Dr. Sharee Basdeo

• Basdeo, S.A., Moran, B., Cluxton, D., (...), Fearon, U., Fletcher, J.M., Polyfunctional, pathogenic CD161⁺ Th17 lineage cells are resistant to regulatory T cell-mediated suppression in the context of autoimmunity, Journal of Immunology, 195, (2), 2015, p528-540Journal Article, 2015, DOI
• Basdeo SA, Moran B, Cluxton D, Canavan M, McCormick J, Connolly M, Orr C, Mills KH, Veale DJ, Fearon U, Fletcher JM, Polyfunctional, Pathogenic CD161+ Th17 Lineage Cells Are Resistant to Regulatory T Cell-Mediated Suppression in the Context of Autoimmunity., Journal of immunology (Baltimore, Md. : 1950), 195, (2), 2015, p528-40Journal Article, 2015, DOI
• Basdeo S.A, Campbell N.K, Sullivan L.M, Flood B, Creagh E.M, Mantle T.J, Fletcher J.M, Dunne A, Suppression of human alloreactive T cells by linear tetrapyrroles; relevance for transplantation, Translational Research, 178, 2016, p81-94.e2Journal Article, 2016, DOI , URL , TARA - Full Text
• Sharee A. Basdeo, Deborah Cluxton, Jamal Sulaimani, Barry Moran, Mary Canavan, Carl Orr, Douglas J. Veale, Ursula Fearon and Jean M. Fletcher, Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells, Journal of Immunology, 2017Journal Article, 2017, DOI
• Basdeo SA, Kelly S, O'Connell K, Tubridy N, McGuigan C, Fletcher JM., Increased expression of Tbet in CD4(+) T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS., SpringerPlus, 2016Journal Article, 2016, DOI
• Farver-Vestergaard, Ingeborg and O{\textquoteright, Mindfulness-based cognitive therapy in COPD: a cluster randomised controlled~trial, European Respiratory Journal, 51, (2), 2018Journal Article, 2018, DOI , URL
• O'Connell K, Sulaimani J, Basdeo SA, Kinsella K, Jordan S, Kenny O, Kelly SB, Murphy D, Heffernan E, Killeen RP, Mulready K, MacMahon M, Brady JJ, McKenna C, Muldowney C, Cassidy L, Walsh C, O'Rourke K, Tubridy N, McGuigan C, Fletcher JM, Hutchinson M., Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial., Multiple sclerosis journal - experimental, translational and clinical, 3, (3), 2017, p2055217317727296Journal Article, 2017, DOI
• O'Rourke M, Fearon U, Sweeney CM, Basdeo SA, Fletcher JM, Murphy CC, Canavan M, The pathogenic role of dendritic cells in non-infectious anterior uveitis., Experimental eye research, 2018, p121 - 128Journal Article, 2018, DOI
• 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
• Coleman MM, Basdeo SA, Coleman AM, Cheallaigh CN, Peral de Castro C, McLaughlin AM, Dunne PJ, Harris J, Keane J., All-trans Retinoic Acid Augments Autophagy during Intracellular Bacterial Infection., American journal of respiratory cell and molecular biology, 59, (5), 2018, p548-556Journal Article, 2018, DOI
• Dunne, Pádraic J., Lynch, Julie, Prihodova, Lucia, O'Leary, Caoimhe, Ghoreyshi, Atiyeh, Basdeo, Sharee A., Cox, Donal J., Breen, Rachel, Sheikhi, Ali, Carroll, Áine, Walsh, Cathal, McMahon, Geraldine, White, Barry, Burnout in the emergency department: Randomized controlled trial of an attention-based training program, Journal of Integrative Medicine, 2019Journal Article, 2019, DOI
• 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
• 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
• Ó Maoldomhnaigh C, Cox DJ, Phelan JJ, Malone FD, Keane J, Basdeo SA., The Warburg Effect Occurs Rapidly in Stimulated Human Adult but Not Umbilical Cord Blood Derived Macrophages., Frontiers in immunology, 12, 2021, p657261Journal Article, 2021, DOI
• Cahill C, O'Connell F, Gogan KM, Cox DJ, Basdeo SA, O'Sullivan J, Gordon SV, Keane J, Phelan JJ., The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG., International journal of molecular sciences, 22, (6), 2021Journal Article, 2021, DOI
• 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, DOI
• Murphy, D.M. and Mills, K.H.G. and Basdeo, S.A., The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research, Frontiers in Immunology, 12, (706583), 2021Journal Article, 2021, DOI , URL , TARA - Full Text
• 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
• Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH., Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity., Journal of immunology (Baltimore, Md. : 1950), 186, (10), 2011, p5738-5748Journal Article, 2011, 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, 2022Journal Article, 2022, 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), 2023Journal Article, 2023, DOI
• 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, p2898Journal Article, 2024, DOI
• Jameson G, Walsh A, Woods R, Batten I, Murphy DM, Connolly SA, Duffin E, O'Gallchobhair O, Nadarajan P, O'Connell F, Gleeson LE, Keane J, Basdeo SA, Human tissue-resident NK cells in the lung have a higher glycolytic capacity than non-tissue-resident NK cells in the lung and blood., Proceedings of the National Academy of Sciences of the United States of America, 2024Journal Article, 2024, 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, 2024Journal Article, 2024, DOI
