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Professor Joanne Lysaght

Professor In (Surgery)
TRINITY CENTRE, S J H
      
Profile Photo

Professor Joanne Lysaght

Professor In (Surgery)
TRINITY CENTRE, S J H

 jlysaght@tcd.ie

 3531896 4259


Prof. 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. Prof. 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 she Lysaght was appointed Ussher Assistant Professor in Molecular Oncology, in 2015 Assistant Professor, in 2017 Associate Professor and Professor in Cancer Immunology and Immunotherapy in 2023, where she continues her research in cancer immunology and immunotherapy. Prof. 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 but also gastric and pancreatic 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 and pancreatic cysts, 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. Prof. Lysaght's group also investigates the role of adaptive immunity and obesity in the debilitating cancer-associated wasting disease cachexia and sarcopenia.
  Anticancer therapies   BARRETTS ESOPHAGUS   CACHEXIA   Cancer Biology   CANCER CHEMOTHERAPY   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   ESOPHAGEAL CANCER   GASTRIC CANCER   Gastrointestinal cancer   HUMAN ESOPHAGEAL CANCER   HUMAN T-CELLS   Immune system   Immunology, Immunotherapy   Immunotherapies for Cancer   NK CELLS   OBESITY   Radiotherapy, Biological response modifiers and chemoprevention   Regulatory T cells   Sarcopenia   Tumour immunology and immunotherapy   TUMOUR IMMUNOTHERAPY
Project Title
 Investigating the immunomodulatory properties of adipose tissue in oesophageal and colorectal cancer.
From
2009
To
2012
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
Programme
Post-Doctoral Fellowship
Project Title
 Investigating the role of T cells in adipose tissue and hepatic inflammation in obesity associated cancer.
From
2011
To
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
Project Type
Program
Project Title
 Evaluating the role of T cells in the progression of Barrett's Oesophagus to Oesophageal Adenocarcinoma: identification of novel immunotherpeutic targets
From
1.10.12
To
31.9.15
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
Programme
HRA
Person Months
36
Project Title
 Immunophenotyping of pancreatic cystic lesions
From
2021
To
2025
Summary
Funding Agency
Trinity College Dublin
Programme
Provost's PhD Award
Project Type
PhD
Project Title
 Elucidating the role of the Fractalkine pathway in NK cell migration to the adipose tissue in obese cancer patients
From
To
Summary
Funding Agency
Breakthrough Cancer Research
Programme
BCR PhD Scholarship
Project Type
PhD

