Équipe
Bruno ségui – nathalie andrieu

MELASPHINX :

Métabolisme du céramide dans le mélanome : des mécanismes moléculaires à l’immunothérapie

Présentation générale de l’équipe 

Notre équipe a été créée en 2011, sous la direction du Pr. Thierry Levade. Depuis 2021, elle est dirigée par le Pr. Bruno Ségui et le Dr. Nathalie Andrieu-Abadie. Elle est composée de 26 membres, incluant 3 chercheurs/6 enseignants-chercheurs, 5 ingénieurs/techniciens, 2 praticiens hospitaliers, 2 post-doctorants, 5 doctorants et 3 stagiaires de master par an.

Objectifs scientifiques

Le mélanome cutané représente la principale cause de décès parmi les cancers de la peau. Les inhibiteurs de points de contrôle immunitaire (ICI) ont révolutionné la prise en charge thérapeutique des patients atteints du mélanome cutané avancé. Toutefois, seule la moitié des patients répond de façon durable aux ICI en raison de mécanismes de résistance primaires ou adaptatifs. Des profils lipidiques anormaux sont souvent associés à un phénotype métabolique altéré dans les cellules tumorales, qui est une caractéristique du cancer. L’activité scientifique de notre équipe vise à mieux comprendre les mécanismes moléculaires par lesquels les altérations du métabolisme du céramide contribuent à la progression du mélanome, à l’échappement immunitaire et à la résistance aux ICI dans des modèles précliniques de mélanome. Grâce aux collaborations existantes entre les chercheurs et les cliniciens, notre ambition est de transférer nos découvertes scientifiques fondamentales à la clinique dans le but d’identifier de nouveaux biomarqueurs permettant de prédire la réponse aux ICI et de proposer des traitements adaptés aux patients atteints de mélanome avancé. En outre, nos travaux de recherche, réalisés au cours des 5 dernières années, ont constitué le rationnel scientifique de trois essais cliniques chez 150 patients atteints de mélanome avancé, traités par immunothérapie. Ces essais sont sous la responsabilité du Pr. Nicolas Meyer, oncodermatologue à l’IUCT.

Notre objectif ultime est de reprogrammer le métabolisme du céramide pour améliorer l’efficacité thérapeutique.

Les spécificités

de notre axe de recherche

Mélanome

Métabolisme

Céramide

Immunothérapie

TNF

DES PROJETS
DE RECHERCHE

LES FOCUS
DE L’ÉQUIPE

Découvrir

Seconde saison des Apprentis Chercheurs au CRCT

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Défauts génétiques humains de la synthèse des sphingolipides

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Etude de la contribution de lipides tumoraux dans l’évolution métastatique d’un mélanome cutané

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Focus recherche 2022 équipe MELASPHINX

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Vers une nouvelle approche de l’immunothérapie dans le traitement des cancers de la peau

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Comprendre

Un vaccin contre le cancer

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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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En live

MELASPHINX Suivre 174 165

Research team at the Cancer Research Center of Toulouse (France) on ceramide metabolism in melanoma: from basic mechanisms to the clinic.

