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Dr. James Phelan

Research Fellow (Trinity Translational Medicine Institute)
      
Profile Photo

Dr. James Phelan

Research Fellow (Trinity Translational Medicine Institute)

 phelanj3@tcd.ie

 


  Angiogenesis, oncology, cardiovascular biology, inflammation   ANTI-CANCER DRUG DESIGN   ANTICANCER DRUGS   BACTERIAL INFECTION   BARRETTS ESOPHAGUS   BARRETTS-ESOPHAGUS   Biochemistry, metabolism   BOVINE TUBERCULOSIS   CANCER   CANCER CELL-LINE   CANCER PATIENTS   CANCER RISK   CANCER SUSCEPTIBILITY GENE   CANCER TREATMENT   CANCER-CELLS   CANCER-PATIENTS   CANCERS   Carbohydrates, Other Macromolecules Metabolism   CHEST INFECTIONS   CHRONIC INFLAMMATION   COINFECTION   Colorectal Cancer   Cytology and Cancerology   Development of novel anti-cancer drugs   Development of novel neo-adjuvant treatments for oesophageal and prostate cancer   DYSPLASIA   ELECTRON-TRANSPORT   ENERGY-METABOLISM   ESOPHAGEAL CANCER   FATTY ACID   FATTY ACID OXIDATION   FATTY-ACID SYNTHESIS   GASTROESOPHAGEAL REFLUX   GASTROESOPHAGEAL REFLUX DISEASE   GASTRO-OESOPHAGEAL REFLUX   Gastro-oesophageal reflux disease   GLUCOSE METABOLISM   GLUCOSE-METABOLISM   GLUTAMATE   GLUTAMINE   GLUTAMINE METABOLISM   GLUTAMINE SYNTHETASE   Glycolysis   HELICOBACTER PYLORI INFECTION   IMMUNOLOGY   Immunology, Immunotherapy   Immunometabolism   INFECTION   Inflammation   INFLAMMATION-INDUCED EXPRESSION   Innate immunology   INTESTINAL INFECTIONS   INTESTINAL INFLAMMATION   LACTATE AND ACETATE METABOLISM   L-GLUTAMINE   Lipid metabolism   LIPID-METABOLISM   L-TRYPTOPHAN   LUNG INFECTION   metabolism   Metabolism and metabolic diseases   Metabolism, Amino Acid   Metabolism, Lipid   Metabolism, Mineral   Metabolism, Nucleotide   Metabolism, Protein   Mitochondria   MITOCHONDRIAL   mitochondrial aspartate/glutamate   MITOCHONDRIAL COMPLEX I   MITOCHONDRIAL COMPLEX-I   MITOCHONDRIAL DNA   MITOCHONDRIAL DNA (MTDNA)   Mitochondrial fission & fusion mechanisms   Mitochondrial function   MITOCHONDRIAL INNER MEMBRANE   MITOCHONDRIAL MATRIX   MITOCHONDRIAL OUTER MEMBRANE   MITOCHONDRIAL OUTER-MEMBRANE   MITOCHONDRIAL RESPIRATION   MITOCHONDRIAL RESPIRATORY COMPLEX I   MITOCHONDRIAL RESPIRATORY-CHAIN   MITOCHONDRIAL UNCOUPLING PROTEIN   MITOCHONDRIAL-DNA   MITOCHONDRIAL-MEMBRANE POTENTIAL   Molecular Immunology   MYCOBACTERIUM INFECTION   Mycobacterium tuberculosis   MYCOBACTERIUM-TUBERCULOSIS   Oesophageal Cancer   OXIDATIVE INJURY   OXIDATIVE PHOSPHORYLATION   OXIDATIVE POTENTIAL   OXIDATIVE STRESS   OXIDATIVE-METABOLISM   OXIDATIVE-PHOSPHORYLATION   PENTOSE-PHOSPHATE PATHWAY   PREVENTION OF TUBERCULOSIS   PULMONARY TUBERCULOSIS   RESISTANT TUBERCULOSIS   RESPIRATORY INFECTION   TB immunology   TRIACYLGLYCEROL METABOLISM   TRYPTOPHAN   Tuberculosis   TUBERCULOSIS TRANSMISSION   Tumor Immunology   Tumour Biology/ Immunology   Tumour immunology and immunotherapy
Project Title
 Programme Manager for the AllCaN Oesophageal Programme
From
July 2023
To
Present
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
Programme
AllCaN Oesophageal
Project Type
Consortium
Person Months
48
Project Title
 Defining the role of macrophage-mediated recruitment of neutrophils in the fight against Mycobacterium tuberculosis infection
From
1st October 2020
To
30th September 2022
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
Programme
Postdoctoral Fellowship (Government of Ireland)
Project Type
Research (Proof of Principal)
Person Months
24
Project Title
 Evaluating the immunometabolic potential of desferrioxamine to augment antibiotic treatment against Mycobacterium tuberculosis
From
1st April 2019
To
31st March 2020
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
Programme
Technology Innovation Development Award
Project Type
Research (Proof of Principal)
Person Months
12

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 , Journal Article, PUBLISHED  DOI
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, Journal Article, PUBLISHED  DOI
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, Journal Article, PUBLISHED  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
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 , Journal Article, PUBLISHED  DOI
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, Journal Article, PUBLISHED  DOI
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, Journal Article, PUBLISHED
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, Journal Article, PUBLISHED  TARA - Full Text  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, 2021, Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
  

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Award Date
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
Stemcell Technologies 2021 Immunology Travel Grant ($500) December 2021
British Society for Immunology Travel Award (£250) December 2021
Best Oral Presentation at the Irish Area Section of the Biochemical Society (IASBS) Conference November 2012
Gold Trinity Access Programmes Ambassador Certificate (x2) from the Trinity Access Programme in Trinity College Dublin 2009 & 2010