Page 1 of 3
Details Date
Irish representative (As President of the Irish Society for Immunology) at the second European Federation of Immunological societies (EFIS) Strategic Planning Meeting in Italy, November 2022. EFIS governs a number of taskforces and research groups, which help generate policies for European Governments on immunological issues such as vaccinations and Covid. November
Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
Irish Basic Basic Basic
Details Date From Date To
President of the Irish Society for Immunology 2022
Senior Council Member of the Irish Association for Cancer Research 2017 2022
European Association for Cancer Research 2011
European Federation of Immunological Societies 2014
International Union of Immunological Societies 2015
Cancer Trials Ireland 2012
Society for Immunotherapy of Cancer (SITC) 2020
O'Brien, R.M. and Meltzer, S. and Buckley, C.E. and Heeran, A.B. and Nugent, T.S. and Donlon, N.E. and Reynolds, J.V. and Ree, A.H. and Redalen, K.R. and Hafeez, A. and O'Ríordáin, D.S. and Hannon, R.A. and Neary, P. and Kalbassi, R. and Mehigan, B.J. and McCormick, P.H. and Dunne, C. and Kelly, M.E. and Larkin, J.O. and O'Sullivan, J. and Lysaght, J. and Lynam-Lennon, N., Complement is increased in treatment resistant rectal cancer and modulates radioresistance, Cancer Letters, 604, (217253), 2024, Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Lysaght J, Conroy MJ., The multifactorial effect of obesity on the effectiveness and outcomes of cancer therapies., Nature reviews. Endocrinology, 20, (12), 2024, p701-714 , Journal Article, PUBLISHED  DOI
Connor AE, Lyons PM, Kilgallon AM, Simpson JC, Perry AS, Lysaght J., Examining the evidence for immune checkpoint therapy in high-grade serous ovarian cancer., Heliyon, 10, (20), 2024, pe38888 , Journal Article, PUBLISHED  DOI
Davern, M. and Bracken-Clarke, D. and Donlon, N.E. and Sheppard, A.D. and Connell, F.O. and Heeran, A.B. and Majcher, K. and Conroy, M.J. and Mylod, E. and Butler, C. and Donohoe, C. and Donnell, D.O. and Lowery, M. and Bhardwaj, A. and Ravi, N. and Melo, A.A. and Sullivan, J.O. and Reynolds, J.V. and Lysaght, J., Visceral adipose tissue secretome from early and late-stage oesophageal cancer patients differentially affects effector and regulatory T cells, Journal of Cancer Research and Clinical Oncology, 2023, Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Davern M, Donlon NE, O'Connell F, Gaughan C, O'Donovan C, Habash M, Sheppard AD, MacLean M, Dunne MR, Moore J, Temperley H, Conroy MJ, Butler C, Bhardwaj A, Ravi N, Donohoe CL, Reynolds JV, Lysaght J., Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients, Cancer Immunology Immunotherapy, 2023, Journal Article, PUBLISHED  TARA - Full Text  DOI
Moran B, Davern M, Reynolds JV, Donlon NE, Lysaght J., The impact of histone deacetylase inhibitors on immune cells and implications for cancer therapy, Cancer Letters, 2023, Journal Article, PUBLISHED  DOI
Moran J, Mylod E, Kane LE, Marion C, Keenan E, Mekhaeil M, Lysaght J, Dev KK, O'Sullivan J, Conroy MJ., Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses, Pharmaceutics, 2023, Journal Article, PUBLISHED  TARA - Full Text  DOI
Davern, M. and Gaughan, C. and O†Connell, F. and Moran, B. and Mylod, E. and Sheppard, A.D. and Ramjit, S. and Yun-Tong Kung, J. and Phelan, J.J. and Davey, M.G. and Ryan, E.J. and Butler, C. and Quinn, L. and Howard, C. and Tone, E. and Phoenix, E. and Butt, W.T. and Lynam-Lennon, N. and Maher, S.G. and Ravi, N. and Donohoe, C.L. and Reynolds, J.V. and Lysaght, J. and Donlon, N.E., PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma, Frontiers in Immunology, 14, (1150754), 2023, Notes: [cited By 1], Journal Article, PUBLISHED  DOI
Donlon, N.E. and Davern, M. and Sheppard, A. and O'Connell, F. and Moran, B. and Nugent, T.S. and Heeran, A. and Phelan, J.J. and Bhardwaj, A. and Butler, C. and Ravi, N. and Donohoe, C.L. and Lynam-Lennon, N. and Maher, S. and Reynolds, J.V. and Lysaght, J., Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer, World Journal of Gastrointestinal Oncology, 15, (8), 2023, p1349-1365 , Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Noel Donlon, Maria Davern, Andrew Sheppard, Claire Donohoe, John Reynolds, Joanne Lysaght, Novel methods to enhance anti-tumour immunity in oesophageal adenocarcinoma; hypofractionated radiotherapy may be superior to CROSS regimen chemo-radiation, British Journal of Surgery, Association of Surgeons of Great Britain and Ireland, Annual Congress, Liverpool, 3-5th May 2022, 109, (Supplement_5), 2022, Conference Paper, PUBLISHED
  

Page 1 of 11
Cliona M Lorton, John V Reynolds, Joanne Lysaght, ASO Author Reflections: Can CRP and CRP-Based Scores Predict Survival in Operable Adenocarcinomas of the Esophagus and Esophago-Gastric Junction?, Annals of Surgical Oncology, 2021, Journal Article, PUBLISHED
Cliona M Lorton, Larissa Higgins, Niamh O'Donoghue, Claire Donohoe, Jim O'Connell, David Mockler, John V Reynolds, Declan Walsh, Joanne Lysaght, ASO Visual Abstract: C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-analysis, Annals of Surgical Oncology, 2021, Journal Article, PUBLISHED

  


Award Date
Award for Excellence in Supervision of Research Students-School of Medicine Main Award June 2022
HRB Post-Doctoral Fellowship 2009
CROSS Research Fellowship 2008
My translational research group focuses on the central theme of cancer immunology and immunotherapy, an area that continues to revolutionise treatment for cancer patients worldwide. Cancer immunotherapy has offered cures and extended the lives of countless cancer patients, where no options existed before, but this field is still in its relative infancy. The majority of research in my group is focused on dismal upper gastrointestinal cancers, particularly obesity-associated oesophageal cancer but also gastric, pancreatic and ovarian cancer. A key research direction of my research is understanding how the physical features of the tumour microenvironment, immunometabolism and the cancer treatment itself can affect immune cells, namely T cells, and their functions in cancer patients. This work has been reported in 85 peer-reviewed publications in international journals. Understanding the hurdles faced by T cells in cancer patients will lead to identification of novel and more effective treatment combinations, including immune checkpoint inhibitors with chemotherapy and radiotherapy. It will help identify biomarkers of response and treatment resistance which can be used in the clinical management of these patients. Research into the regulation and chemotaxis (movement) of lymphocytes to reduce pathological inflammation and enhance anti-tumour immunity is another important research theme within my group. My group utilize a range of in vitro and ex vivo molecular and cellular analytical techniques and I have established productive multi-disciplinary collaborations with academic, clinical and industrial partners, both nationally and internationally. To conduct my research, I have received funding from Science Foundation Ireland, Health Research Board, the Irish Cancer Society, Breakthrough Cancer Research and the Irish Research Council.