE, Gilmartin NT, O'Sullivan KE, Feighery R, MacCarthy F, O'Toole D, Ravi N, Reynolds JV, O'Sullivan J, Lysaght J, Impact of the inflammatory microenvironment on T-cell phenotype in the progression from reflux oesophagitis to Barrett oesophagus and oesophageal adenocarcinoma., Cancer letters, 370, (1), 2016, p117-24 Journal Article, 2016 DOI

Conroy M.J, Galvin K.C, Kavanagh M.E, Mongan A.M, Doyle S.L, Gilmartin N, O'Farrelly C, Reynolds J.V, Lysaght J, CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer, Immunology and Cell Biology, 94, (6), 2016, p531 - 537 Journal Article, 2016 DOI URL

Conroy M.J, Galvin K.C, Doyle S.L, Kavanagh M.E, Mongan A.-M, Cannon A, Moore G.Y, Reynolds J.V, Lysaght J, Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients, Inflammation, 39, (5), 2016, p1729 - 1736 Journal Article, 2016 URL DOI

Cathcart M.-C, Useckaite Z, Drakeford C, Semik V, Lysaght J, Gately K, O'Byrne K.J, Pidgeon G.P, Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo, BMC Cancer, 16, (1), 2016, p707- Journal Article, 2016 TARA - Full Text URL DOI

Conroy M.J, Fitzgerald V, Doyle S.L, Channon S, Useckaite Z, Gilmartin N, O†Farrelly C, Ravi N, Reynolds J.V, Lysaght J, The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function, Journal of Leukocyte Biology, 100, (6), 2016, p1435 - 1442 Journal Article, 2016 URL DOI

Mockler MB, Conroy MJ, Lysaght J, Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment., Frontiers in oncology, 4, 2014, p107 Journal Article, 2014 DOI TARA - Full Text

Lynam-Lennon N, Connaughton R, Carr E, Mongan AM, O'Farrell NJ, Porter RK, Brennan L, Pidgeon GP, Lysaght J, Reynolds JV, O'Sullivan J., Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma., BMC Cancer, 3, (14), 2014, p907- Journal Article, 2014 TARA - Full Text

Ahearne M, Lysaght J, Lynch AP, Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells., Cell regeneration (London, England), 3, (1), 2014, p13 - 13 Journal Article, 2014 TARA - Full Text DOI

Kavanagh, M.E., O'Sullivan, K.E., O'Hanlon, C., (...), Lysaght, J., Reynolds, J.V., The esophagitis to adenocarcinoma sequence; the role of inflammation, Cancer Letters, 345, (2), 2014, p182-189 Journal Article, 2014 DOI

O'Sullivan KE, Phelan JJ, O'Hanlon C, Lysaght J, O'Sullivan JN, Reynolds JV., The role of inflammation in cancer of the esophagus., Expert Reviews Gastroenterology Hepatology, 8, (7), 2014, p749 - 760 Journal Article, 2014 DOI TARA - Full Text

O'Sullivan KE, Reynolds JV, O'Hanlon C, O'Sullivan JN, Lysaght J, Could signal transducer and activator of transcription 3 be a therapeutic target in obesity-related gastrointestinal malignancy?, Journal of gastrointestinal cancer, 45, (1), 2014, p1-11 Journal Article, 2014 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, p239-46 Journal Article, 2013 DOI

Doyle SL, Bennett AM, Donohoe CL, Mongan AM, Howard JM, Lithander FE, Pidgeon GP, Reynolds JV, Lysaght J, Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research., Nutrition research (New York, N.Y.), 33, (3), 2013, p171-9 Journal Article, 2013 DOI

Allott EH, Lysaght J, Cathcart MC, Donohoe CL, Cummins R, McGarrigle SA, Kay E, Reynolds JV, Pidgeon GP, MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation., Molecular carcinogenesis, 52, (2), 2013, p144-54 Journal Article, 2013 DOI

Allott EH, Morine MJ, Lysaght J, McGarrigle SA, Donohoe CL, Reynolds JV, Roche HM, Pidgeon GP, Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis, Clinical and Translational Gastroenterology, 3, 2012 Journal Article, 2012

