Dr. James Phelan
Research Fellow, Trinity Translational Medicine Institute
Publications and Further Research Outputs
Peer-Reviewed Publications
Murphy DM, Walsh A, Stein L, Petrasca Andreea, Cox DJ, Brown K, Duffin E, Jameson G, Connolly SA, O'Connell F, O'Sullivan J, Basdeo SA, Keane J, Phelan JJ., Human Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis., International journal of molecular sciences, 25, (5), 2024, p2898
Cox DJ, Connolly SA, Ó Maoldomhnaigh C, Brugman AAI, Sandby Thomas O, Duffin E, Gogan KM, Ó Gallchobhair O, Murphy DM, O'Rourke SA, O'Connell F, Keane J, Human airway macrophages are metabolically reprogrammed by IFN-" resulting in glycolysis-dependent functional plasticity., eLife, 2024
Davern, M. and Gaughan, C. and Oâ 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
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
Murphy, D.M., Cox, D.J., Connolly, S.A., Breen, E.P., Brugman, A.A.I., Phelan, J.J., Keane, J., Basdeo, S.A., Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine, Journal of Clinical Investigation, 133, (2), 2023
Anne-Marie Baird, Martin Barr, Anne-Marie Baird, Sophia Halliday, Petra Martin, Emma H. Allott, James J. Phelan, Greg Korpanty, Linda Coate, Cathal O'Brien, Steven Gray, Jane S. Y. Sui, Brian Hayes, Sinead Cuffe, Stephen Finn, Liquid Biopsy: A Multi-Parametric Analysis of Mutation Status, Circulating Tumor Cells and Inflammatory Markers in EGFR-Mutated NSCLC, Diagnostics, 12, (10), 2022, p2360
Donlon NE, Davern M, O'Connell F, Sheppard A, Heeran A, Bhardwaj A, Butler C, Narayanasamy R, Donohoe C, Phelan JJ, Lynam-Lennon N, Dunne MR, Maher S, O'Sullivan J, Reynolds JV, Lysaght J., Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma, World Journal of Gastroenterology, 2022
Gaffney E, Murphy D, Walsh A, Connolly S, Basdeo SA, Keane J, Phelan JJ, Defining the role of neutrophils in the lung during infection: Implications for tuberculosis disease., Frontiers in immunology, 2022
Cilian Ó Maoldomhnaigh, Donal J Cox, James J Phelan, Fergal D Malone, Joseph Keane, Sharee A Basdeo, The Warburg Effect Occurs Rapidly in Stimulated Human Adult but Not Umbilical Cord Blood Derived Macrophages, Frontiers in Immunology, 2021
Phelan JJ, O'Leary S, Keane J., Tuberculosis lymph node granulomas: using transcriptomics to discover immunopathology paradigms and guide host-directed therapy, The Journal of Clinical Investigation, 2021
Abigail Keogan, Thi Nguyet Que Nguyen, James J. Phelan, Niamh Lynam-Lennon, C. Muldoon, A. A. Maguire, D. O'Toole, John V. Reynolds, Jacintha O'Sullivan, Aidan D Meade., Chemical imaging and machine learning for sub-classification of oesophageal tissue histology, Translational Biophotonics, 2021
Christina Cahill, Fiona O'Connell, Karl M Gogan, Donal J Cox, Sharee A Basdeo, Jacintha O'Sullivan, Stephen V Gordon , Joseph Keane, James J Phelan, The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG, International Journal of Molecular Sciences, 2021
Christina Cahill, Dónal J. Cox, Fiona O'Connell, Sharee A. Basdeo, Karl M. Gogan, Cilian Ó'Maoldomhnaigh, Jacintha O'Sullivan, Joseph Keane and James J. Phelan., The Effect of Tuberculosis Antimicrobials on the Immunometabolic Profiles of Primary Human Macrophages Stimulated with Mycobacterium tuberculosis, International Journal of Molecular Sciences, 2021
James J. Phelan and Frederick J. Sheedy., Phagocyte metabolism: neutrophils have their cake but don't eat it., Trends in Immunology, 2021
Noel E Donlon, Maria Davern, Andrew Sheppard, Robert Power, Fiona O'Connell, Aisling B Heeran, Ross King, Conall Hayes, Anshul Bhardwaj, James J Phelan, Margaret R Dunne, Narayanasamy Ravi, Claire L Donohoe, Jacintha O'Sullivan, John V Reynolds, Joanne Lysaght., The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling, Cancers, 2021