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PRODUCTIONS SCIENTIFIQUES

PUBLICATIONS 2024
Combarel, David, Léa Dousset, Stéphane Bouchet, Florent Ferrer, Pauline Tetu, Céleste Lebbe, Joseph Ciccolini, Nicolas Meyer, and Angelo Paci. “Tyrosine Kinase Inhibitors in Cancers: Treatment Optimization - Part I.” Critical Reviews in Oncology/Hematology, May 16, 2024, 104384. https://doi.org/10.1016/j.critrevonc.2024.104384.
Dubot, Patricia, Frédérique Sabourdy, and Thierry Levade. “Human Genetic Defects of Sphingolipid Synthesis.” Journal of Inherited Metabolic Disease, May 5, 2024. https://doi.org/10.1002/jimd.12745.
Borie-Guichot, Marc, My Lan Tran, Virginie Garcia, Abdelouahd Oukhrib, Frédéric Rodriguez, Cédric-Olivier Turrin, Thierry Levade, Yves Génisson, Stéphanie Ballereau, and Cécile Dehoux. “Multivalent Pyrrolidines Acting as Pharmacological Chaperones against Gaucher Disease.” Bioorganic Chemistry 146 (March 16, 2024): 107295. https://doi.org/10.1016/j.bioorg.2024.107295.
Casasampere, Mireia, Johnson Ung, Alejandro Iñáñez, Carine Duffau, Kazuhito Tsuboi, Josefina Casas, Su-Fern Tan, et al. “A Fluorogenic Substrate for the Detection of Lipid Amidases in Intact Cells.” Journal of Lipid Research, February 16, 2024, 100520. https://doi.org/10.1016/j.jlr.2024.100520.
Krug, Adrien, Marie Tosolini, Blandine Madji Hounoum, Jean-Jacques Fournié, Roger Geiger, Matteo Pecoraro, Patrick Emond, et al. “Inhibition of Choline Metabolism in an Angioimmunoblastic T-Cell Lymphoma Preclinical Model Reveals a New Metabolic Vulnerability as Possible Target for Treatment.” Journal of Experimental & Clinical Cancer Research: CR 43, no. 1 (February 6, 2024): 43. https://doi.org/10.1186/s13046-024-02952-w.
Rives, Clémence, Céline Marie Pauline Martin, Lauris Evariste, Arnaud Polizzi, Marine Huillet, Frédéric Lasserre, Valérie Alquier-Bacquie, et al. “Dietary Amino Acid Source Elicits Sex-Specific Metabolic Response to Diet-Induced NAFLD in Mice.” Molecular Nutrition & Food Research 68, no. 1 (January 2024): e2300491. https://doi.org/10.1002/mnfr.202300491.
Dufau, Carine, Matthieu Genais, Elodie Mucher, Benjamin Jung, Virginie Garcia, Anne Montfort, Marie Tosolini, et al. “Ceramide Metabolism Alterations Contribute to Tumor Necrosis Factor-Induced Melanoma Dedifferentiation and Predict Resistance to Immune Checkpoint Inhibitors in Advanced Melanoma Patients.” Frontiers in Immunology 15 (2024): 1421432. https://doi.org/10.3389/fimmu.2024.1421432.
PUBLICATIONS 2023
Noujarède, Justine, Lorry Carrié, Virginie Garcia, Maxime Grimont, Anaïs Eberhardt, Elodie Mucher, Matthieu Genais, et al. “Sphingolipid Paracrine Signaling Impairs Keratinocyte Adhesion to Promote Melanoma Invasion.” Cell Reports 42, no. 12 (December 18, 2023): 113586. https://doi.org/10.1016/j.celrep.2023.113586.
Tran, My Lan, Marc Borie-Guichot, Virginie Garcia, Abdelouahd Oukhrib, Yves Génisson, Thierry Levade, Stéphanie Ballereau, Cédric-Olivier Turrin, and Cécile Dehoux. “Phosphorus Dendrimers for Metal-Free Ligation: Design of Multivalent Pharmacological Chaperones against Gaucher Disease.” Chemistry (Weinheim an Der Bergstrasse, Germany) 29, no. 53 (September 21, 2023): e202301210. https://doi.org/10.1002/chem.202301210.
Kleynerman, Annie, Jitka Rybova, Mary L. Faber, William M. McKillop, Thierry Levade, and Jeffrey A. Medin. “Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions.” Biomolecules 13, no. 2 (February 1, 2023): 274. https://doi.org/10.3390/biom13020274.
PUBLICATIONS 2022
Corrie, Pippa, Nicolas Meyer, Rossana Berardi, Massimo Guidoboni, Maximilian Schlueter, Spyros Kolovos, Bérengère Macabeo, Jean-Baptiste Trouiller, and Philippe Laramée. “Erratum to ‘Comparative Efficacy and Safety of Targeted Therapies for BRAF-Mutant Unresectable or Metastatic Melanoma: Results from a Systematic Literature Review and a Network Meta-Analysis’ [Cancer Treat. Rev. 110 (2022) 102463].” Cancer Treatment Reviews 112 (December 8, 2022): 102495. https://doi.org/10.1016/j.ctrv.2022.102495.
Lee, Michelle M., Graeme S. V. McDowell, Darryl C. De Vivo, Daniel Friedman, Samuel F. Berkovic, Maria Spanou, Argirios Dinopoulos, et al. “The Clinical Spectrum of SMA-PME and in Vitro Normalization of Its Cellular Ceramide Profile.” Annals of Clinical and Translational Neurology 9, no. 12 (December 2022): 1941–52. https://doi.org/10.1002/acn3.51687.
