{"id":43055,"date":"2021-12-01T11:48:05","date_gmt":"2021-12-01T10:48:05","guid":{"rendered":"https:\/\/www.crct-inserm.fr\/?page_id=43055"},"modified":"2024-01-08T11:59:09","modified_gmt":"2024-01-08T10:59:09","slug":"micropanc_en","status":"publish","type":"page","link":"https:\/\/www.crct-inserm.fr\/en\/micropanc_en\/","title":{"rendered":"MICROPANC_en"},"content":{"rendered":"

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TEAM
Corinne BOUSQUET<\/h1>\n

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MICROPANC<\/strong> :\u00a0<\/h2>\n

Microenvironnement and Therapeutic Resistance
in Pancreatic Neoplasms<\/strong><\/h2>\n

<\/strong><\/p>\n

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Le laboratoire d\u2019Excellence Toulouse Cancer est un projet qui vise \u00e0 comprendre les m\u00e9canismes de r\u00e9sistance et de rechute dans les cancers.<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” use_background_color_gradient=”on” background_color_gradient_stops=”rgba(43,135,218,0) 50%|#f2efef 50%” background_color_gradient_start=”rgba(43,135,218,0)” background_color_gradient_start_position=”50%” background_color_gradient_end=”#f2efef” background_color_gradient_end_position=”0%” custom_padding=”0px|||||” global_colors_info=”{}”][et_pb_row disabled_on=”on|on|on” _builder_version=”4.16″ _module_preset=”default” custom_padding=”0px||0px|||” disabled=”on” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_video src=”https:\/\/www.youtube.com\/watch?v=FkQuawiGWUw” image_src=”https:\/\/www.crct-inserm.fr\/wp-content\/uploads\/2021\/03\/video.jpg” _builder_version=”4.16″ _module_preset=”default” width=”80%” module_alignment=”center” global_colors_info=”{}”][\/et_pb_video][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” background_color=”#f2efef” custom_padding=”0px||0px|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”448e09ae-9652-4ead-bc5f-152c7adf1202″ global_colors_info=”{}”]<\/p>\n

THE SPECIFITIES
<\/strong>OF OUR RESEARCH AXIS<\/h2>\n

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Pancreatic ductal adenocarcinoma (PDAC), commonly known as pancreatic cancer, is a very aggressive tumor since it presents a rapid metastatic potential and a strong therapeutic resistance. This tumor has the particularity of being rich in stroma (up to 80% of its tumor volume), composed of a very fibrotic extracellular matrix, and of immune and non-immune stromal cells, of which cancer-associated fibroblasts (CAFs) are the majority. My research team is specifically interested in the role of CAFs in the aggressiveness of pancreatic cancer cells, with the objective of understanding the biology of CAFs, their dialogues with cancer cells and with other stromal cells (endothelial and immune), and how these dialogues impact the resistance of cancer cells to chemotherapies or immunotherapies. The understanding of these inter-cellular dialogues and with the extracellular matrix allows us to propose and test anti-cancer therapies co-targeting cancer cells and their stroma, in particular by targeted nanotherapies approaches (Veronique Gigoux’s project<\/strong>).<\/o:p><\/span><\/p>\n

Thus, to understand the tumor-stroma dialogues correlated with the aggressiveness of pancreatic cancer, our team is i\/ developing models integrating this stroma and mimicking the pathology in the patient, such as PDX (Patient-Derived Xenografts) and primocultures of CAFs and tumor cells grown in 3 dimensions (tumor organoids) and in co-culture with CAFs, as well as murine pancreatic cancer models (genetically modified mice developing spontaneous cancer, and orthotopic surgical transplantation of pancreatic cancer cells with CAFs) ; and ii\/ performing<\/ins><\/span>s<\/del><\/span> separate analyses of gene expression in the tumor epithelial compartment and in the stromal compartment, using transcriptomics (mRNA expression), translac<\/del><\/span>tomics (translated RNA expression, project of Yvan Martineau<\/strong>), and matrisome (exhaustive analysis of matrix proteins expression, Christine Jean’s project<\/strong>) on PDX (hybrid grafted tumor models) na\u00efve to treatment or rendered chemoresistant (Corinne Bousquet’s project<\/strong>), and\/or by bioinformatics deconvolution on bulk RNAseq of human tumors.<\/ins><\/span><\/o:p><\/span><\/p>\n