Cilian Ó Maoldomhnaigh, Donal J Cox, James Joseph Phelan, Karl M. Gogan, Kate McQuaid, Amy Martina Coleman, Sharee Ann Basdeo and Joseph Keane., Lactate alters metabolism in human macrophages and improves their ability to kill Mycobacterium tuberculosis, Frontiers in Immunology, 2021
Cox, D.J., Coleman, A.M., Gogan, K.M., Phelan, J.J., Maoldomhnaigh, C., Dunne, P.J., Basdeo, S.A. and Keane, J., Inhibiting histone deacetylases in human macrophages promotes glycolysis, IL-1β and T helper cell responses to Mycobacterium tuberculosis, Frontiers in Immunology, 2020
G. Barber, A. Anand, K. Oficjalska, J.J. Phelan, A. B. Heeran, E. Flis, N. E. Clarke, J. A. Watson, J. Strangmann, B. Flood, H. O'Neill, D. O'Toole, F. MacCarthy, N. Ravi, J. V. Reynolds, E.W. Kay, M. Quante, J. O'Sullivan, E.M. Creagh., Characterizing caspase-1 involvement during esophageal disease progression. , Cancer Immunology Immunotherapy, 69, (12), 2020, p2635 - 2649
Cahill, C.*, Phelan, J.J.* and Keane, J, Understanding and exploiting the effect of tuberculosis antimicrobials on host mitochondrial function and bioenergetics, Frontiers in Cellular and Infection Microbiology, 2020
Phelan J.J., McQuaid, K., Kenny C., Gogan K.M., Cox D.J., Basdeo S.A., O'Leary S., Tazoll S.C., Ó Maoldomhnaigh C., O'Sullivan M.P., O'Neill LA, O'Sullivan M.J. & Keane J., Desferrioxamine supports metabolic function in primary human macrophages infected with Mycobacterium tuberculosis, Frontiers in Immunology, 2020
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
Dunne M.R.*, Phelan J.J.*, Michielsen A.J., Maguire A.A., Dunne C., Martin P., Noonan S., Tosetto M., Geraghty R., Fennelly D., Sheahan K., Ryan E.J., O'Sullivan J. (joint 1st author *), Characterising the prognostic potential of HLA-DR during colorectal cancer development., Cancer Immunology Immunotherapy, 2020
Petrasca Andreea, Phelan James .J., Ansboro Sharon, Veale Douglas J., Fearon Ursula, Fletcher Jean M., Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in rheumatoid arthritis., Rheumatology, 2020
Naoimh J. O'Farrell, James J. Phelan, Ronan Feighery, Brendan Doyle, Sarah L. Picardo, Ravi Narayanasamy, Dermot O'Toole, John V. Reynolds, Jacintha O'Sullivan, Differential expression profiles of oxidative stress levels, 8-oxo-dG and 4-HNE, in Barrett's esophagus compared to esophageal adenocarcinoma, International Journal of Molecular Sciences, 2019
Melo, Ashanty M., O'Brien, Aisling M., Phelan, James J., Kennedy, Susan A., Wood, Nicole A. W., Veerapen, Natacha, Besra, Gurdyal S., Clarke, Niamh E., Foley, Emma K., Ravi, Akshaya, MacCarthy, Finbar, O'Toole, Dermot, Ravi, Narayamasami, Reynolds, John V., Conroy, Melissa J., Hogan, Andrew E., O'Sullivan, Jacintha, Dunne, Margaret R., Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma, Frontiers in Immunology, 10, 2019
Francesco Caiazza, Katarzyna Oficjalska, Miriam Tosetto, James J. Phelan, SinéadNoonan, Petra Martin, Kate Killick, Laura Breen, Fiona O'Neill, Blathnaid Nolan, Simon Furney, Robert Power, David Fennelly, Charles S. Craik, Jacintha O'Sullivan, Kieran Sheahan, Glen A. Doherty, Elizabeth J. Ryan, KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment, The American Journal of Pathology, 2019
Phelan JJ, Basdeo SA, Tazoll SC, McGivern S, Saborido JR and Keane J, Modulating Iron for Metabolic Support of TB Host Defense, Frontiers in Immunology, 2018
James J. Phelan, Finbar MacCarthy, Dermot O'Toole, Narayanasamy Ravi, John V. Reynolds and Jacintha O'Sullivan, The Mitochondrial Genes BAK1, FIS1 and SFN are Linked with Alterations in Mitochondrial Membrane Potential in Barrett's Esophagus, International Journal of Molecular Sciences, 19, (11), 2018