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.
Corrie, Pippa, Nicolas Meyer, Rossana Berardi, Massimo Guidoboni, Max Schlueter, Spyros Kolovos, Bérengère Macabeo, Jean-Baptiste Trouiller, and Philippe Laramée. “Response to ‘Considerations Regarding a Network Meta-Analysis of Targeted Therapies for BRAF Mutant Unresectable or Metastatic Melanoma.’” Cancer Treatment Reviews 111 (October 22, 2022): 102478. https://doi.org/10.1016/j.ctrv.2022.102478.
Dubot, Patricia, Leonardo Astudillo, Nicole Therville, Lorry Carrié, Magali Pettazzoni, David Cheillan, Jérôme Stirnemann, Thierry Levade, Nathalie Andrieu-Abadie, and Frédérique Sabourdy. “Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer.” Cancers 14, no. 19 (October 5, 2022): 4858. https://doi.org/10.3390/cancers14194858.
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.
Lazar, Ikrame, Emily Clement, Lorry Carrié, David Esteve, Stéphanie Dauvillier, Mohamed Moutahir, Stéphane Dalle, et al. “Adipocyte Extracellular Vesicles Decrease P16INK4A in Melanoma: An Additional Link between Obesity and Cancer.” The Journal of Investigative Dermatology 142, no. 9 (September 2022): 2488-2498.e8. https://doi.org/10.1016/j.jid.2022.01.026.
Fougerat, Anne, Gabriele Schoiswohl, Arnaud Polizzi, Marion Régnier, Carina Wagner, Sarra Smati, Tiffany Fougeray, et al. “ATGL-Dependent White Adipose Tissue Lipolysis Controls Hepatocyte PPARα Activity.” Cell Reports 39, no. 10 (June 7, 2022): 110910. https://doi.org/10.1016/j.celrep.2022.110910.
Germain, Dominique P., Thierry Levade, Eric Hachulla, Bertrand Knebelmann, Didier Lacombe, Vanessa Leguy Seguin, Karine Nguyen, Esther Noël, and Jean-Pierre Rabès. “Challenging the Traditional Approach for Interpreting Genetic Variants: Lessons from Fabry Disease.” Clinical Genetics 101, no. 4 (April 2022): 390–402. https://doi.org/10.1111/cge.14102.
Dummer, Reinhard, Georgina V. Long, Caroline Robert, Hussein A. Tawbi, Keith T. Flaherty, Paolo A. Ascierto, Paul D. Nathan, et al. “Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma.” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, January 14, 2022, JCO2101601. https://doi.org/10.1200/JCO.21.01601.
Pippa, Corrie, Meyer Nicolas, Berardi Rossana, Guidoboni Massimo, Schlueter Maximilian, Kolovos Spyros, Macabeo Bérengère, Trouiller Jean-Baptiste, and Laramée Philippe. “Comparative Efficacy and Safety of Targeted Therapies for BRAF-Mutant Unresectable or Metastatic Melanoma: Results from a Systematic Literature Review and a Network Meta-Analysis.” Cancer Treatment Reviews 110 (2022): 102463. https://doi.org/10.1016/j.ctrv.2022.102463.
PUBLICATIONS 2021
Montfort, Anne, Mathieu Virazels, Céline Colacios, Nicolas Meyer, and Bruno Ségui. “Combining TNF Blockade with Immune Checkpoint Inhibitors in Patients with Cancer.” Nature Reviews. Rheumatology 17, no. 9 (September 2021): 577. https://doi.org/10.1038/s41584-021-00653-8.
Marcheteau, Elie, Thomas Farge, Michaël Pérès, Guillaume Labrousse, Julie Tenet, Stéphanie Delmas, Maud Chusseau, et al. “Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer.” Cancers 13, no. 16 (August 12, 2021): 4059. https://doi.org/10.3390/cancers13164059.
Rabiller, Lise, Virginie Robert, Adèle Arlat, Elodie Labit, Marielle Ousset, Marie Salon, Agnès Coste, et al. “Driving Regeneration, Instead of Healing, in Adult Mammals: The Decisive Role of Resident Macrophages through Efferocytosis.” NPJ Regenerative Medicine 6, no. 1 (August 3, 2021): 41. https://doi.org/10.1038/s41536-021-00151-1.
Montfort, Anne, Florie Bertrand, Julia Rochotte, Julia Gilhodes, Thomas Filleron, Jean Milhès, Carine Dufau, et al. “Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti-PD-1 Therapy Efficacy.” Cancer Immunology Research 9, no. 5 (May 2021): 568–82. https://doi.org/10.1158/2326-6066.CIR-20-0342.
Sacher, Frédéric, Estelle Gandjbakhch, Philippe Maury, Catherine Jenny, Jonathan Khalifa, Serge Boveda, Pascal Defaye, et al. “Focus on Stereotactic Radiotherapy: A New Way to Treat Severe Ventricular Arrhythmias?” Archives of Cardiovascular Diseases 114, no. 2 (February 2021): 140–49. https://doi.org/10.1016/j.acvd.2020.11.003.
PUBLICATIONS 2020