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Tumor organoid (left: immunofluorescence to visualize the cytokeratin cytoskeleton in green, the actin filaments particularly abundant at the brush border in pink and the nuclei in blue; right: transmission electron microscopy).<\/span><\/p>\n

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Pancreatic cancer<\/p>\n

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Microenvironment & Cancer-Associated Fibroblasts<\/p>\n

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Metastasis<\/p>\n

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Chemoresistance<\/p>\n

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Translational regulation<\/p>\n

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Metabolic reprogramming<\/p>\n

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Matrix rigidity & mechano-transduction<\/p>\n

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Patient-derived experimental models<\/p>\n

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Targeted nanotherapies<\/p>\n

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(polysome) RNAseq & bioinformatics<\/p>\n

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Matrisome<\/p>\n

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Multiplexed tissue imaging<\/p>\n

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RESEARCH PROJECTS<\/b><\/h2>\n

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THE TEAM’S
<\/strong>FOCUS<\/h2>\n

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Discover<\/h4>\n

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Understand<\/h4>\n

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Participate<\/h4>\n

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En live<\/h2>\n

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\n CRCT-Oncopole<\/span>\n <\/span>\n Suivre<\/span>\n \n <\/path><\/svg>1,220<\/span>\n <\/path><\/svg>1,117<\/span>\n <\/span>\n <\/p>\n

\n Compte officiel du Centre de Recherches en Canc\u00e9rologie de Toulouse <\/p>\n <\/div>\n

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Castelnau-Montratier c\u00e9l\u00e8bre la lutte contre le cancer. Jeudi 24 ao\u00fbt 2023 conf\u00e9rence avec Fr\u00e9d\u00e9ric Chibon responsable de l'\u00e9quipe @OncoSarc du @crctoncopole accompagn\u00e9 de Gwena\u00ebl Ferron et Martin Gauthier oncologue @IUCTOncopole
\nD\u00e9couvrir l'\u00e9quipe
\n\u27a1\ufe0fhttps:\/\/www.crct-inserm.fr\/oncosarc\/ <\/p>\n\t\t\t\t\t\t\n \n

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SCIENTIFIC PRODUCTIONS\u00a0<\/strong><\/h2>\n

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Rapetti-Mauss, Raphael, Jérémy Nigri, Camille Berenguier, Pascal Finetti, Sarah Simha Tubiana, Bonnie Labrum, Benoit Allegrini, et al. “SK2 Channels Set a Signalling Hub Bolstering CAF-Triggered Tumourigenic Processes in Pancreatic Cancer.” Gut<\/i> 72, no. 4 (April 2023): 722–35. https:\/\/doi.org\/10.1136\/gutjnl-2021-326610<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Solorzano, Jacobo, Enrique Carrillo-de Santa Pau, Teresa Laguna, and Ana Busturia. “A Genome-Wide Computational Approach to Define MicroRNA-Polycomb\/Trithorax Gene Regulatory Circuits in Drosophila.” Developmental Biology<\/i> 495 (March 2023): 63–75. https:\/\/doi.org\/10.1016\/j.ydbio.2022.12.008<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Muzzolini, Milena, Ismahane Belhabib, Victoire Cardot, Annemilaï Tijeras-Raballand, Cindy Neuzillet, Corinne Bousquet, Renato Micelli Lupinacci, and Christine Jean. “Pancreatic Cancer Orthotopic Graft in a Murine Model.” Acta Cirurgica Brasileira<\/i> 38 (2023): e382823. https:\/\/doi.org\/10.1590\/acb382823<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