Widdowson, W.M., McGowan, A., Phelan, J.J., Boran, G., Reynolds, J.V., and Gibney, J., Vascular disease is associated with the expression of genes for intestinal cholesterol transport and metabolism, Journal of Clinical Endocrinology & Metabolism, 102, (1), 2017, p326-335
Dowling CM, Hayes SL, Phelan J.J., Cathcart MC, Finn SP, Mehigan B, McCormick P, Coffey JC, O'Sullivan J and Kiely PA, Expression of protein kinase C gamma promotes cell migration in colon cancer, Oncotarget, 8, (42), 2017, p72096-72107
Dowling C, Phelan J, Cathcart M, Mehigan B, McCormick P, Dalton T, Coffey C, Newton A, O'Sullivan J and Kiely P., Protein Kinase C Beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival, Oncotarget, 7, 2016, p20919-20933
Biniecka, M., Canavan, M., McGarry, T., Gao, W., McCormick, J., Cregan, S., Gallagher, L., Smith T., Phelan, J.J., Ryan, J., O'Sullivan, J., Nq, C.T., Veale, D.J. and Fearon, U., 'Dysregulated bioenergetics: a key regulator of joint inflammation'., Annals of Rheumatic diseases., 75, (12), 2016, p2192-2200
Phelan, J.J., Feighery, R., Eldin, O.S., MacCarthy, F., O'Toole, D., Reynolds, J.V. and O'Sulllivan, J., Examining the connectivity between different cellular processes in the Barrett tissue microenvironment: energy metabolism, hypoxia, inflammation, p53 and obesity., Cancer Letters, 371, (2), 2016, p334 - 346
O'Farrell N.J, Feighery R, Picardo S.L, Lynam-Lennon N, Biniecka M, McGarrigle S.A, Phelan J.J, MacCarthy F, O'Toole D, Fox E.J, Ravi N, Reynolds J.V, O'Sullivan J, Changes in mitochondrial stability during the progression of the Barrett's esophagus disease sequence, BMC Cancer, 16, (1), 2016, p497-
Phelan JJ, O'Hanlon C, Reynolds JV, O'Sullivan J., 'The role of energy metabolism in driving disease progression in inflammatory, hypoxic and angiogenic microenvironments'., Gastro Open Journal, 1, (2), 2015, p44-58
Lynam-Lennon, N., Maher, S.G., Maguire, A., (...), Reynolds, J.V., O'Sullivan, J., Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma, PLoS ONE , 9, (6), 2014, pe100738-
Phelan JJ, MacCarthy F, Feighery R, O'Farrell NJ, Lynam-Lennon N, Doyle B, O'Toole D, Ravi N, Reynolds JV, O'Sullivan J., Differential expression of mitochondrial energy metabolism profiles across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett's oesophagus'., Cancer Letters, 354, (1), 2014, p122 - 131
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
Research Expertise
Projects
- Title
- Programme Manager for the AllCaN Oesophageal Programme
- Summary
- The All-Ireland Cancer Network (AllCaN) Programme Grant is a Breakthrough Cancer Research funding programme that started in 2021. The Programme Grant is designed to fund networks of the best scientists/researchers at institutions across the island of Ireland, to develop new and innovative approaches to improving cancer outcomes. Researchers collaborate across disciplines, institutions, and as appropriate across the four pillars of prevention, detection, treatment and survivorship. The successful researchers work together on a common goal, pooling their knowledge and resources to work together to eliminate barriers and to hasten the progression needed to improve patient outcomes. The AllCaN Oesophageal programme represents a new, focused effort to implement advances in Oesophageal Cancer research as rapidly as possible through the creation of a collaborative, translational cancer research network. The most talented and promising researchers across Irish institutions have been assembled into an All-Ireland Research Network forming an optimal configuration of expertise needed to solve key problems in Oesophageal Cancer research and positively impact patients in the near future.