• Brown K, Walsh A, Yennemadi A, O'Leary S, O'Sullivan M, Nadarajan P, Basdeo S, Leisching G, Keane J, Mycobacterium tuberculosis Induces Warburg Metabolism in Human Alveolar Macrophages: A Transcriptomic Analysis., American Journal of Respiratory Cell and Molecular Biology, 2025Journal Article, 2025, DOI
• Connolly, Sarah A.; Walsh, Aaron; Ledwith, Anna E.; McCarthy, Karen N.; O'Rourke, Sinead A.; Murphy, Dearbhla M.; Blasinska, Anna; Dunne, Aisling; Fletcher, Jean M.; Mills, Kingston H.G.; McManus, Ross; Sheedy, Frederick J.; Basdeo, Sharee A., BNT162b2 mRNA vaccination attenuates innate immune function in humans, Clinical Immunology, 276, 2025Journal Article, 2025, DOI
• Thong L, Sandby Thomas O, Ó Gallchobhair O, Duffin E, Yennemadi AS, Leisching G, Murphy DM, Nadarajan P, O'Connell F, O'Sullivan MP, Basdeo SA, Cox DJ, Keane J., Dexamethasone inhibits Mycobacterium tuberculosis-induced glycolysis but preserves antimicrobial function in primary human macrophages., Scientific Reports, 15, (1), 2025, p34310Journal Article, 2025, DOI
• Kevin Brown, Aaron M. Walsh, Anjali S Yennemadi, Dearbhla M Murphy, Sarah Conolly, Mary P. O"Sullivan, Sharee A. Basdeo, Seónadh M. O"Leary, Gina Leisching, Joseph Keane, HIV inhibits Warburg metabolism in human macrophages infected with Mycobacterium tuberculosis, 2025Journal Article, 2025, DOI
• Murphy DM, Batten I, O'Farrell A, Carlile SR, O'Rourke SA, Court C, Morris B, Leisching G, Jameson G, Connolly SA, Dyer AH, McGrath JP, McNally E, Basdeo SA, IFN-Y-induced trained immunity enhances killing of priority pathogens in healthy and genetically vulnerable individuals., JCI insight, 2026Journal Article, 2026, DOI
• Gráinne Jameson, Isabella Batten, Adam H. Dyer, C. Geoghegan, Moninne Murray, Niamh McDonnell, Dearbhla M Murphy, Sarah A. Connolly, Anne Marie McLaughlin, Cilian Ó Maoldomhnaigh, Laura E. Gleeson, Joseph Keane, Sharee A. Basdeo, Monocyte metabolic plasticity and cytokine production differentiate latent TB infection from active disease, Journal of Infection, 92, (6), 2026, p106755 - 106755, p106755-106755Journal Article, 2026, DOI
• Aaron M. Walsh, Emma Roycroft, Kate Hinchion, Sharee A. Basdeo, Frederick J. Sheedy, Fiona Crispie, Paul D. Cotter, Anne-Marie McLaughlin, Joseph Keane, Margaret Fitzgibbon, Laura E. Gleeson, Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution, Genome Medicine, 17, (1), 2025, p120 - 120, p120-120Journal Article, 2025, DOI
• Donal J Cox, Amy M. Coleman, Karl M Gogan, Pádraic J. Dunne, Sharee A. Basdeo, Joseph Keane, Vorinostat (SAHA) promotes innate and adaptive immunity to Mycobacterium tuberculosis, Access Microbiology, 2, (1), 2020Journal Article, 2020, DOI
• Lara S. Dungan, Stephen J. Lalor, Caroline E. Sutton, Sharee A. Basdeo, Jean M. Fletcher, Kingston H. G. Mills, CS05-6. Caspase-1"Processed Cytokines IL-1ß and IL-18 Promote IL-17 Production by and CD4 T Cells That Mediate Autoimmunity, Cytokine, 56, (1), 2011, p13 - 13, p13-13Journal Article, 2011, DOI
• Cilian Ó Maoldomhnaigh, Donal J Cox, Joseph Keane, Sharee A. Basdeo, P-450. Neonatal macrophages have an altered immunometabolic response to Mycobacterium tuberculosis which is modified by IFN-", IL-4 or lactate, 13, (Supplement_1), 2026Conference Paper, 2026, DOI
• Mary Canavan, Micheal A. O"Rourke, C. Orr, Sharee A. Basdeo, Jean M. Fletcher, Douglas J. Veale, Ursula Fearon, A1.08"CD141+ CLEC9A+ dendritic cells are enriched in an active state in the inflamedsynovium and contribute to synovial inflammation in rheumatoid arthritis, Annals of the Rheumatic Diseases, 75, 2016, pA3 - A4, pA3-A4Journal Article, 2016, DOI
• Cheryl M. Sweeney, Roisin Lonergan, Sharee A. Basdeo, Katie Kinsella, Lara S. Dungan, Sarah C. Higgins, Patrick J. Kelly, Lisa Costelloe, Niall Tubridy, Kingston H.G. Mills, Jean M. Fletcher, IL-27 mediates the response to IFN beta therapy in multiple sclerosis patients by inhibiting Th17 cells, Brain, Behavior and Immunity, 25, (6), 2011, p1170-1181Journal Article, 2011, DOI , URL , TARA - Full Text
• Lalor, S.J., Dungan, L.S., Sutton, C.E., Basdeo, S.A., Fletcher, J.M., Mills, K.H.G., Caspase-1-processed cytokines IL-1β and IL-18 promote IL-17 production by γδ and CD4 T cells that mediate autoimmunity, Journal of Immunology, 186, (10), 2011, p5738-5748Journal Article, 2011, DOI
• Jean M Fletcher, Sharee A Basdeo, Aideen C Allen and Padraic J Dunne, Therapeutic use of vitamin D and its analogues in autoimmunity, Recent Patents in Inflammation Allergy Drug Discovery, 6, (1), 2012, p22 - 34Review Article, 2012, DOI
• Allen AC, Kelly S, Basdeo SA, Kinsella K, Mulready KJ, Mills KH, Tubridy N, Walsh C, Brady JJ, Hutchinson M, Fletcher JM, A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers., Multiple sclerosis (Houndmills, Basingstoke, England), 18, (12), 2012, p1797 - 1800Journal Article, 2012, DOI

