Dr. James Phelan

• 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 - 760Journal Article, 2014, DOI , TARA - Full Text
• Phelan JJ, Feighery R, Eldin OS, Meachair SÓ, Cannon A, Byrne R, MacCarthy F, O'Toole D, Reynolds JV, O'Sullivan J, Examining the connectivity between different cellular processes in the Barrett tissue microenvironment., Cancer letters, 371, (2), 2016, p334-46Journal Article, 2016, DOI
• 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, p20919-20933Journal Article, 2016, DOI , TARA - Full Text
• Biniecka M, Canavan M, McGarry T, Gao W, McCormick J, Cregan S, Gallagher L, Smith T, Phelan JJ, Ryan J, O'Sullivan J, Ng CT, Veale DJ, Fearon U, Dysregulated bioenergetics: a key regulator of joint inflammation., 75, (12), 2016, p2192-2200Journal Article, 2016, DOI
• 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-Journal Article, 2016, DOI , URL , TARA - Full Text
• 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, p72096-72107Journal Article, 2017, DOI , URL
• 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, p326-335Journal Article, 2017, DOI , URL , TARA - Full Text
• O'Farrell NJ, Feighery R, Picardo SL, Lynam-Lennon, N., Biniecka, M., McGarrigle, S., Phelan J.J., MacCarthy, F., O'Toole, D., Fox EJ, Ravi, N., Reynolds JV, O'Sullivan JN., 'Changes in mitochondrial stability during the progression of the Barrett's esophagus sequence'., BMC Cancer, 2016Journal Article, 2016, DOI , URL , TARA - Full Text
• 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, p2192-2200Journal Article, 2016, DOI , URL , TARA - Full Text
• Dowling, C.M., Phelan, J.J., Callender, J.A., Cathcart, M.C., Mehigan, B., McCormick, P., Dalton, T., Coffey, J.C. Newton A.C., O'Sullivan, J. and Kiely P.A., 'Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival'., Oncotarget, 7, (15), 2016, p20919 - 20933Journal Article, 2016, DOI , URL , TARA - Full Text
• 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 - 346Journal Article, 2016, DOI , URL , TARA - Full Text
• 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, p44-58Journal Article, 2015, DOI , URL , TARA - Full Text
• 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 - 131Journal Article, 2014, DOI , URL , TARA - Full Text
• Lynam-Lennon N, Maher SG, Maguire A, Phelan J, Muldoon C, Reynolds JV, O'Sullivan J., 'Altered Mitochondrial Function and Energy Metabolism Is Associated with a Radioresistant Phenotype in Oesophageal Adenocarcinoma'., PLOS ONE, 9, (6), 2014Journal Article, 2014, DOI , URL , TARA - Full Text
• 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 review of gastroenterology & hepatology., Expert review of gastroenterology & hepatology, 8, (7), 2014, p749 - 760Journal Article, 2014, DOI , URL
• 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, 2018Journal Article, 2018, DOI , URL , TARA - Full Text
• 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), 2018Journal Article, 2018, DOI , URL , TARA - Full Text
• 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, 2019Journal Article, 2019, DOI , TARA - Full Text
• 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, 2019Journal Article, 2019, DOI , URL , TARA - Full Text
• 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, 2019Journal Article, 2019, DOI , URL , TARA - Full Text
• Petrasca A, Phelan J.J., Ansboro S, Veale D.J., Fearon U., Fletcher J.M., Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in rheumatoid arthritis., Rheumatology, 2020Journal Article, 2020, DOI , URL
• 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, 2020Journal Article, 2020, DOI , URL , TARA - Full Text
• 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, 2020Journal Article, 2020, DOI , URL , TARA - Full Text
• Gillian Barber, Akanksha Anand, Katarzyna Oficjalska, James J Phelan, Aisling B Heeran, Ewelina Flis, Niamh E Clarke, Jenny A Watson, Julia Strangmann, Brian Flood, Hazel O'Neill, Dermot O'Toole, Finbar MacCarthy, Narayanasamy Ravi, John V Reynolds, Elaine W Kay, Michael Quante, Jacintha O'Sullivan, Emma M Creagh, Characterizing caspase‑1 involvement during esophageal disease progressio, Cancer Immunology, Immunotherapy, 2020Journal Article, 2020, DOI , URL