Donohoe CL, Doyle SL, McGarrigle S, Cathcart MC, Daly E, O'Grady A, Lysaght J, Pidgeon GP, Reynolds JV., Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma, British Journal of Surgery, 99, (3), 2012, p387-96 Journal Article, 2012 DOI

Allott EH, Oliver E, Lysaght J, Gray SG, Reynolds JV, Roche HM, Pidgeon GP, The SGBS cell strain as a model for the in vitro study of obesity and cancer., Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 14, (10), 2012, p774-82 Journal Article, 2012 DOI

Doyle, S.L. and Donohoe, C.L. and Lysaght, J. and Reynolds, J.V., Visceral obesity, metabolic syndrome, insulin resistance and cancer, Proceedings of the Nutrition Society, 71, (1), 2012, p181-189 Journal Article, 2012 DOI

Doyle SL, Donohoe CL, Lysaght J, Reynolds JV, Viseral obesity, metabolic syndrome, insulin resistance and cancer, Proceedings of the Nutrition Society, 71, (1), 2012, p181-9 Journal Article, 2012 DOI

Allott EH, Lysaght J, Cathcart MC, Donohoe CL, Cummins R, McGarrigle SA, Kay E, Reynolds JV, Pidgeon GP, MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation, Molecular Carcinogenesis, 2012 Journal Article, 2012

Allott EH, Morine MJ, Lysaght J, McGarrigle SA, Donohoe CL, Reynolds JV, Roche HM, Pidgeon GP, Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis., Clinical and translational gastroenterology, 3, 2012, pe12 Journal Article, 2012 DOI TARA - Full Text

SL Doyle, C Donohoe, S Finn, J Howard, FE Lithander, JV Reynolds, G Pidgeon, J Lysaght , IGF-1 and its Receptor in Esophageal Cancer: Association with Adenocarcinoma and Visceral Obesity, American Journal of Gastroenterology, 107, 2012, p196 - 204 Journal Article, 2012 DOI URL

Carroll PA, Healy L, Lysaght J, Boyle T, Reynolds JV, Kennedy MJ, Pidgeon G, Connolly EM., Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer., Molecular Carcinogenesis, 50, (8), 2011, p643 - 651 Journal Article, 2011 DOI

J. Lysaght, E.P. van der Stok, E.H. Allott, R. Casey, C.L. Donohoe, J.M. Howard, S.A. McGarrigle, N. Ravi, J.V. Reynolds, G.P. Pidgeon, Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue, Cancer Letters, 312, (1), 2011, p62-72 Journal Article, 2011 TARA - Full Text

Cathcart MC, Lysaght J, Pidgeon GP, Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention., Cancer metastasis reviews, 30, (3-4), 2011, p363-85 Journal Article, 2011

Lysaght J, Allott EH, Donohoe CL, Howard JM, Pidgeon GP, Reynolds JV., T lymphocyte activation in visceral adipose tissue of patients with oesophageal adenocarcinoma., British Journal of Surgery, 98, (7), 2011, p964 - 974 Journal Article, 2011 DOI

Doyle SL, Lysaght J, Reynolds JV, Obesity and post-operative complications in patients undergoing non-bariatric surgery., Obesity reviews : an official journal of the International Association for the Study of Obesity, 11, (12), 2010, p875-86 Journal Article, 2010

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

Donohoe CL, Pidgeon GP, Lysaght J, Reynolds JV., Obesity and gastrointestinal cancer, British Journal of Surgery, 2010 Journal Article, 2010

Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O'Byrne K, Nie D, Honn KV., Lipoxygenase metabolism: roles in tumor progression and survival., Cancer Metastasis Reviews, 3-4, 2007, p503 - 524 Journal Article, 2007

Lysaght, J., Jarnicki, A. and Mills, K.H.G. , Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumour immunity. , Cancer Immunology and Immunotherapy, Published online Feb, (DOI 10.1007/s00262-0), 2007, p1367 - 1379 Journal Article, 2007 DOI URL

Jarnicki, A.G., Lysaght, J, Todryk, S, Mills, K.H.G, Suppression of antitumor immunity by IL-10 and TGF-b-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells., Journal of Immunology, 177, (2), 2006, p896-904 Journal Article, 2006 URL TARA - Full Text