• DJ Cox, O Sandyby-Thomas, D Murphy, LE Gleeson, SA Basdeo, J Keane, Driving Resolution of Tuberculosis: Ifn-" Induced Plasticity in Human Alveolar Macrophages Can Be Resolved With IL-10: Implications for Macrophage Plasticity as a Therapeutic Target for Tuberculosis, American Thoracic Society, San Diego, USA, May 2024Conference Paper, DOI
• Sarah Connolly, Sharee A Basdeo, Defining the Role of Th17 Lineage Cells in People with COVID-19, Trinity Student Medical Journal, 2023Review Article
• Sharee Ann Basdeo, James Phelan, Donal Cox, Padraic Dunne, Joseph Keane, Sharee Ann Basdeo Check TCD e-journals IFN-gamma priming utilizes Warburg metabolism to increase human macrophage function and subsequently enhance polyfuctional cytokine production from T cells in response to Mycobacterium tuberculosis, Cytokines 2017, Japan, November 2017Conference Paper
• CO Maoldomhnaigh, D Cox, K McQuaid, K Gogan, S Basdeo, J Keane, Lactate improves killing of Mycobacterium tuberculosis in human macrophages, IRISH JOURNAL OF MEDICAL SCIENCE, Dublin, 2019, 2019Conference Paper, DOI

