Dr. Frederick Sheedy
Associate Professor, Biochemistry
Biography
I recently established my independent research group within the School of Biochemistry & Immunology at Trinity College, Dublin (TCD), Ireland, examining macrophage function in health and disease. I pioneered miRNA research in the field of innate immunity during my graduate studies in the O'Neill Lab, resulting in a Nature Immunology first author publication and this emerging field was highlighted by a Nature Reviews Immunology article, which I co-wrote. I obtained a postdoctoral fellowship from the American Heart Association to study the molecular mechanisms of inflammation in disease at NYU. This transformative work was published in Nature Immunology and alongside my recent work on tuberculosis, funded by a Starting Investigator grant from Science Foundation Ireland, fueled my interest in macrophage-driven disease. My recent work published in Cell Reports, J Immunology and AJRCMB (as last author), has uncovered the regulation of anti-microbial function by metabolism and through multiple industrial partnerships with local food companies , I have begun to examine the potential for β-glucan training of immunity. I aim to use this to consolidate my research in the emerging area of innate immune training and how this can improve resistance to infection.
Publications and Further Research Outputs
Peer-Reviewed Publications
Horneck Johnston, C.J.H. and Ledwith, A.E. and Lundahl, M.L.E. and Charles-Messance, H. and Hackett, E.E. and O'Shaughnessy, S.D. and Clegg, J. and Prendeville, H. and McGrath, J.P. and Walsh, A.M. and Case, S. and Austen Byrne, H. and Gautam, P. and Dempsey, E. and Corr, S.C. and Sheedy, F.J., Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity, iScience, 27, (3), 2024
Burak, M.F. and Stanley, T.L. and Lawson, E.A. and Campbell, S.L. and Lynch, L. and Hasty, A.H. and Domingos, A.I. and Dixit, V.D. and HotamıŠlıgil, G.S. and Sheedy, F.J. and Dixon, A.E. and Brinkley, T.E. and Hill, J.A. and Donath, M.Y. and Grinspoon, S.K., Adiposity, immunity, and inflammation: interrelationships in health and disease: a report from 24th Annual Harvard Nutrition Obesity Symposium, June 2023, American Journal of Clinical Nutrition, 120, (1), 2024, p257-268
Case, S. and O'Brien, T. and Ledwith, A.E. and Chen, S. and Horneck Johnston, C.J.H. and Hackett, E.E. and O'Sullivan, M. and Charles-Messance, H. and Dempsey, E. and Yadav, S. and Wilson, J. and Corr, S.C. and Nagar, S. and Sheedy, F.J., β-glucans from Agaricus bisporus mushroom products drive Trained Immunity, Frontiers in Nutrition, 11, (1346706), 2024
O'Sullivan, M. and Dempsey, E. and Case, S. and Hackett, E.E. and Ledwith, A.E. and Prendeville, H. and O'Brien, T. and Lewis, F. and Murphy, D.M. and Yadav, S. and Wilson, J. and Corr, S.C. and Sheedy, F.J., Negative Regulation of Innate Immune Signaling by Components of the Button Mushroom Agaricus bisporus, Molecular Nutrition and Food Research, 67, (14), 2023
Drakeford, C. and Aguila, S. and Roche, F. and Hokamp, K. and Fazavana, J. and Cervantes, M.P. and Curtis, A.M. and Hawerkamp, H.C. and Dhami, S.P.S. and Charles-Messance, H. and Hackett, E.E. and Chion, A. and Ward, S. and Ahmad, A. and Schoen, I. and Breen, E. and Keane, J. and Murphy, R. and Preston, R.J.S. and Oâ Sullivan, J.M. and Sheedy, F.J. and Fallon, P. and Oâ Donnell, J.S., von Willebrand factor links primary hemostasis to innate immunity, Nature Communications, 13, (1), 2022