- Funding Agency
- Breakthrough Cancer Research
- Date From
- July 2023
- Date To
- Present
- Title
- Defining the role of macrophage-mediated recruitment of neutrophils in the fight against Mycobacterium tuberculosis infection
- Summary
- Tuberculosis (TB) remains a global scourge causing approximately 1.5 million deaths annually. The increasing prevalence of drug-resistant TB demonstrates that current treatments are inadequate and there is an urgent need for better therapies. One research strategy in TB is focused on finding new treatments which can be used alongside existing TB drugs to help a patient's own immune cells fight TB. The chief immune cells of the lung, alveolar macrophages, are the first line of defence against TB infection. Other immune cells, including neutrophils, can respond early and can kill TB. In fact, mycobacterial infections are more common in patients with defects in neutrophil function. However, Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, can manipulate immune responses to allow it to live and replicate inside macrophages and neutrophils. Therefore, finding ways to modulate the macrophageneutrophil axis during Mtb infection could have great clinical benefit. Reducing iron levels in immune cells can improve their immune function. Mtb also requires iron for its survival, so lowering iron levels has been suggested as a possible adjunctive TB therapy. My research shows that reducing iron levels, using a drug that treats patients with iron overload called desferrioxamine (DFX), boosts the ability of human alveolar macrophages to fight Mtb. Preliminary evidence indicates that DFX may enhance the ability of macrophages to recruit neutrophils to the lung, to help kill Mtb. This proposal examines how DFX can help macrophages recruit neutrophils and will study the immunological features characterising these recruited neutrophils, allowing us to improve their immune responses to enhance their ability to kill Mtb. The goal of this research is to provide proof-of-concept data for the use of DFX as a therapy to treat Mtb infection while also gaining valuable insight into how macrophages and neutrophils co-operate to mediate immunity against Mtb.
- Funding Agency
- Irish Research Council
- Date From
- 1st October 2020
- Date To
- 30th September 2022
- Title
- Evaluating the immunometabolic potential of desferrioxamine to augment antibiotic treatment against Mycobacterium tuberculosis
- Summary
- Tuberculosis (TB) remains a global scourge causing more than one million deaths annually. TB therapy is characterised by a long duration of treatment and the administration of a number of antibiotic drugs to overcome drug resistance. The increasing prevalence of drug-resistant TB demonstrates that current treatments are inadequate and there is an urgent need for novel therapies. Research is now focused on the development of host-directed therapies (HDTs) which can be used in combination with existing antimicrobials, with a special focus on promoting host defense, particularly cellular metabolism. Immunometabolic reprogramming is integral to TB host defense and fundamental to eradicating TB infection. Moreover, TB pathophysiology is interconnected with iron metabolism. Iron is crucial for the survival of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB disease. Iron chelation has therefore been suggested as a HDT. In addition to its direct effects on iron availability, it is hypothesised that iron chelators can also enhance immunometabolism through the stabilisation of HIF1α. We propose to evaluate the immunometabolic potential of anti-TB agents in combination with the iron chelator, desferrioxamine (DFX), to examine if such anti-TB/DFX combinatorial agents can augment antibiotic efficacy in human alveolar macrophages infected with clinical isolates of drug-resistant Mtb.
- Funding Agency
- Science Foundation Ireland
- Date From
- 1st April 2019
- Date To
- 31st March 2020
Recognition
Awards and Honours
SFI/EI Technology Innovation Development Award (TIDA) (€127,349.00)
Irish Research Council Government of Ireland Postdoctoral Fellowship (€91,970.00)
British Society for Immunology - Travel Award (£1000)
Stemcell Technologies 2021 Immunology Travel Grant ($500)
British Society for Immunology Travel Award (£250)
Best Oral Presentation at the Irish Area Section of the Biochemical Society (IASBS) Conference
Gold Trinity Access Programmes Ambassador Certificate (x2) from the Trinity Access Programme in Trinity College Dublin