Philippe Sansonetti
 | Bio: | My scientific approaches have been influenced by the dual need to decipher infection as microbe-cell cross talks, and to analyse infectious diseases in an integrative dimension encompassing host responses. On these bases, I have also tried to develop a rational approach for the design of bacterial vaccines. This reflects my training in basic research at Institut Pasteur and in internal medicine in Paris hospitals. In the late seventies, I selected invasive pathogens that recapitulate all the interaction steps, and pioneered the field in establishing Shigella flexneri and Listeria monocytogenes as models by combining genetics and development of cell assay sytems. Discovery of the Shigella virulence plasmid encoding cell invasion and reconstruction of a fully virulent Shigella from Escherichia coli K12, demonstration that Shigella escape in the cell cytoplasm, development of the first transposon mutagenesis in L. monocytogenes demonstrating the pathogenic role of listeriolysin, and demonstration of epithelial cell invasion by L. monocytogenes, are generally considered landmarks that influenced development of the field of molecular and cellular pathogenesis of bacterial infections. These early contributions convinced me of the strong potential of applying a multidisciplinary approach to the field, interfacing genetics, biochemistry, and soon cell biology, immunology and experimental medicine in a way that became a sort of paradigm. This generated three discoveries that were key to the making of Cellular Microbiology: actin polymerisation in entry of Shigella into epithelial cells, actin-based intracellular motility of Shigella, and Shigella killing macrophages by pro-inflammatory apoptosis, unexpectedly due to activation of caspase-1, an anticipation of the recognition of inflammasome. We then dissected the signalling pathways triggered by Shigella while invading epithelial cells, participating to emergence of the concept of Type III secretion. On the global scale of tissue infection and immunological responses, we showed the need for Shigella to elicit inflammation to disrupt the epithelial barrier. In the last 10 years, we have promoted two important novel concepts: (i) intracellular sensing of bacteria leading to the discovery of Nod molecules as cytosolic sensors, and identification of bacterial muropeptides as their proinflammatory agonists. This has now become a lively field that touches upon a large array of inflammatory diseases, and the concept of “danger signalling”. (ii) Identification of Shigella effectors regulating the host innate response. This has allowed to decipher a bacterial “cat & mouse” strategy focussed on manipulating ubiquitination of key host regulatory molecules, and to demonstrate for the first time, that bacteria can subvert the host innate response through epigenetic regulation involving manipulation of the histone code. A clear example is our recent demonstration that Shigella can regulate expression of epithelial antimicrobial peptides at the transcriptional level.
All this basic bacground has been a knowledge platform to design novel vaccine strategies against Shigella infection. The rational attenuation of major serotypes such as S. flexneri 2a and S. dysenteriae 1 has provided two orally-delivered, live attenuated candidates which have now undergone phase 1 and 2 clinical trials with promising results, even though major issues remain regarding differences in colonization and immunogenicity in populations living in industrialized or endemic areas, and serotype-specificity of protection. STOPENTERICS, under my coordination, is expected to addres these key - but complex - issues for both Shigella and ETEC vaccine development. Novel strategies will be developed, such as the discovery of new cross-protective antigens, the enhancement of antigenicity of key candidate molecules (i.e. ETEC ST toxin), and the development of a new generation of conjugate Shigella vaccine based upon synthetized surface sugars conjugated to virulence-related proteins.
Recently, thanks to the award of a European research Council Advanced Grant, I have started a novel project addressing the role of the gut microbiota in the development/maturation of the crypt-villus axis. The aim is to identify the bacterial components and the signalling cascades involved in establishing the homeostasis of this microbe-host balance, and to analyse how it is disrupted by bacterial pathogens.
CURRICULUM VITAE
SANSONETTI Philippe, Joseph
9 April 1949
French
Current employment
Professeur, Chaire de Microbiologie et Maladies Infectieuses, Collège de France
Professeur, Institut Pasteur
Head Unité de Pathogénie Microbienne Moléculaire and Unité INSERM 786, Institut Pasteur
Education
- MD, Faculté de Médecine, Paris (1979).
- MS, Biochemistry/Microbiology, Faculté des Sciences, Paris 7 (1976)
- Post-doc at Walter Reed Army Institute of Research (Washington DC, USA)
Residencies and medical duties
- Interne des Hôpitaux de Paris
- Chef de Clinique-Assistant des Hôpitaux de Paris
- Head, Out-patient Clinic, Institut Pasteur (1985-1995)
- Medical Director Institut Pasteur (1995-2000)
Principal Honors, Awards.
Prix Jacques Monod (1983)
EMBO member (1993)
Louis-Jeantet Prize of Medicine (Switzerland, 1994)
American Academy of Microbiology (1994)
Robert Koch Prize (Germany, 1997)
AGF-Athena Prize (2000)
André Lwoff Medal (FEMS, 2000)
Howard Hughes Medical Institute Foreign Scholar (2000-2005, renewed 2005-2010)
French Academy of Sciences (2001)
Deutsche Akademie der Natursforscher Leopoldina (2002)
American Association for the Advancement of Science (2006)
External member of the Max Planck Society (2007)
Member of the Swedish Academy for Science and Technology (2008)
European Research Council (ERC) Advanced Grant, HOMEOEPITH (2009-2013)
GlaxoSmithKline International Member of the Year Award (American Society for Microbiology, 2009)
STOPENTERICS, EU/FP7-funded program for vaccination against Shigella and ETEC, Coordinator (2010-2015)
Laboratory of Excellence (Integrative Biology of Emerging Infectious Diseases)
Co-Coordinator with Pascale Cossart (Investment for the future program of the French Government, 2011-2021)
Edition of scientific Journals:
Editor, Infection & Immunity (1992-1998)
Editor Cellular Microbiology (1999-…)
Senior Editor, EMBO Molecular Medicine (2008-...)