• Title

  COVID-19 vaccines enhance innate immune function to drive protective immune responses
  Summary

  The development of pathogen-specific immune memory relies not only upon antigen recognition by adaptive lymphocytes (B and T-cells to drive antibody production and cellular responses, respectively), but also upon stimulation of the innate immune system, including myeloid cells like DC dendritic cells DC)"s and macrophages to drive inflammation and antigen-presentation. Recently, memory-like properties have been ascribed to innate immune cells through a process termed "Trained Immunity" " the extent of its effector functions and its durability however, are still under investigation.
  Early recognised drivers of this pathway in myeloid cells were the TB-specific vaccine BCG and fungal cell-wall components, beta-glucans. However, it is likely that other adjuvants or combinations of adjuvants trigger similar responses. While this area of investigation has received interest for how it could be harnessed to drive heterologous responses by priming for later re-stimulation/activation in areas like infection resistance and cancer, how these
  effects on innate immune cell reprogramming including metabolic and epigenetic reprogramming, contribute to the normal activation of adaptive
  immune cells and the development of immune memory is less well described. In particular, how the various components of COVID-19 vaccines can enhance innate
  immune function, aside from immediate inflammatory activation but over the longer course of the immunization schedule has not been examined.
  Preliminary data from the Basdeo Group has examined monocytes derived from individuals vaccinated with the adenoviral vector-based Astra-Zeneca vaccine and
  found a long-term, durable increased expression of molecules associated with antigen-presentation and co-stimulation which was maintained up to 3-months post-vaccination.
  Unbiased screening for Trained Immunity-sensitive genes in macrophages taken from beta-glucan-treated animals in the Sheedy Lab also highlighted increased basal expression of a subset of genes associated with MHC processing and antigen presentation. We therefore propose that specific activation of innate immune cells can be employed not just to enhance innate responses to infection, but to optimally drive vaccine responses and the generation of specific-immune memory, through epigenetically reprogramming and imprinting myeloid cells leading to increased
  expression of genes associated with antigen processing and improved APC-
  function. This is particularly relevant during the current COVID-19 crisis as more vaccine candidates come on line and face problems with availability and suitability and as we move toward an era of heterologous vaccination in response to the imminent threat of vaccine-resistant viral variants.
  Funding Agency

  SFI-AIB COVID-19 SPP
  Date From

  September 2020
  Date To

  August 2023
• Title

  Defining the role of Th17 lineage cells in human pulmonary health and disease.
  Summary