Al-Sayyar, A. and Hulme, K.D. and Thibaut, R. and Bayry, J. and Sheedy, F.J. and Short, K.R. and Alzaid, F., Respiratory Tract Infections in Diabetes â" Lessons From Tuberculosis and Influenza to Guide Understanding of COVID-19 Severity, Frontiers in Endocrinology, 13, (919223), 2022
James J. Phelan and Frederick J. Sheedy., Phagocyte metabolism: neutrophils have their cake but don't eat it., Trends in Immunology, 2021
Gleeson, L.E. and Roche, H.M. and Sheedy, F.J., Obesity, COVID-19 and innate immunometabolism, British Journal of Nutrition, 125, (6), 2021, p628-632
Gleeson, L.E., Roche, H.M., Sheedy, F.J., Running Title: Obesity, COVID-19 and Innate Immunometabolism, British Journal of Nutrition, 2020
Hackett, E.E., Sheedy, F.J., An Army Marches on Its Stomach: Metabolic Intermediates as Antimicrobial Mediators in Mycobacterium tuberculosis Infection, Frontiers in Cellular and Infection Microbiology, 10, 2020
Sheedy, F.J., Divangahi, M., Targeting immunometabolism in host defence against Mycobacterium tuberculosis, Immunology, 2020
Charles-Messance, H., Sheedy, F.J., Train to Lose: Innate Immune Memory in Metaflammation, Molecular Nutrition and Food Research, 2020
Charles-Messance, H., Mitchelson, K.A.J., De Marco Castro, E., Sheedy, F.J., Roche, H.M., Regulating metabolic inflammation by nutritional modulation, Journal of Allergy and Clinical Immunology, 146, (4), 2020, p706-720
Hackett, E.E., Charles-Messance, H., O'Leary, S.M., Gleeson, L.E., Muñoz-Wolf, N., Case, S., Wedderburn, A., Johnston, D.G.W., Williams, M.A., Smyth, A., Ouimet, M., Moore, K.J., Lavelle, E.C., Corr, S.C., Gordon, S.V., Keane, J., Sheedy, F.J., Mycobacterium tuberculosis Limits Host Glycolysis and IL-1ß by Restriction of PFK-M via MicroRNA-21, Cell Reports, 30, (1), 2020, p124-136.e4
Gleeson LE, O'Leary SM, Ryan D, McLaughlin AM, Sheedy FJ, Keane JM., Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium Tuberculosis Infection., American journal of respiratory cell and molecular biology, 2018
Hackett, E.E., Sheedy, F.J., MiR-21 alters circulating Treg function in vascular disease-hope for restoring immunoregulatory responses in atherosclerosis?, Annals of Translational Medicine, 5, (1), 2017
Ni Cheallaigh Cliona, Sheedy Frederick J., Shields Up: Systemic Protection Provided by microRNA-21 During Sepsis?, 45 , (7 ), 2017
Gleeson, L.E., Sheedy, F.J., Metabolic reprogramming & inflammation: Fuelling the host response to pathogens, Seminars in Immunology, 28, (5), 2016, p450-468
Gleeson LE, Sheedy FJ, Palsson-McDermott EM, Triglia D, O'Leary SM, O'Sullivan MP, O'Neill LA, Keane J, Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication., Journal of immunology (Baltimore, Md. : 1950), 196, (6), 2016, p2444-2449
Ouimet, M., Koster, S., Sakowski, E., Ramkhelawon, B., Van Solingen, C., Oldebeken, S., Karunakaran, D., Portal-Celhay, C., Sheedy, F.J., Ray, T.D., Cecchini, K., Zamore, P.D., Rayner, K.J., Marcel, Y.L., Philips, J.A., Moore, K.J., Mycobacterium tuberculosis induces the MIR-33 locus to reprogram autophagy and host lipid metabolism, Nature Immunology, 17, (6), 2016, p677-686
Ní Cheallaigh, C., Sheedy, F.J., Harris, J., Muñoz-Wolf, N., Lee, J., West, K., McDermott, E.P., Smyth, A., Gleeson, L.E., Coleman, M., Martinez, N., Hearnden, C.H., Tynan, G.A., Carroll, E.C., Jones, S.A., Corr, S.C., Bernard, N.J., Hughes, M.M., Corcoran, S.E., O'Sullivan, M., Fallon, C.M., Kornfeld, H., Golenbock, D., Gordon, S.V., O'Neill, L.A., Keane, J. Lavelle, E.C, A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling., Immunity, 44, (2), 2016, p368 - 379
