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Guarda Greta, SNF Assistant Professor


 

Biography

Greta Guarda studied Molecular Biology at the University of Zurich and at the Swiss Federal Institute of Technology. She carried out her PhD work on T cell trafficking under the supervision of Federica Sallusto and Antonio Lanzavecchia at the Institute for Research in Biomedicine, Bellinzona. In 2007, she joined the group of Jürg Tschopp at the University of Lausanne as a post-doctoral fellow, and focused her research on NOD-like receptors in the context of inflammasome function. She was appointed senior lecturer in 2010 and Assistant Professor funded by the Swiss National Science Foundation in 2012. Her current research focuses on the function of NOD-like receptors that are highly expressed, but poorly characterized, in adaptive immune cells.

Research Interests

PATTERN RECOGNITION RECEPTORS IN INNATE AND ADAPTIVE IMMUNITY

In innate immune cells, the expression of pattern recognition receptors (PRRs), such as NOD-like receptors (NLRs), is crucial for early detection of endogenous stress signals or infections. However, certain NLRs are highly expressed by T lymphocytes, an aspect that has been largely overlooked. It is possible that these PRRs may provide T lymphocytes with functions resembling that of innate immune cells. Alternatively, they might exert novel functions in roles more traditionally associated with adaptive immune system pathways.

One focus of our research is the study of NLRC5, an emerging NLR family member. By using Nlrc5-deficient mice, we recently showed that NLRC5 is not involved in innate sensing, but acts instead as a transcriptional regulator of major-histocompatibility complex (MHC) class I, particularly in lymphocytes (Staehli et al., The Journal of Immunology, 2012; Ludigs et al., Plos Genetics, 2015). Currently, we are interested in delineating the molecular aspects of underlying NLRC5 activity and its implications in infection and malignant transformation.
 

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As anticipated by our data on NLRC5, we expect that a detailed analysis of NLR function in adaptive immune cells will reveal unexpected aspects of their signaling, or highlight unappreciated innate features of T lymphocytes. Both scenarios would be equally innovative and may provide us with new opportunities for therapeutic intervention.

Key words: NOD-like receptors (NLRs); NLRC5; MHC class I; transcriptional regulation; adaptive immunity; T cells; innate immunity; NK cells; infection; tumor

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2015 |  2013 |  2012 |  2011 |  2010 |  2009 |  2008 |  2007 |  2005 |  Thèses (doctorat) | 
 