Montfort, Anne, Thomas Filleron, Mathieu Virazels, Carine Dufau, Jean Milhès, Cécile Pages, Pascale Olivier, et al. “Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase 1b Clinical Trial.” Clinical Cancer Research, December 3, 2020, clincanres.3449.2020. https://doi.org/10.1158/1078-0432.CCR-20-3449.
Pellerin, Laurence, Lorry Carrié, Carine Dufau, Laurence Nieto, Bruno Ségui, Thierry Levade, Joëlle Riond, and Nathalie Andrieu-Abadie. “Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.” Cancers 12, no. 11 (October 27, 2020): 3147. https://doi.org/10.3390/cancers12113147.
Carrié, Lorry, Mathieu Virazels, Carine Dufau, Anne Montfort, Thierry Levade, Bruno Ségui, and Nathalie Andrieu-Abadie. “New Insights into the Role of Sphingolipid Metabolism in Melanoma.” Cells 9, no. 9 (August 26, 2020): 1967. https://doi.org/10.3390/cells9091967.
Dubot, Patricia, Leonardo Astudillo, Nicole Therville, Frédérique Sabourdy, Jérôme Stirnemann, Thierry Levade, and Nathalie Andrieu-Abadie. “Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses.” Cancers 12, no. 2 (February 18, 2020). https://doi.org/10.3390/cancers12020475.
Imbert, Caroline, Anne Montfort, Marine Fraisse, Elie Marcheteau, Julia Gilhodes, Elodie Martin, Florie Bertrand, et al. “Resistance of Melanoma to Immune Checkpoint Inhibitors Is Overcome by Targeting the Sphingosine Kinase-1.” Nature Communications 11, no. 1 (January 23, 2020): 437. https://doi.org/10.1038/s41467-019-14218-7.
PUBLICATIONS 2019
Montfort, Anne, Carine Dufau, Céline Colacios, Nathalie Andrieu-Abadie, Thierry Levade, Thomas Filleron, Jean-Pierre Delord, Maha Ayyoub, Nicolas Meyer, and Bruno Ségui. “Anti-TNF, a Magic Bullet in Cancer Immunotherapy?” Journal for Immunotherapy of Cancer 7, no. 1 (November 14, 2019): 303. https://doi.org/10.1186/s40425-019-0802-y.
Dubot, Patricia, Frédérique Sabourdy, Jitka Rybova, Jeffrey A. Medin, and Thierry Levade. “Inherited Monogenic Defects of Ceramide Metabolism: Molecular Bases and Diagnoses.” Clinica Chimica Acta; International Journal of Clinical Chemistry 495 (August 2019): 457–66. https://doi.org/10.1016/j.cca.2019.05.020.
Baudoin-Dehoux, Cécile, Tessa Castellan, Frédéric Rodriguez, Arnaud Rives, Fabien Stauffert, Virginie Garcia, Thierry Levade, Philippe Compain, and Yves Génisson. “Selective Targeting of the Interconversion between Glucosylceramide and Ceramide by Scaffold Tailoring of Iminosugar Inhibitors.” Molecules (Basel, Switzerland) 24, no. 2 (January 19, 2019): 354. https://doi.org/10.3390/molecules24020354.
Alaeddine, Mohamad, Mélissa Prat, Véréna Hauke Poinsot, Valérie Gouazé-Andersson, Hélène Authier, Etienne Meunier, Lise Lefèvre, et al. “IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells.” Cancer Immunology Research, January 4, 2019. https://doi.org/10.1158/2326-6066.CIR-18-0213.
Leclerc, Justine, David Garandeau, Charlotte Pandiani, Céline Gaudel, Karine Bille, Nicolas Nottet, Virginie Garcia, et al. “Lysosomal Acid Ceramidase ASAH1 Controls the Transition between Invasive and Proliferative Phenotype in Melanoma Cells.” Oncogene 38, no. 8 (2019): 1282–95. https://doi.org/10.1038/s41388-018-0500-0.
Garandeau, David, Justine Noujarède, Justine Leclerc, Caroline Imbert, Virginie Garcia, Marie-Lise Bats, Florian Rambow, et al. “Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas.” Molecular Cancer Therapeutics 18, no. 2 (2019): 289–300. https://doi.org/10.1158/1535-7163.MCT-17-1141.
Montfort, Anne, Céline Colacios, Thierry Levade, Nathalie Andrieu-Abadie, Nicolas Meyer, and Bruno Ségui. “Corrigendum: The TNF Paradox in Cancer Progression and Immunotherapy.” Frontiers in Immunology 10 (2019): 2515. https://doi.org/10.3389/fimmu.2019.02515.
Montfort, Anne, Céline Colacios, Thierry Levade, Nathalie Andrieu-Abadie, Nicolas Meyer, and Bruno Ségui. “The TNF Paradox in Cancer Progression and Immunotherapy.” Frontiers in Immunology 10 (2019): 1818. https://doi.org/10.3389/fimmu.2019.01818.
Bilal, Fatima, Anne Montfort, Julia Gilhodes, Virginie Garcia, Joëlle Riond, Stéphane Carpentier, Thomas Filleron, et al. “Sphingomyelin Synthase 1 (SMS1) Downregulation Is Associated With Sphingolipid Reprogramming and a Worse Prognosis in Melanoma.” Frontiers in Pharmacology 10 (2019): 443. https://doi.org/10.3389/fphar.2019.00443.