• 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, 2020Journal Article, 2020, DOI , URL , TARA - Full Text
• 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, 2020Journal Article, 2020, DOI , URL , TARA - Full Text
• 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, p3356Journal Article, 2020, TARA - Full Text
• Phelan, J.J. and Maccarthy, F. and O†toole, D. and Ravi, N. and Reynolds, J.V. and O†sullivan, J., 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), 2018Journal Article, 2018, DOI , URL
• 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, 2021Journal Article, 2021, DOI , URL , TARA - Full Text
• 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, 2021Journal Article, 2021, DOI , URL
• 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, 2021Journal Article, 2021, DOI , URL
• 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, 2021Journal Article, 2021, DOI , URL
• 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, 2021Journal Article, 2021
• James J. Phelan and Frederick J. Sheedy., Phagocyte metabolism: neutrophils have their cake but don't eat it., Trends in Immunology, 2021Journal Article, 2021, DOI , URL
• 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, 2021Journal Article, 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, 2021Journal Article, 2021, DOI , URL , TARA - Full Text
• Noel E Donlon, Maria Davern, Fiona O'Connell, Andrew Sheppard, Aisling Heeran, Anshul Bhardwaj, Christine Butler, Ravi Narayanasamy, Claire Donohoe, James J Phelan, Niamh Lynam-Lennon, Margaret R Dunne, Stephen Maher, Jacintha O'Sullivan, John V Reynolds and Joanne Lysaght, The impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma, World Journal of Gastroenterology, 2022Journal Article, 2022
• Donlon, N.E. and Davern, M. and Sheppard, A. and Power, R. and O†connell, F. and Heeran, A.B. and King, R. and Hayes, C. and Bhardwaj, A. and Phelan, J.J. and Dunne, M.R. and Ravi, N. and Donohoe, C.L. and O†sullivan, J. and Reynolds, J.V. and Lysaght, J., The prognostic value of the lymph node in oesophageal adenocarcinoma; incorporating clinicopathological and immunological profiling, Cancers, 13, (16), 2021Journal Article, 2021, DOI , URL
• Cahill, C. and Cox, D.J. and O†connell, F. and Basdeo, S.A. and Gogan, K.M. and Ã"†maoldomhnaigh, C. and O†sullivan, J. and Keane, J. and Phelan, J.J., The effect of tuberculosis antimicrobials on the immunometabolic profiles of primary human macrophages stimulated with mycobacterium tuberculosis, International Journal of Molecular Sciences, 22, (22), 2021Journal Article, 2021, DOI , URL
• Cahill, C. and O†connell, F. and Gogan, K.M. and Cox, D.J. and Basdeo, S.A. and O†sullivan, J. and Gordon, S.V. and Keane, J. and Phelan, J.J., The iron chelator desferrioxamine increases the efficacy of bedaquiline in primary human macrophages infected with bcg, International Journal of Molecular Sciences, 22, (6), 2021, p1-15Journal Article, 2021, DOI , URL
• 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), 2023Journal Article, 2023, DOI
• Murphy DM, Walsh A, Stein L, Petrasca A, 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, p2898Journal Article, 2024, DOI
• 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-Journal Article, 2014, DOI , TARA - Full Text

• 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

Clinical Medicine, Other health sciences, Other clinical medicine, Genetics, Other basic medicine and life sciences, Immunology, Cancer,

• SFI/EI Technology Innovation Development Award (TIDA) (€127,349.00) 2019
• Irish Research Council Government of Ireland Postdoctoral Fellowship (€91,970.00) 2020-2022
• British Society for Immunology - Travel Award (£1000) November 2018

• I have presented six posters at international conferences including the BSI (2017, Brighton), the 7th & 9th National Barrett's Symposium (2013 &2015, London), Keystone's Tumor Metabolism Conference (2014, Canada), at the European Association of Cancer Research (EACR23) (2014, Munich) and at Abcam's Cancer and Metabolism Conference (2013, Amsterdam).