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Dr Lesley Smyth

Senior Lecturer of Immunology

Infection and Immunity, Health, Sport and Bioscience



    I started my scientific pathway at the University of Glasgow where I studied Immunology for my BSc degree. After a brief spell at Yale University, I embarked on a PhD at Edinburgh University studying the mechanisms behind immunological tolerance to milk proteins. I then moved to London where I worked at the National Institute for Medical Research investigating the signaling pathways involved in positive and negative thymic T cell selection. From there I   changed course slightly to work on endothelial cells and the role anti-apoptotic molecules play, with regards to protecting these cells from immune responses, during transplantation. Continuing within the transplantation field, I moved to King’s College London working with Profs Robert Lechler and Giovanna Lombardi. There I continued my research into immune regulation investigating the use of tolerogenic dendritic cells, as well as regulatory T cells, as cellular therapies to induce transplant tolerance. In addition, my other research interests was the intercellular transfer of information between cells and its implications in both a viral and transplant setting. This led to the discovery that viral peptide:MHC class 1 MHC molecules are exchanged between professional antigen-presenting cells highlighting a novel mechanism for spreading antigen during viral infections. In addition, I also investigated how regulatory T cells work and published that these cells can release extracellular vesicles that have immune modulatory properties.

    Postgraduate Certificate in Academic Practice in Higher Education

    Overview




    My current research focuses on the intercellular transfer of molecules between cells of the immune system with specific reference to immune regulation. I am investigating the role of exosomes released by regulatory T cells in controlling immune responses with an outlook to using these vesicles as a possible immunotherapy reagent.


    Collaborators

    • test

    Research

    Diversity of gut microflora is required for the generation of B cells with regulatory properties in a skin graft model. Alhabbab R, Blair P, Elgueta R, Stolarczyk E, Marks E, Becker PD, Ratnasothy K, Smyth L, Safinia N, Sharif-Paghaleh E, O'Connell S, Noelle RJ, Lord GM, Howard JK, Spencer J, Lechler RI, Lombardi G. Sci Rep. 2015 Jun 25;5:11554. doi: 10.1038/srep11554.

    Smyth LA, Hervoute C, Hayday T, Becker PD, Ellis R, Lechler RI, Lombardi G and Klavinskis LS (2012).

    Acquisition of MHC:peptide complexes by dendritic cells contributes to viral immunity in vivo. J Immunol 189: 2247-82.

    Peng Q, Li K, Smyth L, Wang N, Xin G, Meader L, Lu B, Sacks SH and Zhou W (2012). Additive effect of C3aR and C5aR deficiency in protecting mice from renal ischaemia reperfusion injury. J Am Soc Nephro 23: 1474-85.

    M Buckland, L Smyth, R Lechler and Giovanna Lombardi. (2012). Prospects for the induction of transplant tolerance using dendritic cells in Immunological Barriers to Regenerative Medicine; 257-279.

    Sharif-Paghaleh E, Sunassee K, Tavare R, Ratnasothy K, Koers A, Ali N, Alhabbab R, Blower PJ Lechler RI, Smyth LA*, Mullen G*, Lombardi G*. (2011). In vivo SPECT reporter gene imaging of regulatory T cells. PLoS One 6 (10): e25857. * Joint last authors

    JYS Tsang, K Ratnasothy, D Li, Y Chen, R P Bucy, K F Lau, L Smyth, G Lombardi, R Lechler and P K Hang Tam. (2011). The potency of allospecific Tregs appears to correlate with T cell receptor functional avidiy. Am J Transp 11: 1610-20.

    Lombardi G, Sagoo P, Scotta C, Fazekasova H, Smyth L, Tsang J, Afzali B, Lechler R. (2011). Cell therapy to promote transplant tolerance: a winning strategy? Immunotherapy 3 (4 Suppl):28-31.

    Smyth L.A., Harker N., Turnbull W., El-Doueik H., Klavinski L., Lombardi G and Lechler RI. (2008). The Relative efficiency of acquisition of MHC:peptide complexes and cross-presentation depends on dendritic cell type.

    J. Immunol. 181: 3212-20.

    Smyth L.A., Afzali B., Tsang J., Lombardi G and Lechler R.I. (2007). Intercellular Transfer of MHC and Immunological Molecules: Molecular Mechanisms and Biological Significance. Am J Transp 7: 1442–1449.

    Kapustin AN, Kalinina N, Lopatina T, Davidson SM, Iraci N, Tamkovich S, Smyth L, Ter-Ovanesyan D, Evtushenko EG, Savelieva O, Bertazzo S, Aushev V, Dragovic R, Gracia T, Heck M, Parfyonova YV, Shanahan CM, Tkachuk V.UK-Russian Researcher Links Workshop:extracellular vesicles – mechanisms of biogenesis and roles in disease pathogenesis, M. V. Lomonosov Moscow State University, Moscow, Russia, 1-5 March 2015. J. Extracell. Vesicles. 2015 May 14;4:28094. doi: 10.3402/jev.v4.28094. eCollection 2015.

    Smyth LA., Herrera OB., Goldshayan D., Lombardi G and Lechler RI. (2006). A novel pathway of antigen presentation by dendritic and endothelial cells; implications for allorecognition and infectious diseases. Transplantation 82(1 suppl): S15-8.

    Smyth LA., Brady HJ. (2005). cMet and Fas receptor interaction inhibits death-inducing signaling complex formation in endothelial cells. Hypertension. 46: 100-6.

    Smyth LA., Ardouin L., Williams O., Norton T., Tybulewitz V and Kioussis D. (2002). Inefficient clustering of tyrosine-phosphorylated proteins at the immunological synapse in response to an antagonist peptide. Eur. J. Immunol. 32: 3386-3394.

