Équipe
STÉPHANE PYRONNET & FABIENNE MEGGETTO

R’n Blood :

Biologie des ARN dans les Tumeurs Hématologiques

 

Le laboratoire d’Excellence Toulouse Cancer est un projet qui vise à comprendre les mécanismes de résistance et de rechute dans les cancers.

Les spécificités
de notre axe de recherche

Les événements post-transcriptionnels touchant les ARN permettent de contrôler l’expression génique rapidement et à moindre cout énergétique pour la cellule. Ils sont particulièrement sollicités lorsque les cellules sont soumises à un environnement stressé, comme dans une tumeur maligne ou sous l’effet de traitements anti-tumoraux. Ils peuvent alors contribuer aux processus d’adaptation nécessaires à la transformation maligne et/ou à la résistance aux traitements.

Dans une perspective clinique, par des approches combinées de séquençage nouvelle génération et haut débit des ARN (« bulk » ou « single-cell RNAseq ») et d’imagerie cellulaire et tissulaire, notre équipe explore l’ensemble du répertoire des ARN (ARNm codants et ARN régulateurs non codants incluant les miRNAs, lncRNAs et circRNAs) et son hétérogénéité au sein de la tumeur, dans les cohortes de patients atteints de tumeurs hématologiques (leucémies aiguës et lymphomes anaplasiques). L’objectif est l’identification de nouvelles cibles thérapeutiques et/ou de sensibilisation aux traitements existants.

Sur un plan cognitif et mécanistique, l’équipe met ensuite en œuvre les approches expérimentales moléculaires (gain/perte de fonction), cellulaires et in vivo (modèles génétiques et avatars de tumeurs humaines ou PDX) permettant à la fois la caractérisation fonctionnelle des cibles potentielles et la description de leurs mécanismes d’action. En partenariat avec des industriels, la possibilité de les cibler par des molécules à potentiel thérapeutique est également explorée.

Traduction des ARNm

ARN non codants

miARN

lncARN

circARN

Stress du réticulum

Leucémie aiguë

Lymphome T pédiatrique

Oncogenèse

Résistance aux traitements

Thérapies ciblées

Biomarqueurs

DES PROJETS
DE RECHERCHE

LES FOCUS
DE L’ÉQUIPE

Découvrir

Transipedia : projet pour l’exploration de séquences à grande échelle et application pour le cancer

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Seconde saison des Apprentis Chercheurs au CRCT

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Focus recherche 2022 équipe R’nBlood

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Fabienne Meggetto primée par le Fonds Amgen France

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La Fondation Roland Garigou pour la Culture & la santé attribue plusieurs prix et bourses au CRCT en 2022

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Comprendre

Les ARN non codant contre la résistance aux traitements des lymphômes T pédiatriques

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Septembre en Or, mois international des cancers de l’enfant

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10 ans de recherche contre le Cancer : Toulouse au cœur de la lutte

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La cellule tumorale

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L’immunothérapie en cancérologie

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Participer

TOW2025 J-30 inscription anticipée

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L’association Cassandra accompagne un chercheur du CRCT

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Labellisation du groupe de Fabienne Megetto par la Fondation pour la Recherche Médicale pendant 3 ans

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Le Lion’s Club de Lourdes encourage la recherche au CRCT

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En live

RnBlood_CRCT Suivre 142 91

Official account of the research group "RNA Biology in Hematologic Tumors" at the Cancer Research Center of Toulouse @crctoncopole #noncodingRNA #hematology

RnbloodC
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PRODUCTIONS SCIENTIFIQUES