  The immune responses in the lung tread a tightrope between mounting defensive inflammation against pathogens and maintaining the integrity of the delicate mucosal barrier. T cells play a crucial role in balancing appropriate and inappropriate inflammation and can exhibit a range of distinct behaviours in the lung. Therefore, the immune responses of T cells that live long term in the lung are thought to be important to the outcome of a pulmonary infection. Research largely focuses on the aberrant behaviour of immune cells in disease settings; however, it is becoming increasingly evident that there is paucity of information around what constitutes a healthy immune response in the lung. This project will focus on a population of T cells called Th17 cells which display extensive diversity and adaptability by exhibiting a spectrum of behaviours depending on the context of the immune response and the signals in the microenvironment. These cells have been implicated in lung pathologies including autoimmunity and infection leading to chronic inflammation. However, discreet members of this lineage are also known to be protective at mucosal sites. We hypothesise that Th17 lineage cells in healthy lungs maintain the integrity of the mucosal barrier and strike a balance in the immune response they generate and propagate through the complex cellular network of the lung tissue. However, these cells also have the ability to switch into more proinflammatory effector cells that cause damage and propagate intractable inflammation. This project aims to understand the behaviours of Th17 lineage cells that balance appropriate inflammation with maintaining barrier integrity in healthy lungs. We will examine the effects of the lung environment on human Th17 lineage cells using established in vitro models. In addition, we will determine the effects of Th17 lineage cell subpopulations on the lung environment, including their differential ability to propagate inflammation versus promoting resolution. Finally, this project will reuse existing data sets generated from human lung samples to determine a role for Th17 lineage subpopulations in mounting effective versus pathological immune responses in the lung. This project has the potential to create actionable knowledge in diverse contexts of respiratory diseases. Furthermore, it may contribute valuable understanding of how Th17 lineage cells behave in the lung and the signals promoting them to establish long term tissue resident memory cells that can mediate appropriate protection against infections. These data may therefore help to inform the design of inhaled vaccines for respiratory infectious diseases.
  Funding Agency

  TCD
  Date From

  September 2021
  Date To

  August 2025
• Title

  Defining the consequences of innate immune training on protective versus pathogenic T cell responses in patients with tuberculosis.
  Summary

  Tuberculosis (TB) ranks alongside HIV as the world's most deadly infectious disease, killing 1.5 million people every year. It is caused by the bacteria Mycobacterium tuberculosis (Mtb), which primarily infects people's lungs.
  Treating this disease is becoming more difficult due to antibiotic-resistant Mtb, therefore, scientists are developing ways to boost the immune system to kill Mtb more effectively.
  Two immune cells that play a prominent role in our ability to fight Mtb are alveolar macrophages (AM) and T cells. AM are the guardians of the lungs and encounter the bacteria first. They try to contain infection by eating and killing the bacteria, and then switching on T cells. However, Mtb can manipulate the AM and live inside it, causing TB disease.
  T cells are the generals of the immune system, helping to coordinate long term defence. However, in TB, these cells can be a double-edged sword; sometimes they can help clear the infection, but they can also cause collateral damage to the lungs.
  It was recently discovered that AM can be "trained" to increase their functions (similar to the way training improves an athlete's performance). This improves the AM's ability to kill bacteria. In addition, we have evidence to suggest this training will give clearer signals to the T cells, which will balance the immune response towards clearing the infection, rather than damaging the lungs.
  This project will compare different training regimens to see which best promotes the killing of Mtb and what affect the training has on T cell responses. By studying the different types of T cells that are activated during Mtb infection, we will determine which response may be harmful to the patient. By better understanding the human immune response during Mtb infection, we will be able to adjust it to help the patient recover from TB.
  Funding Agency

  Health Research Board
  Date From

  01 March 2020
  Date To

  28 February 2025
• Title

  Defining prolonged innate immune alterations in people post-acute infection to develop a high-risk, high-gain proposal for an ERC Starting Grant application.
  Summary
  Funding Agency

  TCD
  Date From

  01 Oct 2022
  Date To

  30 Sept 2023
• Title

  Myeloid memory and metabolic flexibility as a tractable target for host-directed therapies and monitoring treatment efficacy in people with Tuberculosis.
  Summary