Direction of Thesis students and post-docs
Direction of 12 Medical Thesis
Direction of 20 Scientific (Ph.D.) Thesis
Direction of 37 foreign post-docs plus 8 presently in the Laboratory
Publications (ISI, June 29, 2011)
468 publications in international journals
65 articles cited > 100x
7articles cited > 400x
22,466 citations
current h-index = 83
Top ten publications in last ten years (Citation index from ISI Web of Knowledge, March 09, 2009).
Marteyn, B., West, N.P., Browning, D.F., Cole, J.A., Shaw, J.G., Palm, F., Mounier, J., Prévost, M.C., Sansonetti, P.*, Tang, C.M. 2010. The modulation of Shigella virulence in response to available oxygen in vivo.
Nature, 465:355-358 (* corresponding author)
Sperandio, B., Regnault, B., Guo, J., Zhang, Z., Stanley S.L.Jr., Sansonetti, P.J.*, Thierry Pédron. 2008. Virulent Shigella subverts the host innate immune response through manipulation of antimicrobial peptide genes expression. J.Exp.Med., 205:1121-1132. (* corresponding author)
Arbibe, L., Kim, D.W., Batsche, E., Pedron, T., Mateescu, B., Muchardt C., Parsot, C., Sansonetti, P.J. 2007. An injected bacterial effector targets chromatin access for transcription factor NF-kB to alter transcription of host genes involved in immune responses.
Nat. Immunol., 8 :47 – 56 (No. Cited : 79, three editos in Nat.Immunol, Science and Nature).
West, N.P.*, Sansonetti, P*., Mounier, J., Exley, R.M., Parsot, C., Guadagnini, S., Prévost, M-C., Prochnicka-Chalufour, A., Delepierre, M., Tanguy, M., Tang, C.M. 2005. Optimization of Virulence Functions Through Glucosylation of Shigella LPS.
Science, 307 :1313 – 1317 (No cited : 97, one edito in Science, * co-first authors)
Girardin, S.E., Boneca, I.G., Viala, J., Chamaillard, M., Labigne, A., Thomas, G., Philpott, D.J., Sansonetti, P.J. 2003. Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection.
J. Biol. Chem., 278 : 8869-8872 (No cited : 750)
Girardin,S.E., Boneca, I.G., Carneiro, L.A.M., Antignac, A., Jéhanno, M., Viala, J., Tedin, K., Taha, M.K., Labigne, A., Zäthringer, U., Coyle, A.J., DiStefano, P.S., Bertin, J., Sansonetti, P.J., Philpott, D.J. 2003. Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan
Science, 300 :1584 – 1587 (No. Cited : 501)
Girardin, S.E., Tournebize, R., Mavris, M., Page, A.L., Li, X., Stark, G.R., Bertin. J., DiStefano, P.S., Yaniv, M., Sansonetti, P.J., Philpott, D.J. 2001. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri.
EMBO Rep., 2:736-742 (No. Cited : 262)
Sansonetti, P.J., Phalipon, A., Arondel, J., Thirumalai, K., Banerjee, S., Akira, S., Takeda, K., Zychlinsky, A. 2000. Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation.
Immunity., 12:581-590 (No. Cited : 157)
Blocker, A., Gounon, P., Larquet, E., Niebuhr, K., Cabiaux, V., Parsot, C., Sansonetti, P. 1999.
The tripartite type III secreton of Shigella flexneri inserts IpaB and IpaC into host membranes.
J Cell Biol., 147:683-693 (No. Cited : 226)
Tran Van Nhieu, G., Caron, E., Hall, A., Sansonetti, P.J. 1999. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells.
EMBO J., 18:3249-3262 (No. Cited : 111)
Reviews in high-impact journals in last 5 years (mostly in the fields of bacterial invasion of cells and tissues, homeostasis of the gut, and manipulation of innate and adaptive immune responses by pathogens).
Sansonetti P.J., Medzhitov R. 2009. Learning tolerance while fighting ignorance. Cell, 138:416-420
Sansonetti P.J., Di Santo JP. 2007. Debugging how bacteria manipulate the immune response.
Immunity, 26:149-161 (No. cited: 46)
Sansonetti P.J. 2006. The innate signaling of dangers and the dangers of innate signaling.
Nat Immunol., 7:1237-1242 (No. Cited:55)
Cossart, P., Sansonetti, P.J. 2004. Bacterial invasion: the paradigms of enteroinvasive pathogens
Science, 304 :242 – 248 (No.cited : 327)
Sansonetti P.J. 2004. War and peace at mucosal surfaces.
Nat Rev Immunol., 4:953-964 (No
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 | e-mail: | philippe.sansonetti@pasteur.fr | |
 | Phone: | 33(0)145688342 | |
 | Fax: | 33(0)145688953 | |
 | Address: | Institut Pasteur & Collège de France
Institut Pasteur: 28 Rue du Dr Roux
75724 Paris cedex 15, France
Collège de France:
11 Place Marcelin Berthelot
75005 Paris, France
FR - France | |
Last update: Thursday, August 25, 2011
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