PUBLICATIONS 2024
Bessière, Chloé, Haoliang Xue, Benoit Guibert, Anthony Boureux, Florence Rufflé, Julien Viot, Rayan Chikhi, et al. “Transipedia.Org: K-Mer-Based Exploration of Large RNA Sequencing Datasets and Application to Cancer Data.” Genome Biology 25, no. 1 (October 10, 2024): 266. https://doi.org/10.1186/s13059-024-03413-5.
Philippe, Céline, Manon Jaud, Kelly Féral, Alexandre Gay, Loïc Van Den Berghe, Manon Farce, Marina Bousquet, et al. “Pivotal Role of the Endoplasmic Reticulum Stress-Related XBP1s/MiR-22/SIRT1 Axis in Acute Myeloid Leukemia Apoptosis and Response to Chemotherapy.” Leukemia, June 22, 2024. https://doi.org/10.1038/s41375-024-02321-8.
Corre, Eulalie, Cécile Soum, Romain Pfeifer, Chloé Bessière, Sandra Dailhau, Catherine Marbœuf, Fabienne Meggetto, et al. “Differential Prognostic Values of the Three AKT Isoforms in Acute Myeloid Leukemia.” Scientific Reports 14, no. 1 (March 25, 2024): 7070. https://doi.org/10.1038/s41598-024-57578-x.
PUBLICATIONS 2023
Cortacero, Kévin, Brienne McKenzie, Sabina Müller, Roxana Khazen, Fanny Lafouresse, Gaëlle Corsaut, Nathalie Van Acker, et al. “Evolutionary Design of Explainable Algorithms for Biomedical Image Segmentation.” Nature Communications 14, no. 1 (November 6, 2023): 7112. https://doi.org/10.1038/s41467-023-42664-x.
Brugières, Laurence, Nathalie Cozic, Roch Houot, Charlotte Rigaud, David Sibon, Julia Arfi-Rouche, Pierre Bories, et al. “Efficacy and Safety of Crizotinib in ALK-Positive Systemic Anaplastic Large-Cell Lymphoma in Children, Adolescents, and Adult Patients: Results of the French AcSé-Crizotinib Trial.” European Journal of Cancer (Oxford, England: 1990) 191 (July 17, 2023): 112984. https://doi.org/10.1016/j.ejca.2023.112984.
Legrand, Mélanie, Daniel Pissaloux, Franck Tirode, Anne Tallet, Christine Collin, Paul-Louis Chantreau, Patricia Berthon, et al. “SSTR2A Is a Diagnostic Marker of Trichogerminoma.” Journal of the European Academy of Dermatology and Venereology: JEADV, July 8, 2023. https://doi.org/10.1111/jdv.19319.
Fuchs, Steffen, Clara Danßmann, Filippos Klironomos, Annika Winkler, Jörg Fallmann, Louisa-Marie Kruetzfeldt, Annabell Szymansky, et al. “Defining the Landscape of Circular RNAs in Neuroblastoma Unveils a Global Suppressive Function of MYCN.” Nature Communications 14, no. 1 (July 4, 2023): 3936. https://doi.org/10.1038/s41467-023-38747-4.
Scholaert, Manon, Raissa Houmadi, Jeremy Martin, Nadine Serhan, Marie Tauber, Emilie Braun, Lilian Basso, et al. “3D Deconvolution of Human Skin Immune Architecture with Multiplex Annotated Tissue Imaging System.” Science Advances 9, no. 23 (June 9, 2023): eadf9491. https://doi.org/10.1126/sciadv.adf9491.
Beishuizen, Auke, Karin Mellgren, Mara Andrés, Anne Auperin, Chris M. Bacon, Simon Bomken, G. A. Amos Burke, et al. “Improving Outcomes of Childhood and Young Adult Non-Hodgkin Lymphoma: 25 Years of Research and Collaboration within the Framework of the European Intergroup for Childhood Non-Hodgkin Lymphoma.” The Lancet. Haematology 10, no. 3 (March 2023): e213–24. https://doi.org/10.1016/S2352-3026(22)00374-X.
Troadec, Marie-Bérengère, Françoise Porteu, Marie-Laure Arcangeli, Adlen Foudi, Dominique Bluteau, Paulo De Sepulveda, Christel Guillouf, et al. “From Normal Hematopoiesis to Malignancies: Highlights from the 2021 Meeting of the Club Hematopoiesis and Oncogenesis.” Bulletin Du Cancer 110, no. 3 (March 2023): 331–35. https://doi.org/10.1016/j.bulcan.2022.12.013.
PUBLICATIONS 2022
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 4, no. 4 (December 2022): zcac031. https://doi.org/10.1093/narcan/zcac031.
Carrier, Arnaud, Cécile Desjobert, Valérie Lobjois, Lise Rigal, Florence Busato, Jörg Tost, Miquel Ensenyat-Mendez, et al. “Epigenetically Regulated PCDHB15 Impairs Aggressiveness of Metastatic Melanoma Cells.” Clinical Epigenetics 14, no. 1 (November 28, 2022): 156. https://doi.org/10.1186/s13148-022-01364-x.
