Frederick Sheedy
Ussher Assistant 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. This builds upon my established expertise in innate immunity, lipid metabolism and molecular regulation by miRNA. 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, fuelled my interest in macrophage-driven disease. My current work pioneers new lines of investigation in the emerging field of immunometabolism and macrophage function during diseases such as cancer and infection.

Publications and Further Research Outputs

Peer-Reviewed Publications

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 Journal Article, 2017

Ní Cheallaigh C, Sheedy FJ, Harris J, Muñoz-Wolf N, Lee J, West K, McDermott EP, Smyth A, Gleeson LE, Coleman M, Martinez N, Hearnden CH, Tynan GA, Carroll EC, Jones SA, Corr SC, Bernard NJ, Hughes MM, Corcoran SE, O'Sullivan M, Fallon CM, Kornfeld H, Golenbock D, Gordon SV, O'Neill LA, Lavelle EC, Keane J, A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling., Immunity, 44, (2), 2016, p368-79 Journal Article, 2016 URL TARA - Full Text

Gleeson, L.E., Sheedy, F.J., Metabolic reprogramming & inflammation: Fuelling the host response to pathogens, Seminars in Immunology, 28, (5), 2016, p450-468 Journal Article, 2016

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 Journal Article, 2016

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 Journal Article, 2016 URL DOI TARA - Full Text

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 Journal Article, 2015 TARA - Full Text DOI

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 Journal Article, 2015

Sheedy, F.J., Turning 21: Induction of miR-21 as a key switch in the inflammatory response, Frontiers in Immunology, 6, (JAN), 2015 Journal Article, 2015 TARA - Full Text

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 Journal Article, 2014

Sheedy, F.J., Moore, K.J., IL-1 signaling in atherosclerosis: Sibling rivalry, Nature Immunology, 14, (10), 2013, p1030-1032 Journal Article, 2013

Moore, K.J., Sheedy, F.J., Fisher, E.A., Macrophages in atherosclerosis: A dynamic balance, Nature Reviews Immunology, 13, (10), 2013, p709-721 Journal Article, 2013

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 Journal Article, 2013

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 Journal Article, 2011

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 Journal Article, 2011

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 Journal Article, 2011 DOI

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 Journal Article, 2011 DOI URL TARA - Full Text

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 Journal Article, 2011

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 Journal Article, 2010 DOI

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 Journal Article, 2010 URL DOI TARA - Full Text

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 Journal Article, 2009 URL DOI

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 Journal Article, 2008 URL DOI

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 Journal Article, 2007 DOI TARA - Full Text

Non-Peer-Reviewed Publications

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 Patent, 2014 URL

Research Expertise

Projects

  • 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

Keywords

Bacteriology and bacterial pathogenesis; Host, Pathogen interactions; Immune system; Immunochemistry and immunogenetics; Immunodeficiency diseases; Immunology, Immunotherapy; Infectious diseases; Innate immunology; Lipid metabolism; Metabolism and metabolic diseases; Molecular Biology; Regulatory methods of gene expression; RNA processing, stability and degradation; Tumour immunology and immunotherapy; Vaccines; Vascular Biology, Thrombosis

Recognition

Awards and Honours

Irish Heart Foundation Stroke Prevention Research Bursary Award 02/2017

Senior Research Fellow, Trinity College Dublin 01/2014

Researcher of the Year, Trinity Institute of Molecular Medicine 11/2013

Highest achieving undergraduate student in first year of novel BSc Genetics, UCC 06/2004

Memberships

Irish Society of Immunology 2014 – 2017

American Heart Association - ATVB Council 2010 – 2013

Trinity Biochemical Society 2005 – 2017