LES MEMBRES DE L’ÉQUIPE

Aimie Fauré
Doctorant / PhD student
Tania Margarido Pereira
Doctorant / PhD student
Océane DAINESE-MARQUE
Doctorant / PhD student
Benjamin Jung
Doctorant / PhD student
Frédérique Sabourdy
Enseignant chercheur / University researcher
Stéphanie Brayer
Clinicien Chercheur / Researcher hospital practitioner
Marie Tosolini
Ingénieur de laboratoire / laboratory engineer
Lorry Carrié
Doctorant / PhD student
Patricia Clave
Technicien de laboratoire / Laboratory Technician
Stéphane Carpentier
Technicien de laboratoire / Laboratory Technician
Laura Leroy
Ingénieur de laboratoire / laboratory engineer
Bruno Segui
Chercheur statutaire / permanent scientist
Virginie Garcia
Ingénieur de laboratoire / laboratory engineer
Thierry Levade
Hospitalo-Universitaire / University teacher hospital practitioner
Nathalie Andrieu
Chercheur statutaire / permanent scientist
Elodie Mucher
Ingénieur de laboratoire / laboratory engineer
Joëlle Riond
Chercheur statutaire / permanent scientist
Laurence Nieto
Enseignant chercheur / University researcher
Anne Montfort
Chercheur statutaire / permanent scientist
Mathieu Virazels
Doctorant / PhD student
12

LES PARTENAIRES & FINANCIERS

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches en Cancérologie de Toulouse (Oncopole)

Toulouse – FR

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