  Tuberculosis (TB) remains a leading cause of mortality, with 1.25 million deaths and
  10.8 million new infections in 2023, including 1.2 million children. Despite being
  curable, TB continues to pose significant public health challenges in Ireland and
  globally, where rising incidence and multidrug-resistant (MDR) cases hinder progress
  toward the UN Goal of ending TB by 2030. A key barrier to effective clinical
  management is the absence of a biomolecular marker to monitor treatment efficacy"
  clinicians rely solely on fixed time-based regimens rather than biological indicators of
  cure.
  Our preliminary data identify monocyte immunometabolism as a promising biomarker
  of TB treatment response and disease resolution. Circulating monocytes from
  individuals with latent TB infection (TBI) and active TB disease (TBD) show distinct
  metabolic and phenotypic profiles. Mitochondrial dependency is reduced in both TBI
  and TBD compared with healthy controls but recovers with treatment. Moreover,
  metabolic flexibility in monocytes correlates with enhanced immune responsiveness
  to Mycobacterium tuberculosis, indicating that metabolic reprogramming underpins
  protective innate immune memory.
  By integrating patient-oriented research with translational immunology, we aim to
  define metabolic correlates of protection and therapeutic efficacy, advancing
  biomarker discovery and host-directed therapeutic strategies. Targeting myeloid cell
  metabolism offers a tractable route to enhance immune clearance, shorten treatment
  regimens, and expand options for MDR-TB.
  Ireland"and this team, based at the Trinity Translational Medicine Institute, colocated
  with the National Centre for TB Care and the National Mycobacteria
  Reference Laboratory at St James"s Hospital, now also home to the new Children"s
  Health Ireland hospital"is uniquely positioned to lead this work. Our research will
  longitudinally follow the TB treatment journey across the lifespan, encompassing
  infants, children, and adults. This project will deliver urgently needed biomolecular
  tools to guide clinical decision-making and inform the design of host-directed
  therapies to accelerate progress toward TB eradication.
  Funding Agency

  Health Research Board
  Date From

  01/03/2027
  Date To

  28/02/2030
• Title

  Defining how innate immune function is impacted long term in people who have had active Tuberculosis.
  Summary

  The Problem
  Tuberculosis (TB) is a complex disease caused by a bacteria called Mycobacterium tuberculosis (Mtb) and claims the lives of 1.4 million people annually. When a person is exposed to Mtb, their immune response may clear the infection asymptomatically, contain it in a dormant state (called latent TB) or it can grow and replicate inside the macrophage causing active TB disease.
  The gap in our knowledge
  TB doesn't play by the rules of the immunity to infection. If you have previously had active TB you are more likely to get sick again with TB than someone who has never had it before and we don't know why.
  Our proposed solution
  Our research team study the innate immune response to Mtb and have established ways to therapeutically boost a patient's own immune system to fight off the bug. We think that Mtb may alter the function of the innate immune response long term in people who have previously had TB. This altered function is a bit like a scar that is left after an injury and we propose that this may be the reason why people who have had TB are more vulnerable to getting TB again. We want to define the status of innate immune cells in people who have had TB compared with healthy people in order to determine if their innate immune responses are reprogrammed by the infection. This will enable us to design a therapy aimed at protecting these vulnerable people from contracting TB again.
  Funding Agency

  Health Research Board
  Date From

  September 2022
  Date To

  March 2025
• Title

  Defining inflexible macrophage metabolism as a correlate of harm and tractable target in patients with Tuberculosis
  Summary