Ouimet, M., Ediriweera, H.N., Mahesh Gundra, U., Sheedy, F.J., Ramkhelawon, B., Hutchison, S.B., Rinehold, K., Van Solingen, C., Fullerton, M.D., Cecchini, K., Rayner, K.J., Steinberg, G.R., Zamore, P.D., Fisher, E.A., Loke, P., Moore, K.J., MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis, Journal of Clinical Investigation, 125, (12), 2015, p4334-4348
Palsson-Mcdermott, E.M., Curtis, A.M., Goel, G., (...), Xavier, R.J., O'Neill, L.A.J. , Erratum: Pyruvate kinase m2 regulates hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in lps-activated macrophages (Cell Metabolism (2015) 21 (65-80)), 2015, - 347
Sheedy, F.J., Turning 21: Induction of miR-21 as a key switch in the inflammatory response, Frontiers in Immunology, 6, (JAN), 2015
Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, van den Bosch MW, Quinn SR, Domingo-Fernandez R, Johnson DG, Jiang J, Israelsen WJ, Keane J, Thomas C, Clish C, Vanden Heiden M, Xavier RJ, O'Neill LA, Pyruvate Kinase M2 Regulates Hif-1alfa Activity and IL-1ß Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages., Cell metabolism, 21, (1), 2015, p65-80
Ramkhelawon, B., Hennessy, E.J., Ménager, M., Ray, T.D., Sheedy, F.J., Hutchison, S., Wanschel, A., Oldebeken, S., Geoffrion, M., Spiro, W., Miller, G., McPherson, R., Rayner, K.J., Moore, K.J., Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity, Nature Medicine, 20, (4), 2014, p377-384
Fernandez-Hernando C, Moore KJ, Rayner KJ, Sheedy FJ, Suarez Y, 'miR-33 inhibitors and uses thereof to decrease inflammation', US Patent and Trading Office, PCT/US2012/035855 , 2014
Sheedy, F.J., Grebe, A., Rayner, K.J., Kalantari, P., Ramkhelawon, B., Carpenter, S.B., Becker, C.E., Ediriweera, H.N., Mullick, A.E., Golenbock, D.T., Stuart, L.M., Latz, E., Fitzgerald, K.A., Moore, K.J., CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation, Nature Immunology, 14, (8), 2013, p812-820
Sheedy, F.J., Moore, K.J., IL-1 signaling in atherosclerosis: Sibling rivalry, Nature Immunology, 14, (10), 2013, p1030-1032
Moore, K.J., Sheedy, F.J., Fisher, E.A., Macrophages in atherosclerosis: A dynamic balance, Nature Reviews Immunology, 13, (10), 2013, p709-721
Rayner, K.J., Sheedy, F.J., Esau, C.C., Hussain, F.N., Temel, R.E., Parathath, S., Van Gils, J.M., Rayner, A.J., Chang, A.N., Suarez, Y., Fernandez-Hernando, C., Fisher, E.A., Moore, K.J., Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis, Journal of Clinical Investigation, 121, (7), 2011, p2921-2931
Durrani O, Banahan K, Sheedy FJ, McBride L, Ben-Chetrit E, Greiner K, Vaughan RW, Kondeatis E, Hamburger J, Fortune F, Stanford MR, Murray PI, O'Neill LA, Wallace GR, TIRAP Ser180Leu polymorphism is associated with Behcet's disease., Rheumatology , 50, (10), 2011, p1760-5
Rayner, K.J., Esau, C.C., Hussain, F.N., McDaniel, A.L., Marshall, S.M., Van Gils, J.M., Ray, T.D., Sheedy, F.J., Goedeke, L., Liu, X., Khatsenko, O.G., Kaimal, V., Lees, C.J., Fernandez-Hernando, C., Fisher, E.A., Temel, R.E., Moore, K.J., Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides, Nature, 478, (7369), 2011, p404-407
O'Neill, L.A., Sheedy, F.J., McCoy, C.E., MicroRNAs: The fine-tuners of Toll-like receptor signalling, Nature Reviews Immunology, 11, (3), 2011, p163-175
Hennessy EJ, Sheedy FJ, Santamaria D, Barbacid M, O'Neill LA., Toll-like receptor 4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6, Journal of Biological Chemistry, 286, (29), 2011, p25531-9
Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, Johnson DS, Chen Y, O'Neill LA., Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21, Nature Immunology, 11, (2), 2010, p141-147
McCoy CE, Sheedy FJ, Qualls JE, Doyle SL, Quinn SR, Murray PJ, O'Neill LA, IL-10 inhibits miR-155 induction by Toll-like receptors., The Journal of Biological Chemistry, 285, (27), 2010, p20492-20498
Sheedy FJ, O'Neill LA., Adding fuel to fire: microRNAs as a new class of mediators of inflammation., Annals of the Rheumatic Diseases, 67 , (Suppl 3), 2009, piii50 - iii55
Sheedy FJ, Marinou I, O'Neill LA, Wilson AG., The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to or severity of rheumatoid arthritis., Ann Rheum Dis., 2008
Sheedy F. and O'Neill L.A., The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling, Journal of Leukocyte Biology, 82, (2), 2007, p196-203
Research Expertise
Projects
- Title
- Mushroom digestion as a model to re-define gut-immune system cross-talk via Innate Immune Training
- Funding Agency
- Enterprise Ireland
- Date From
- March 2020
- Date To
- March 2022
- Title
- Wellmune trains monocytes to increase innate immune memory & resistance
- Funding Agency
- Enterprise Ireland
- Date From
- 01/06/2018
- Date To
- 31/05/2020
- Title
- Targeting microRNA to drive a successful host response to Mycobacterium tuberculosis
- Funding Agency
- Science Foundation Ireland
- Date From
- 09/2014
- Date To
- 09/2018
- Title
- Measuring monocyte function as a marker of cardiovascular disease and immune activation
- Summary
- Atherosclerosis, a leading cause of cardiovascular disease, is triggered by recruitment of macrophages to areas of lipid deposition along vessel walls. The macrophages are recruited as precursor monocytes and differentiate locally to proinflammatory macrophages. Evidence suggests the type of monocyte recruited is affected by numerous factors. This project proposes to develop technologies to profile monocyte precursors in circulation by examining key mRNA and protein expression as biomarkers. This can be applied to approaches to monitor monocytes in disease susceptible patients.
- Funding Agency
- Irish Heart Foundation
- Date From
- 02/2017
- Date To
- 02/2018
- Title
- Metabolic control of tumor associated macrophage reprogramming by microRNA-21
- Funding Agency
- Irish Research Council
- Date From
- 01/10/2017
- Date To
- 30/09/2021
- Title
- Sensing of lipids on macrophages by CD36 alters tuberculosis immune responses
- Funding Agency
- Wellcome Trust/TCD
- Date From
- 01/06/2017
- Date To
- 31/05/2022
- Title
- IFN-gamma inhibits the maturation of anti-inflammatory microRNAs during macrophage activation
- Funding Agency
- Irish Research Council
- Date From
- 01/10/2019
- Date To
- 30/09/2021
- Title
- Diet, Immune Training & Metabolism
- Funding Agency
- SFI
- Date From
- June 2020?
- Date To
- June 2025?
- Title
- Improving anti-viral immunity through Innate Immune Training
- Funding Agency
- Irish Research Council
- Date From
- 01/09/2021
- Date To
- 31/08/2025
Recognition
Awards and Honours
Trinity Innovation Award - Industry Engagement
Provost PhD Award
Trinity Innovation Awards - short-listed in Industry Engagement
Irish Heart Foundation Stroke Prevention Research Bursary Award
Senior Research Fellow, Trinity College Dublin
Researcher of the Year, Trinity Institute of Molecular Medicine
Highest achieving undergraduate student in first year of novel BSc Genetics, UCC
Memberships
Irish Society of Immunology
European Federation of Immunology Societies
American Heart Association - ATVB Council
Trinity Biochemical Society