Carrier, Arnaud, Cécile Desjobert, Loic Ponger, Laurence Lamant, Matias Bustos, Jorge Torres-Ferreira, Rui Henrique, et al. “DNA Methylome Combined with Chromosome Cluster-Oriented Analysis Provides an Early Signature for Cutaneous Melanoma Aggressiveness.” ELife 11 (September 20, 2022): e78587. https://doi.org/10.7554/eLife.78587.
Fuchs, Steffen, Loélia Babin, Elissa Andraos, Chloé Bessiere, Semjon Willier, Johannes H. Schulte, Christine Gaspin, and Fabienne Meggetto. “Generation of Full-Length Circular RNA Libraries for Oxford Nanopore Long-Read Sequencing.” PloS One 17, no. 9 (September 7, 2022): e0273253. https://doi.org/10.1371/journal.pone.0273253.
Soulages, Antoine, Thierry Maisonobe, Pascal Auzou, Antoine Petit, Yves Allenbach, Stéphane Barète, Sophie Skopinski, et al. “Peripheral Neuropathy and Livedoid Vasculopathy.” Journal of Neurology 269, no. 7 (July 2022): 3779–88. https://doi.org/10.1007/s00415-022-11007-z.
Darmon-Novello, Marie, Julien Adam, Laurence Lamant, Maxime Battistella, Nicolas Ortonne, Brigitte Balme, A. de la Fouchardière, et al. “Harmonization of Programmed Death-Ligand 1 Immunohistochemistry and MRNA Expression Scoring in Metastatic Melanoma: A Multicentre Analysis.” Histopathology 80, no. 7 (June 2022): 1091–1101. https://doi.org/10.1111/his.14651.
Kervarrec, Thibault, Daniel Pissaloux, Jeremie Poilane, Franck Tirode, Anne Tallet, Christine Collin, Matthias Tallegas, et al. “Recurrent FOXK1::GRHL and GPS2::GRHL Fusions in Trichogerminoma.” The Journal of Pathology 257, no. 1 (May 2022): 96–108. https://doi.org/10.1002/path.5872.
Vergnolle, Inès, Claudia Douat-Beyries, Serge Boulinguez, Jean-Baptiste Rieu, Jean-Philippe Vial, Rolande Baracou, Sylvie Boudot, et al. “CD158k and PD-1 Expressions Define Heterogeneous Subtypes of Sezary Syndrome.” Blood Advances 6, no. 6 (March 22, 2022): 1813–25. https://doi.org/10.1182/bloodadvances.2021005147.
Babin, Loélia, Alice Darchen, Elie Robert, Zakia Aid, Rosalie Borry, Claire Soudais, Marion Piganeau, et al. “De Novo Generation of the NPM-ALK Fusion Recapitulates the Pleiotropic Phenotypes of ALK+ ALCL Pathogenesis and Reveals the ROR2 Receptor as Target for Tumor Cells.” Molecular Cancer 21, no. 1 (March 4, 2022): 65. https://doi.org/10.1186/s12943-022-01520-0.
Battistella, Maxime, Brigitte Balme, Marie-Laure Jullie, Ute Zimmermann, Agnès Carlotti, Marie Crinquette, Eric Frouin, et al. “Impact of Expert Pathology Review in Skin Adnexal Carcinoma Diagnosis: Analysis of 2573 Patients from the French CARADERM Network.” European Journal of Cancer (Oxford, England: 1990) 163 (March 2022): 211–21. https://doi.org/10.1016/j.ejca.2021.11.027.
Filali, Liza, Marie-Pierre Puissegur, Kevin Cortacero, Sylvain Cussat-Blanc, Roxana Khazen, Nathalie Van Acker, François-Xavier Frenois, et al. “Ultrarapid Lytic Granule Release from CTLs Activates Ca2+-Dependent Synaptic Resistance Pathways in Melanoma Cells.” Science Advances 8, no. 7 (February 18, 2022): eabk3234. https://doi.org/10.1126/sciadv.abk3234.
PUBLICATIONS 2021
Babin, Loelia, Elissa Andraos, Steffen Fuchs, Stéphane Pyronnet, Erika Brunet, and Fabienne Meggetto. “From CircRNAs to Fusion CircRNAs in Hematological Malignancies.” JCI Insight 6, no. 21 (November 8, 2021): e151513. https://doi.org/10.1172/jci.insight.151513.
Camille, Daugrois, Bessiere Chloé, Dejean Sébastien, Anton Leberre Véronique, Commes Thérèse, Stephane Pyronnet, Pierre Brousset, et al. “Gene Expression Signature Associated with Clinical Outcome in ALK-Positive Anaplastic Large Cell Lymphoma.” Cancers 13, no. 21 (November 3, 2021): 5523. https://doi.org/10.3390/cancers13215523.
Gourvest, Morgane, Etienne De Clara, Hsin-Chieh Wu, Christian Touriol, Fabienne Meggetto, Hugues De Thé, Stéphane Pyronnet, Pierre Brousset, and Marina Bousquet. “A Novel Leukemic Route of Mutant NPM1 through Nuclear Import of the Overexpressed Long Noncoding RNA LONA.” Leukemia 35, no. 10 (October 2021): 2784–98. https://doi.org/10.1038/s41375-021-01307-0.