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Neuzillet, Cindy, Rémy Nicolle, Jérôme Raffenne, Annemilaï Tijeras-Raballand, Alexia Brunel, Lucile Astorgues-Xerri, Sophie Vacher, et al. “Periostin- and Podoplanin-Positive Cancer-Associated Fibroblast Subtypes Cooperate to Shape the Inflamed Tumor Microenvironment in Aggressive Pancreatic Adenocarcinoma.” The Journal of Pathology<\/i> 258, no. 4 (December 2022): 408–25. https:\/\/doi.org\/10.1002\/path.6011<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Shin, Sauyeun, Jacobo Solorzano, Mehdi Liauzun, Stéphane Pyronnet, Corinne Bousquet, and Yvan Martineau. “Translational Alterations in Pancreatic Cancer: A Central Role for the Integrated Stress Response.” NAR Cancer<\/i> 4, no. 4 (December 2022): zcac031. https:\/\/doi.org\/10.1093\/narcan\/zcac031<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Sánchez-Morales, Adrià, Véronique Gigoux, Minos-Timotheos Matsoukas, Laura Perez-Benito, Daniel Fourmy, Ramón Alibes, Félix Busqué, Arnau Cordomí, and Jean-Marc Devaud. “Reduction of Stress Responses in Honey Bees by Synthetic Ligands Targeting an Allatostatin Receptor.” Scientific Reports<\/i> 12, no. 1 (October 6, 2022): 16760. https:\/\/doi.org\/10.1038\/s41598-022-20978-y<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Ponzo, Matteo, Anais Debesset, Mélissande Cossutta, Mounira Chalabi-Dchar, Claire Houppe, Caroline Pilon, Alba Nicolas-Boluda, et al. “Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression.” Cancers<\/i> 14, no. 17 (August 31, 2022): 4265. https:\/\/doi.org\/10.3390\/cancers14174265<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

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Hilmi, Marc, Rémy Nicolle, Corinne Bousquet, and Cindy Neuzillet. “Cancer-Associated Fibroblasts: Accomplices in the Tumor Immune Evasion.” Cancers<\/i> 12, no. 10 (October 14, 2020): 2969. https:\/\/doi.org\/10.3390\/cancers12102969<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Zaghdoudi, Sonia, Emilie Decaup, Ismahane Belhabib, Rémi Samain, Stéphanie Cassant‐Sourdy, Julia Rochotte, Alexia Brunel, et al. “Activity in Cancer‐associated Fibroblasts Is a Prognostic Marker and a Druggable Key Metastatic Player in Pancreatic Cancer.” EMBO Molecular Medicine<\/i>, October 7, 2020. https:\/\/doi.org\/10.15252\/emmm.202012010<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