Lysaght J, Todryk S., Developments in cancer vaccination, Curr Opin Investig Drugs. , 2003 Journal Article, 2003

Casey DG, Lysaght J, James T, Bateman A, Melcher AA, Todryk SM., Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine., Immunology, 110, (1), 2003, p105-11 Journal Article, 2003 URL TARA - Full Text

Research Expertise

Description

Dr. Lysaght's research group focus on a number of different areas around the central theme of tumour immunology and immunotherapy. A major research interest is the area of obesity and cancer, and how this impacts anti-tumour immunity. The majority of research in the tumour immunology group is focused on upper gastrointestinal cancer, particularly oesophageal cancer. Research into how the regulation and trafficking of lymphocytes can be targeted to reduced adipose tissue and liver-associated inflammation is a major theme within the group. Other areas of interest include identifying novel immunotherapeutic targets in the pre-malignant setting such as Barrett's Oesophagus, which can be used to slow or prevent progression to malignancy. We are also currently investigating the impact of chemotherapy and radiotherapy on anti-tumour immunity and immunotherapies. Another area under current investigation is the role of adaptive immunity and obesity in the debilitating cancer-associated wasting disease cachexia and sarcopenia, which is directly responsible for up to 20% of all cancer deaths.

Projects

  • Title
    • Evaluating the role of T cells in the progression of Barrett's Oesophagus to Oesophageal Adenocarcinoma: identification of novel immunotherpeutic targets
  • Summary
    • Barrett's oesophagus (BO) is the pre-malignant link in the progression from reflux oesophagitis to oesophageal adenocarcinoma (OAC), a cancer whose incidence rates are rising rapidly in Ireland. Premalignant conditions that develop in the presence of chronic inflammation are often associated with a dysregulated immune response. The role of T cells in the progression to oesophageal adenocarcinoma is largely unknown, however recent studies suggest that T cells may play a key role in the driving and maintaining inflammation in the oesophagus. This unique study will examine the infiltration and activation of T cells in normal, oesophagitis, BO, dysplastic and OAC tissue using ex-vivo samples. A number of studies have suggested that the local immune microenvironment undergoes a radical change with the progression to adenocarcinoma, starting with an inflammatory cell-mediated like response in oesophagitis, switching to a humoral response in BO and back to an inflammatory response with the emergence of cancer. Therefore, the influence of the local microenvironment on T cell function at each disease stage will be assessed using a variety of T cell functional assays including proliferation, cytokine profiling, cytotoxicity and migration. Tissue conditioned media (TCM), generated by culturing fresh tissue biopsies representative of each disease stage, will be screened by magnetic resonance spectroscopy (NMR) to identify factors capable of regulating T cell phenotype and activation. We hypothesise that specific factors released from the oesophageal tissue as it progresses through the malignant sequence will significantly alter T cell function and ultimately accelerate disease progression. Overall this project, the first of its kind, will identify and functional validate mediators which may act as potential novel immunotherapeutic cellular or protein targets, capable of enhancing the anti-tumour immune response or prevent the progression to adenocarcinoma in these patients.
  • Funding Agency
    • Health Research Board
  • Date From
    • 1.10.12
  • Date To
    • 31.9.15
  • Title
    • Investigating the immunomodulatory properties of adipose tissue in oesophageal and colorectal cancer.
  • Summary
    • Obesity has increased markedly over the past two decades and is predicted to overtake smoking as the leading contributing factor for cancer by 2015. The aim of this research project is to study an adipose tissue bioresource from patients undergoing resective surgery for oesophageal and colorectal cancer, to investigate the mechanisms where obesity may contribute to the development and progression of these malignancies. Visceral abdominal fat has been identified as the essential fat depot for patho-genetic theories that relate obesity, metabolic syndrome and cancer. In a prospective study, subpopulations of immune cells in freshly digested, resected peripheral and omental adipose tissue will be characterised. Data will analysed comparing obese and non-obese patients, and patients with or without cancer. Immune cell population will also be assessed in the blood to determine how excess adipose tissue may regulate systemic immune responses, potentially effecting cancers at distal sites. In a retrospective study, the activation status and localisation of distinct immune cells within the tumour microenvironment will be determined by immunohistochemistry using specifically generated tissue micro-arrays. This data will be correlated with clinical parameters including BMI, visceral adiposity, metabolic syndrome status, pathological features and overall survival in order to examine the anti-tumour immune response in obese patients. The ability of adipocytes to act as antigen presenting cells and direct innate and adaptive immune responses will also be examined. This could have important implications in the role of adipose tissue in host defence, immune mediated diseases and cancer. On completion of this project it is anticipated that our knowledge of the regulatory mechanisms linking obesity, metabolic syndrome, immunomodulation and tumour growth will be greatly enhanced, which could identify novel therapeutic targets for the treatment of obesity related cancers.
  • Funding Agency
    • Health Reseach Board
  • Date From
    • 2009
  • Title
    • Investigating the role of T cells in adipose tissue and hepatic inflammation in obesity associated cancer.
  • Summary
    • Visceral obesity is considered to be a state of chronic systemic low grade inflammation, driven largely by the release of inflammatory mediators from infiltrating immune cells. Steatohepatitis, is a hepatic inflammatory consequence of visceral adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD). Recent murine studies have demonstrated that excess fat can exacerbate T cell mediated liver injury, by polarising T helper cells towards a Th-1 response. Obesity is also known to enhance lymphocyte responsiveness to hepatic chemokines, resulting in increased lymphocyte trafficking to the liver in response to inflammatory insults. However the characterisation and source of these lymphocytes in humans has not been addressed. Oesophageal adenocarcinoma (OAC) has the fastest growing incidence of all cancers, particularly in Ireland. It has the strongest association with obesity of all cancers and arises in a background of chronic inflammation making it an ideal model to study the role of T cells in adipose tissue and liver inflammation. This novel project will examine the chemoattractant properties of the human omentum and liver in attracting naive or activated T cells in OAC patients. The inflammatory profile in blood, omentum, liver and tumour will be assessed and correlated with visceral obesity. We have previously shown that large populations of activated inflammatory T cells reside within the omentum and this project aims to examine the clonality of these T cells by TCR repertoire restriction analysis and compare it to that of hepatic T cells in matched patients, where they may play a role in NAFLD. Overall this project, the first of its kind, will delineate the role of omental and hepatic T cells in maintaining chronic inflammation in obese cancer patients and potentially identify immunotherapeutic cellular or protein targets in order to control pathological inflammation and enhance anti-tumour immune responses in these patients.
  • Funding Agency
    • Health Research Board
  • Date From
    • 2011