Alard, Amandine, Manon Strehaïano, David Müller, Charline Lasfargues, Stéphanie Cassant-Sourdy, Christine Jean, Corinne Bousquet, Yvan Martineau, and Stéphane Pyronnet. “Phosphorylation of the MNK1 Substrate EIF4E Is Not Required for Response to Acute Pancreatitis.” Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.] 21, no. 4 (June 2021): 677–81. https://doi.org/10.1016/j.pan.2021.02.013.
Syrykh, Charlotte, Loïc Ysebaert, Sarah Péricart, Solène M. Evrard, Fabienne Meggetto, Salim Kanoun, Pierre Brousset, and Camille Laurent. “ALK-Positive Histiocytosis Associated with Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma: A Multitarget Response under Ibrutinib.” Virchows Archiv: An International Journal of Pathology 478, no. 4 (April 2021): 779–83. https://doi.org/10.1007/s00428-020-02937-y.
Féral, Kelly, Manon Jaud, Céline Philippe, Doriana Di Bella, Stéphane Pyronnet, Kevin Rouault-Pierre, Laurent Mazzolini, and Christian Touriol. “ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?” Biomolecules 11, no. 2 (January 30, 2021). https://doi.org/10.3390/biom11020199.
Andraos, Elissa, Joséphine Dignac, and Fabienne Meggetto. “NPM-ALK: A Driver of Lymphoma Pathogenesis and a Therapeutic Target.” Cancers 13, no. 1 (January 5, 2021). https://doi.org/10.3390/cancers13010144.
Samain, Rémi, Alexia Brunel, Thibault Douché, Marjorie Fanjul, Stéphanie Cassant-Sourdy, Julia Rochotte, Jérôme Cros, et al. “Pharmacologic Normalization of Pancreatic Cancer-Associated Fibroblast Secretome Impairs Prometastatic Cross-Talk With Macrophages.” Cellular and Molecular Gastroenterology and Hepatology 11, no. 5 (2021): 1405–36. https://doi.org/10.1016/j.jcmgh.2021.01.008.
PUBLICATIONS 2020
Congras, Annabelle, Coralie Hoareau-Aveilla, Nina Caillet, Marie Tosolini, Patrick Villarese, Agata Cieslak, Laura Rodriguez, et al. “ALK-Transformed Mature T Lymphocytes Restore Early Thymus Progenitor Features.” Journal of Clinical Investigation, November 3, 2020, 10.1172/JCI134990. https://doi.org/10.1172/JCI134990.
Sorrentino, Domenico, Julie Frentzel, Géraldine Mitou, Rafael B. Blasco, Avédis Torossian, Coralie Hoareau-Aveilla, Chiara Pighi, et al. “High Levels of MiR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells.” Cancers 12, no. 10 (October 13, 2020): 2951. https://doi.org/10.3390/cancers12102951.
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, October 7, 2020. https://doi.org/10.15252/emmm.202012010.
Jaud, Manon, Céline Philippe, Doriana Di Bella, Weiwei Tang, Stéphane Pyronnet, Henrik Laurell, Laurent Mazzolini, Kevin Rouault-Pierre, and Christian Touriol. “Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers.” Cells 9, no. 3 (February 26, 2020): 540. https://doi.org/10.3390/cells9030540.
PUBLICATIONS 2019
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 4, no. 21 (November 1, 2019). https://doi.org/10.1172/jci.insight.121951.
Fuchs, Steffen, Julian Naderi, and Fabienne Meggetto. “Non-Coding RNA Networks in ALK-Positive Anaplastic-Large Cell Lymphoma.” International Journal of Molecular Sciences 20, no. 9 (April 30, 2019). https://doi.org/10.3390/ijms20092150.
Hoareau-Aveilla, Coralie, Cathy Quelen, Annabelle Congras, Nina Caillet, Delphine Labourdette, Christine Dozier, Pierre Brousset, Laurence Lamant, and Fabienne Meggetto. “MiR-497 Suppresses Cycle Progression through an Axis Involving CDK6 in ALK-Positive Cells.” Haematologica 104, no. 2 (February 2019): 347–59. https://doi.org/10.3324/haematol.2018.195131.
Jaud, Manon, Céline Philippe, Loic Van Den Berghe, Christèle Ségura, Laurent Mazzolini, Stéphane Pyronnet, Henrik Laurell, and Christian Touriol. “The PERK Branch of the Unfolded Protein Response Promotes DLL4 Expression by Activating an Alternative Translation Mechanism.” Cancers 11, no. 2 (January 25, 2019). https://doi.org/10.3390/cancers11020142.
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 10 (2019): 254. https://doi.org/10.3389/fgene.2019.00254.