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%20but%20how%20their%20respective%20intracellular%20amounts%20are%20controlled%20remains%20poorly%20understood.%20Here%20we%20show%20that%20eIF4GI%20and%20eIF4GII%20exhibit%20much%20shorter%20half-lives%20than%20that%20of%20DAP5.%20Both%20eIF4GI%20and%20eIF4GII%20proteins%2C%20but%20not%20DAP5%2C%20contain%20computer-predicted%20PEST%20motifs%20in%20their%20N-termini%20conserved%20across%20the%20animal%20kingdom.%20They%20are%20both%20sensitive%20to%20degradation%20by%20the%20proteasome.%20Under%20normal%20conditions%2C%20eIF4GI%20and%20eIF4GII%20are%20protected%20from%20proteasomal%20destruction%20through%20binding%20to%20the%20detoxifying%20enzyme%20NQO1%20%5BNAD%28P%29H%3Aquinone%20oxidoreductase%5D.%20However%2C%20when%20cells%20are%20exposed%20to%20oxidative%20stress%20both%20eIF4GI%20and%20eIF4GII%2C%20but%20not%20DAP5%2C%20are%20degraded%20by%20the%20proteasome%20in%20an%20N-terminal-dependent%20manner%2C%20and%20cell%20viability%20is%20more%20compromised%20upon%20silencing%20of%20DAP5.%20These%20findings%20indicate%20that%20the%20three%20eIF4G%20proteins%20are%20differentially%20regulated%20by%20the%20proteasome%20and%20that%20persistent%20DAP5%20plays%20a%20role%20in%20cell%20survival%20upon%20oxidative%20stress.%22%2C%22date%22%3A%222019%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.3389%5C%2Ffgene.2019.00254%22%2C%22ISSN%22%3A%221664-8021%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22NPEV4ECN%22%2C%22VDZ48X5N%22%5D%2C%22dateModified%22%3A%222021-04-26T15%3A23%3A10Z%22%7D%7D%5D%7D<\/span>\n\n\t\t\t\t
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Müller, David, Sauyeun Shin, Théo Goullet de Rugy, Rémi Samain, Romain Baer, Manon Strehaiano, Laia Masvidal-Sanz, et al. “EIF4A Inhibition Circumvents Uncontrolled DNA Replication Mediated by 4E-BP1 Loss in Pancreatic Cancer.” JCI Insight<\/i> 4, no. 21 (November 1, 2019). https:\/\/doi.org\/10.1172\/jci.insight.121951<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Laplagne, Chloé, Marcin Domagala, Augustin Le Naour, Christophe Quemerais, Dimitri Hamel, Jean-Jacques Fournié, Bettina Couderc, Corinne Bousquet, Audrey Ferrand, and Mary Poupot. “Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression.” International Journal of Molecular Sciences<\/i> 20, no. 19 (September 23, 2019). https:\/\/doi.org\/10.3390\/ijms20194719<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Saponaro, Chiara, Valéry Gmyr, Julien Thévenet, Ericka Moerman, Nathalie Delalleau, Gianni Pasquetti, Anais Coddeville, et al. “The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release.” Cell Reports<\/i> 28, no. 6 (August 6, 2019): 1447-1454.e4. https:\/\/doi.org\/10.1016\/j.celrep.2019.07.009<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Neuzillet, Cindy, Annemilaï Tijeras-Raballand, Chanthirika Ragulan, Jérôme Cros, Yatish Patil, Matthieu Martinet, Mert Erkan, et al. “Inter- and Intra-Tumoural Heterogeneity in Cancer-Associated Fibroblasts of Human Pancreatic Ductal Adenocarcinoma.” The Journal of Pathology<\/i> 248, no. 1 (May 2019): 51–65. https:\/\/doi.org\/10.1002\/path.5224<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Goehrig, Delphine, Jérémy Nigri, Rémi Samain, Zhichong Wu, Paola Cappello, Gaëlle Gabiane, Xinyi Zhang, et al. “Stromal Protein Βig-H3 Reprogrammes Tumour Microenvironment in Pancreatic Cancer.” Gut<\/i> 68, no. 4 (2019): 693–707. https:\/\/doi.org\/10.1136\/gutjnl-2018-317570<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Alard, Amandine, Catherine Marboeuf, Bertrand Fabre, Christine Jean, Yvan Martineau, Frédéric Lopez, Patrice Vende, et al. “Differential Regulation of the Three Eukaryotic MRNA Translation Initiation Factor (EIF) 4Gs by the Proteasome.” Frontiers in Genetics<\/i> 10 (2019): 254. https:\/\/doi.org\/10.3389\/fgene.2019.00254<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

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team members<\/strong><\/h2>\n

[\/et_pb_text][et_pb_divider color=”#F19532″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” max_width=”none” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

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\"\"<\/a><\/div>\n
Pauline Thomas<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Charline Ogier<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Maxime Boyer<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Ossama Kohil<\/a><\/div>\n
Master \/ Master student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
C\u00e9dric Fabre<\/a><\/div>\n
Master \/ Master student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Morgane Le Bras<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Petnoi Petsophonsakul<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Evangelia Papadopoulou<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Ludmila Recoules<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Delphine Vezzosi<\/a><\/div>\n
Hospitalo-Universitaire \/ University teacher hospital practitioner<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\n
\"\"<\/a><\/div>\n
Pascal Clerc<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Mehdi Liauzun<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\n
\"\"<\/a><\/div>\n
Marjorie Fanjul<\/a><\/div>\n
Enseignant chercheur \/ University researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
\n
\n
\"\"<\/a><\/div>\n
Jacobo Solorzano<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\n
\"\"<\/a><\/div>\n
Veronique Gigoux<\/a><\/div>\n
Chercheur statutaire \/ permanent scientist<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
\n
\n
\"\"<\/a><\/div>\n
Ahmed Abdelhamid<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\n
\"\"<\/a><\/div>\n
Hippolyte Audureau<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\n
\"\"<\/a><\/div>\n
Justine Journaux<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
\n
\n
\"\"<\/a><\/div>\n
Loubna Laib<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
\n
\n
\"\"<\/a><\/div>\n
Corinne Bousquet<\/a><\/div>\n
Chercheur statutaire \/ permanent scientist<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n <\/div>\n<\/div><\/div>\n\n