  Tuberculosis (TB) remains a leading global cause of infectious mortality. Ireland has
  experienced a recent rise in TB incidence, including multi-drug-resistant disease. A
  major barrier to TB elimination is the reservoir of individuals with TB infection who are
  at risk of progressing to disease, particularly those with impaired early innate immune
  responses. Our converging evidence indicates that metabolic inflexibility in
  monocytes and macrophages"failure to undergo rapid bioenergetic
  reprogramming"is a unifying mechanism underlying susceptibility. This is seen
  across diverse high-risk groups, including people living with HIV (PLWH), patients
  receiving anti-TNF therapy, individuals with dysregulated type-I interferon (IFN-I)
  signalling, and smokers. Preliminary data from our collaborative group show i)IFN-I
  dysregulates glycolysis-dependent immunothrombosis to Mycobacterium tuberculosis
  (Mtb), ii)that anti-TNF therapy disrupts macrophage and airway-cell metabolic circuits
  essential for Mtb control, and iii)that human alveolar macrophages (AM) from
  smokers and PLWH exhibit impaired metabolic flexibility that can be restored through
  host-directed metabolic interventions.
  This collaborative programme will test the overarching hypothesis that metabolic
  reprogramming can repair innate immune defects driving vulnerability to Mtb.
  Three complementary project arms address distinct but mechanistically linked
  dimensions of susceptibility. Aim 1 investigates the IFN-I"Tissue Factor"glycolysis
  axis in TB and tests whether metabolic boosting restores immunothrombotic
  containment. Aim 2 defines how TNF blockade perturbs macrophage and airway-cell
  metabolic amplification circuits and assesses whether reprogramming reverses these
  defects. Aim 3 characterises AM metabolic inflexibility in smokers and PLWH, and
  evaluates AM-targeted metabolic interventions, including inhalable formulations.
  Harmonised proteomic profiling, RNA seq, immunothrombosis assays, functional
  macrophage infection models, and targeted metabolic modulators will identify shared
  metabolic vulnerability signatures and test pan-cohort efficacy of lead reprogramming
  compounds. The programme will establish innate metabolic inflexibility as a
  mechanistic determinant of TB susceptibility and deliver a translational framework for
  host-directed metabolic therapies, informing national policy and advancing Ireland"s
  contribution to global End TB strategies.
  Funding Agency

  Health Research Board
  Date From

  01/09/2027
  Date To

  31/08/2031
• Title

  Vorinostat as a host-directed therapy for Tuberculosis; manipulating epigenetics to boost macrophage function and promote polyfunctional T cell responses.
  Summary

  According to the WHO, tuberculosis (TB) ranks alongside HIV as the world"s most deadly
  infectious disease. The rapidly increasing incidences of multiple and extreme drug resistant
  cases are making TB very hard to treat and difficult to contain in society. Therefore,
  emerging strategies to treat TB by promoting the patient"s own immune system are currently
  under investigation. These host-directed therapies will be effective against antibiotic-resistant
  strains.
  Alveolar macrophages (AM) are the sentinels of the lungs, thus, are the first cells to
  encounter mycobacterium tuberculosis (Mtb). Upon infection, the AM becomes activated and
  switches on its effector functions to ingest and kill the bacteria. Mtb, however, is very
  effective at shutting off these effector functions so it can live and replicate inside the AM,
  causing active TB disease.
  The adaptive immune response plays a key role in clearing infections that overwhelm the
  initial innate immune response driven by the AM and other infiltrating macrophages.
  Moreover, the adaptive response produces immune memory which can recognise previously
  encountered bacteria and respond quickly against them if reinfection occurs. It is these
  memory responses that are required to produce effective vaccination and to stimulate the
  clearance of bacteria in infected patients.
  Preliminary data from our lab indicates that vorinostat, an FDA approved drug for cancer,
  may prove to be useful in boosting macrophage function and subsequent adaptive T cell
  function during Mtb infection. This project aims to determine the effects of treating human
  macrophages with vorinostat and to produce better, prolonged immune responses to Mtb.
  The ultimate goal of this research is to generate proof-of-concept data for the use of
  vorinostat as a host-directed therapy to treat antibiotic-resistant TB.
  Funding Agency