2015
Ludigs K., Seguín-Estévez Q., Lemeille S., Ferrero I., Rota G., Chelbi S., Mattmann C., MacDonald H.R., Reith W., Guarda G., 2015. NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module. Plos Genetics 11(3) pp. e1005088. [DOI] [Web of Science] [Pubmed]
2013
Dostert C., Ludigs K., Guarda G., 2013. Innate and adaptive effects of inflammasomes on T cell responses. Current Opinion in Immunology 25(3) pp. 359-365. [DOI] [Web of Science] [Pubmed]
Jankovic D., Ganesan J., Bscheider M., Stickel N., Weber F.C., Guarda G., Follo M., Pfeifer D., Tardivel A., Ludigs K. et al., 2013. The Nlrp3 inflammasome regulates acute graft-versus-host disease. Journal of Experimental Medicine 210(10) pp. 1899-1910. [DOI] [Web of Science] [Pubmed]
Kolly L., Busso N., von Scheven-Gete A., Bagnoud N., Moix I., Holzinger D., Simon G., Ives A., Guarda G., So A. et al., 2013. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production. Journal of Allergy and Clinical Immunology 131(6) pp. 1635-1643. [DOI] [Web of Science] [Pubmed]
Michallet M.C., Rota G., Maslowski K., Guarda G., 2013. Innate receptors for adaptive immunity. Current Opinion in Microbiology 16(3) pp. 296-302. [DOI] [Web of Science] [Pubmed]
Neerincx A., Castro W., Guarda G., Kufer T.A., 2013. NLRC5, at the Heart of Antigen Presentation. Frontiers in Immunology 4 p. 397. [DOI] [Pubmed]
Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., Guarda G., Tian Z., Tschopp J., Zhou R., 2013. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity 38(6) pp. 1154-1163. [DOI] [Web of Science] [Pubmed]
2012
Gross O., Yazdi A.S., Thomas C.J., Masin M., Heinz L.X., Guarda G., Quadroni M., Drexler S.K., Tschopp J., 2012. Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36(3) pp. 388-400. [DOI] [Web of Science] [Pubmed]
Kupz A., Guarda G., Gebhardt T., Sander L.E., Short K.R., Diavatopoulos D.A., Wijburg O.L., Cao H., Waithman J.C., Chen W. et al., 2012. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8⁺ T cells. Nature Immunology 13(2) pp. 162-169. [DOI] [Web of Science] [Pubmed]
Ludigs K., Parfenov V., Du Pasquier R.A., Guarda G., 2012. Type I IFN-mediated regulation of IL-1 production in inflammatory disorders. Cellular and Molecular Life Sciences 69(20) pp. 3395-3418. [DOI] [Web of Science] [Pubmed]
Staehli F., Ludigs K., Heinz L.X., Seguín-Estévez Q., Ferrero I., Braun M., Schroder K., Rebsamen M., Tardivel A., Mattmann C. et al., 2012. NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by cytotoxic T cells. Journal of Immunology 188(8) pp. 3820-3828. [DOI] [Web of Science] [Pubmed]
Vince J.E., Wong W.W., Gentle I., Lawlor K.E., Allam R., O'Reilly L., Mason K., Gross O., Ma S., Guarda G. et al., 2012. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36(2) pp. 215-227. [DOI] [Web of Science] [Pubmed]
2011
Gross O., Thomas C.J., Guarda G., Tschopp J., 2011. The inflammasome: an integrated view. Immunological Reviews 243(1) pp. 136-151. [DOI] [Web of Science] [Pubmed]
Guarda G., Braun M., Staehli F., Tardivel A., Mattmann C., Förster I., Farlik M., Decker T., Du Pasquier R.A., Romero P. et al., 2011. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34(2) pp. 213-223. [DOI] [Web of Science] [Pubmed]
Guarda G., Yazdi A.S., D'Ombrain M.C., Drexler S.K., 2011. Acute gout: The inflammasome. Current Rheumatology Reviews 7(2) pp. 132-140.
Guarda G., Zenger M., Yazdi A.S., Schroder K., Ferrero I., Menu P., Tardivel A., Mattmann C., Tschopp J., 2011. Differential expression of NLRP3 among hematopoietic cells. Journal of Immunology 186(4) pp. 2529-2534. [DOI] [Web of Science] [Pubmed]
Rebsamen M., Vazquez J., Tardivel A., Guarda G., Curran J., Tschopp J., 2011. NLRX1/NOD5 deficiency does not affect MAVS signalling. Cell Death and Differentiation 18(8) p. 1387. [DOI] [Web of Science] [Pubmed]
2010
Guarda G., So A., 2010. Regulation of inflammasome activity. Immunology 130(3) pp. 329-336. [DOI] [Web of Science] [Pubmed]
Yazdi A.S., Guarda G., D'Ombrain M.C., Drexler S.K., 2010. Inflammatory caspases in innate immunity and inflammation. Journal of Innate Immunity 2(3) pp. 228-237. [DOI] [Web of Science] [Pubmed]
Yazdi A.S., Guarda G., Riteau N., Drexler S.K., Tardivel A., Couillin I., Tschopp J., 2010. Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β. Proceedings of the National Academy of Sciences of the United States of America 107(45) pp. 19449-19454. [DOI] [Pubmed]
2009
Dostert C., Guarda G., Romero J.F., Menu P., Gross O., Tardivel A., Suva M.L., Stehle J.C., Kopf M., Stamenkovic I. et al., 2009. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PloS one 4(8) pp. e6510. [Document] [DOI] [Web of Science] [Pubmed]
Guarda G., Dostert C., Staehli F., Cabalzar K., Castillo R., Tardivel A., Schneider P., Tschopp J., 2009. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature 460(7252) pp. 269-273. [DOI] [Web of Science] [Pubmed]
2008
Lozza L., Rivino L., Guarda G., Jarrossay D., Rinaldi A., Bertoni F., Sallusto F., Lanzavecchia A., Geginat J., 2008. The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells. European Journal of Immunology 38(1) pp. 30-39. [DOI] [Web of Science] [Pubmed]
Martín-Fontecha A, Guarda G, Lanzavecchia A., Sallusto F., 2008. Activated lymph nodes recruit blood borne NK cells and effector T cells: implications for adaptive T cell responses. Current Immunology Reviews 4(1) pp. 20-27. [DOI]
Martín-Fontecha A., Baumjohann D., Guarda G., Reboldi A., Hons M., Lanzavecchia A., Sallusto F., 2008. CD40L+ CD4+ memory T cells migrate in a CD62P-dependent fashion into reactive lymph nodes and license dendritic cells for T cell priming. Journal of Experimental Medicine 205(11) pp. 2561-2574. [DOI] [Web of Science] [Pubmed]
2007
Guarda G., Hons M., Soriano S.F., Huang A.Y., Polley R., Martín-Fontecha A., Stein J.V., Germain R.N., Lanzavecchia A., Sallusto F., 2007. L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells. Nature Immunology 8(7) pp. 743-752. [DOI] [Web of Science] [Pubmed]
2005
Melkko S., Sobek J., Guarda G., Scheuermann J., Dumelin C.E., Neri D., 2005. Encoded self-assembling chemical libraries. CHIMIA 59(11) pp. 798-802. [DOI] [Web of Science]
Phd thesis
Ludigs K., 2014. On the transcriptional role of NLRC5 and the function of NLRC5-driven MHC class I expression in the immune system. 113 p., Université de Lausanne, Faculté de biologie et médecine, Guarda G. (dir.).
Staehli F., 2011. Immune regulation and function of the NOD-like receptors NLRC5 and NLRP3. 123 p., Université de Lausanne, Faculté de biologie et médecine, Guarda G., Thome-Miazza M. (dir.).
Guarda G., 2007. Generation and function of mouse central memory and effector memory T cells. 47 p., Université de Lausanne, Faculté de biologie et médecine, Acha-Orbea H. (dir.).
 
 
 
 
 
 
 
Person Position Contact
Wilson Castro Ph.D student Unisciences
Sonia Chelbi Postdoctoral fellow Unisciences
Anh Thu Dang Ph.D student Unisciences
Kristina Ludigs Postdoctoral fellow Unisciences
Leonor Morgado Laboratory support Unisciences
Giorgia Rota Ph.D student Unisciences
Kevin Osterheld Masters student
Damien Cohen Masters student
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Contact

Guarda_photo.jpg

Greta Guarda

greta.guarda@unil.ch

Tel: +41 21 692 5768

Chemin des Boveresses 155 - CH-1066 Epalinges  - Switzerland  -  Tel. +41 21 692 5700  -  Fax +41 21 692 5705
Swiss University