Smyth, Lesley - University of East London - School of Health, Sport and Bioscience

个人简介

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.

研究领域

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.

近期论文

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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.