  Irish Research Council
  Date From

  1 Oct 2017
  Date To

  31 March 2020
• Title

  Inducing respiratory trained immunity for TB host defence in the human lung.
  Summary

  Tuberculosis (TB) is a leading cause of death from an infectious agent. Globally,
  there has been a marked increase in TB incidence and drug-resistant TB in the past
  two years. There is an urgent unmet clinical need for host-directed therapeutics and
  prophylactics capable of inducing effective respiratory immunity against the bacteria
  that causes TB; Mycobacterium tuberculosis (Mtb).
  Since the tissue resident alveolar macrophage (AM) is the first cell to encounter Mtb
  in the human lung, and the cell that becomes chronically infected leading to TB
  disease, supporting the immune function of this population, and the lung resident
  cells in proximity, is a rational therapeutic strategy to promote immune defence
  against Mtb infection. Myeloid cells from the bone marrow have a capacity to be
  `trained" towards enhanced host defence. Our recent work has shown that a COVID-
  19 adenovirus-vectored vaccine 'trained' monocytes towards enhanced non-specific
  immune responses to Mtb. Our collaborator showed that aerosolised delivery of an
  adenovirus vectored vaccine against Mtb elicited immunity in the lung whereas
  intramuscular vaccination did not. Evidence from murine models of respiratory
  mucosal adenovirus vaccination indicates that murine AM can be 'trained' resulting in
  enhanced immunity to bacterial infection mediated by improved kinetics of myeloid
  cell recruitment. However, a significant knowledge gap human remains as to whether
  tissue resident human AM can be trained to promote immunity to Mtb, and the
  mechanisms inducing and propagating trained immunity in the human lung.
  This project will be the first to define the induction of trained immunity in human AM
  through evidence of functional and phenotypic changes in the human AM,
  underpinned by metabolic and epigenetic reprogramming. These crucial data will
  define the human AM as a critical target for respiratory mucosal prophylactic or
  therapeutic vaccination, enabling the translation of trained immunity towards the
  global effort to `End TB".
  Funding Agency

  Health Research Board
  Date From

  01/03/2025
  Date To

  28/02/2028
• Title

  Reprogramming systemic and tissue resident innate immunity post infection to inhibit autoinflammatory events and disease
  Summary
  Funding Agency

  Enterprise Ireland
  Date From

  March 2023
  Date To

  February 2024

Clinical Trials and Interventions, Microbiology, Medical infection agents (incl. prions), Vaccines, Biochemistry and cell biology not elsewhere classified, Respiratory diseases, Infectious diseases, Public and Patient Involvement in Health Research, Medical, health and life sciences, Immunology, Basic Medicine and Life Sciences, Genomics, Metagenomics and transcriptomics, Proteomics and metabolomics, Clinical pharmacology and therapeutics, Infant and child health, Drug discovery, design and delivery, Immunology not elsewhere classified, Innate immunity, Neonatology, Medical biochemistry - lipids, Cellular immunology, Health equity, Medical bacteriology, Genetic immunology, Cardiovascular medicine and haematology, Medical biochemistry - proteins and peptides (incl. medical proteomics), Cell metabolism, Biomedical fluid mechanics, Medical biochemistry - carbohydrates, Clinical sciences research design, methodology, and analysis, Cellular interactions (incl. adhesion, matrix, cell wall), Molecular, biological, and multi-scale communications, Metabolic medicine, Medical biochemistry and metabolomics, Medical devices, Personalised medicine, Medical biochemistry - nucleic acids, Medical biochemistry - inorganic elements and compounds, Translational and applied bioinformatics, Immunogenetics (incl. genetic immunology), Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies), Medical microbiology, Medical biochemistry - amino acids and metabolites, Paediatrics,

• Nominated as Trinity's favorite Woman in Science 2023 (DU General Science Soc) March 2023
• Awarded Excellence in Research Supervision June 2023

• Irish Society of Immunology present
• European Society for Clinical Microbiology and Infectious Diseases present
• British Society of Immunology present