LES MEMBRES DE L’ÉQUIPE

Lola Colras
Ingénieur de laboratoire / laboratory engineer
Guillaume Flandin
Master / Master student
Sandra Dailhau
Ingénieur de laboratoire / laboratory engineer
Laurent Mazzolini
Chercheur statutaire / permanent scientist
Ahmed Zamani
Doctorant / PhD student
Chloé Bessiere
Chercheur Post-Doctorant / Post-Doc researcher
Christian Touriol
Chercheur statutaire / permanent scientist
Laurence Lamant
Enseignant chercheur / University researcher
Stéphane Pyronnet
Chercheur statutaire / permanent scientist
Fabienne Meggetto
Chercheur statutaire / permanent scientist
Alexandre Gay
Ingénieur de laboratoire / laboratory engineer
Catherine Marboeuf
Technicien de laboratoire / Laboratory Technician
Eulalie Corre
Doctorant / PhD student
Elissa Andraos
Doctorant / PhD student
Cécile Soum
Doctorant / PhD student
Romain Pfeifer
Doctorant / PhD student
Marina Bousquet
Chercheur statutaire / permanent scientist
Steffen Fuchs
Chercheur Post-Doctorant / Post-Doc researcher
Loélia Babin
Chercheur Post-Doctorant / Post-Doc researcher

LES PARTENAIRES & FINANCIERS

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches contre le Cancer de Toulouse (Oncopole)

Toulouse - FR

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+33 5 82 74 15 75

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