Keywords

ADIPOCYTES; ADIPOSE TISSUE; ADIPOSE-TISSUE DISTRIBUTION; ADJUVANT RADIOTHERAPY; ADVANCED CANCER; Anticancer therapies; Autoimmunity; BARRETTS ESOPHAGUS; CACHEXIA; Cancer Biology; CANCER BIOPSIES; CANCER CHEMOTHERAPY; CANCER CLASSIFICATION; CANCER DEVELOPMENT; CANCER PATIENTS; CANCER RISK; Cancer Therapy; Cancer/Carcinogenesis; CD4+ T CELLS; CHEMO-RADIOTHERAPY; COMBINATION IMMUNOTHERAPY; Design and evaluation of novel anti-cancer therapies; Development of novel neo-adjuvant treatments for oesophageal and prostate cancer; ESOPHAGEAL CANCER; GASTRIC CANCER; Gastrointestinal cancer; HUMAN ESOPHAGEAL CANCER; HUMAN T-CELLS; Immune system; Immunoassays; Immunology, Immunotherapy; Immunotherapies for Cancer; Innate immunology; METABOLIC DISORDERS; NK CELLS; OBESITY; Radiotherapy, Biological response modifiers and chemoprevention; Regulatory T cells; Sarcopenia; Tumour immunology and immunotherapy; TUMOUR IMMUNOTHERAPY

Recognition

Awards and Honours

HRB Fellowship 2009

CROSS Research Fellowship 2008

Memberships

Treasurer and executive committee member for the Irish Society for Immunology 2014

Irish Association for Cancer Research 2011

European Association for Cancer Research 2011

European Federation of Immunological Societies 2014