    Reynolds LF., Smyth LA., Norton T., Freshney N., Downward J., Kioussis D and Tybulewicz VLJ. (2002). Vav1 transduces T cell receptor signals to the activation of phospholipase C-g1 via phosphoinositide 3-kinase-dependent and -independent pathways. J. Exp. Med 195: 1103-14.

    Van Laethem F., Baus E., Smyth LA., Andris F., Bex F., Urbain J., Kioussis D and Leo O. (2001). Glucocorticoids attenuate T cell receptor signaling. J. Exp. Med 193; 803-14.

    Smyth LA., Reynolds L., Tyrrell R., Williams O., Norton T., Schumacher T., Tybulewicz T., Ley SC and Kioussis D. (1999) Signaling in primary thymocytes after presentation of altered peptide ligands by antigen-presenting cells or MHC-peptide tetramers. Cold. Spring. Harb. Symp. Quant. Biol 64: 275-81.

    Smyth LA., Williams O., Huby RD., Norton T., Acuto O., Ley SC and Kioussis D. (1998). Altered peptide ligands induce quantitatively but not qualitatively different intracellular signals in primary thymocytes. Proc. Natl. Acad. Sci. USA 95: 8193-8.

    Tarazona R., Williams O., Moskophidis D., Smyth LA., Tanaka Y., Wack A., Mamalaki C and Kioussis D. (1998). Susceptibility and resistance to antigen-induced apoptosis in the thymus of transgenic mice. J. Immunol. 160: 5397-403.

    Smyth LA., Williams O., Ley S and Kioussis D. (1997). Altered peptide ligand (APL) signalling in primary thymocytes. Immunology Letters 56: 234.

    Smyth LA and Ansell, J. (1994). Immunological tolerance to a mammary gland-specific transgenic protein. Immunology Letters 40.

    Agarwal A, Tung S, Fanelli G, Letizia M, Boardman D, Lechler R, Lombardi G and Smyth LA. Regulatory T cell derived Exosomes: possible therapeutic and diagnostic tools in transplantation. (2014). Front Immunol, 5 (5): 555.

    Smyth L., Howell, M and Crispe, I.N. (1992). Self-reactivity and the expression of memory markers vary independently in the MRL-Mp +/+ and MRL-Mp-lpr/lpr mice. Developmental Immunology 2: 309-318.

    Richardson MD., Smyth LA and Shankland GS. (1991). Stimulation of the human neutrophil phagocytosis of Candida albicans by a b-glutan synthase inhibitor Cilofungin. FEMS Microbiology Immunology 76: 299-304.

    Moreau A, Blair P A, Chai JG, Ratnasothy K, Stolarczyk E, AlhabbabR, RackhamCL, Jones PM, Smyth LA, ElguetaR, HowardJK, Lechler RI, Lombardi G. Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival. (2014) Eur J Immunol, 45: 843-53.

    Smyth LA, Boardman D, Tung S, Lechler RI and Lombardi G. MicroRNA affect dendritic cell function and phenotype (2014). Immunology 144: 197-205.

    Sharif-Paghaleh E, Leech J, Sunassee K, Ali N, Lechler RI, Smyth LA *, Lombardi G *, Mullen GE *. (2014) SPECT/CT tracking of 99mTc-HMPAO labelled CD4+ T cells in a dendritic cell vaccine murine model. Eur J Immunol 44: 2188-91. * Joint last author

    Smyth LA, Ratnasothy K, Tsang JY, Boardman D, Warley A, Lombardi G and Lechler RI. (2013). CD73 expression on extracellular vesicles derived from CD4+CD25+ FoxP3+ T cells contributes to their regulatory function. Eur J Immunol 43: 2430-40.

    Smyth LA, Ratnasothy K, Moreau A Alcock S, Sagoo P, Meader L Tanriver Y, Buckland M, Lechler R, and Lombardi G. (2013). Tolerogenic dendritic cells risk sensitisation in vivo due to processing and presentation by recipient antigen-presenting cells. J Immunol 190: 4848-60.

    Leech J M, Sharif-Paghaleh E, Maher J, Livieratos L, Lechler R I, Mullen G E*, Lombardi G * and Smyth LA. *.(2013). Whole body imaging of adoptively transferred T cells using MRI, SPECT and PET techniques, with a focus on regulatory T cells. Clin Exp Immunol 172: 169-77 * Joint last authors.

    Publications

    RoseTrees Trust Grant

    Funding

    2005-2015



    Research Fellow, MRC Centre for Transplantation, King’s College London, UK.
    2000-2005




    Senior Postdoctoral Research Associate, Department of Molecular Haematology and Cancer Biology, ICH, London
    1995-2000




    Postdoctoral Research Associate, Department of Molecular Immunology, National Institute for Medical Research, London.
    1991-1995



    PhD, University of Edinburgh.
    1990-1991



    Research associate, Immunobiology Department, Yale University, USA.
    1989-1989




    Research Technician, Department of Medical Mycology, University of Glasgow.
    1986-1990




    BSc (Hons) Immunology


    Exosomes and Immune Regulation

    Interests

    Portfolio




    BS6005 Clinical Microbiology and Immunology
    BS7005 Biomedical Immunology
    BS7007
    BS5005
    BS5009
    BS6003
    BS6009

    Module Leader for BS7005 Biomedical Immunology
    Member of the British Society for Immunology
    Member of the International Society for Extracellular Vesicles
    Associate Fellow of the Higher Education Academy (2015)
    Visiting Lecturer at KCL

    Teaching