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Dr. Sharee Basdeo
Assistant Professor, Clinical Medicine

Publications and Further Research Outputs

Peer-Reviewed Publications

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, 2023 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, 2022 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), 2021 Journal Article, 2021 DOI TARA - Full Text

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 Journal Article, 2021

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, p657261 Journal Article, 2021 DOI

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

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 Journal Article, 2020 TARA - Full Text URL 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, 2020 Journal Article, 2020 TARA - Full Text URL 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, 2019 Journal Article, 2019 DOI

Farver-Vestergaard, Ingeborg and O{\textquoteright, Mindfulness-based cognitive therapy in COPD: a cluster randomised controlled~trial, European Respiratory Journal, 51, (2), 2018 Journal Article, 2018 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 - 128 Journal Article, 2018 DOI

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, p548-556 Journal 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, 2018 Journal Article, 2018 URL TARA - Full Text DOI

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, p2055217317727296 Journal Article, 2017 DOI

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, 2017 Journal 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, 2016 Journal Article, 2016 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.e2 Journal Article, 2016 URL TARA - Full Text 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, p528-40 Journal Article, 2015 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 - 1800 Journal Article, 2012 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 - 34 Review Article, 2012

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, p1170-1181 Journal Article, 2011 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, p5738-5748 Journal Article, 2011 DOI

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, p5738-5748 Journal Article, 2011 DOI

Research Expertise

Projects

  • 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 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
    • Reprogramming systemic and tissue resident innate immunity post infection to inhibit autoinflammatory events and disease
  • Funding Agency
    • Enterprise Ireland
  • Date From
    • March 2023
  • Date To
    • February 2024
  • 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.
  • Funding Agency
    • TCD
  • Date From
    • 01 Oct 2022
  • Date To
    • 30 Sept 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
    • 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
    • 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

Recognition

Awards and Honours

Nominated Excellence in Research Supervision January 2023

Nominated as Trinity's favorite Woman in Science 2023 (DU General Science Soc) March 2023

Memberships

European Society for Clinical Microbiology and Infectious Diseases February 2021 – present

British Society of Immunology December 2010 – present

Irish Society of Immunology September 2010 – present