Research Projects

On the ground of our interests for molecular piracy exerted by tumor cells to survive, adapt and remodel their environment, we explore the signaling mechanisms involved in non-oncogene addiction and loss of vascular homeostasis.

1. Cell-Cell Interactions.
Within the tumor microenvironment, endothelial cells occupy a privileged exchange function with tumor cells, where they provide energy, oxygen, trophic factors and a direct access to bloodstream. We explore how cell-cell adhesion molecules enhance the physical and functional interactions between tumor cells and endothelial cells, favoring localized paracrine communication.

2. Intracellular Signaling and Post-Translational Modifications.
The tumor microenvironment is often characterized by an aberrant activation of the signaling pathway leading to the NF-KB transcription factor. Modulation of these cascades is notably finely regulated by ubiquitination, a reversible post-translational modification that corresponds to the covalent addition of ubiquitin chains. Our group is researching the impact of these modifications on cellular signaling and homeostasis.

3. Extracellular Communication and Vesicles.
Extracellular vesicles (EVs) are a preferred mode of communication between tumor cells and their microenvironment. These vesicles are detectable in the general circulation and their contents reflect the general state of the tumor, in particular responses to treatments. We examine the mechanisms of vesicle production and dissemination, as well as changes in their cargo.

Overall, our team combines cell biology and biochemistry approaches to identify new control points for tumor communication and thus characterize potentially relevant targets for the development of clinical treatments and diagnostic tools.

Staff

Julie Gavard, Research Director CNRS
Nicolas Bidère, Research Director INSERM

Isabelle Corre, Associate Researcher CNRS, HDR
Gwennan André-Grégoire, Staff ICO
Laetitia Guével, Associate Professor Nantes Univ, HDR

Carolina Nicolau, Post-Doc
Sara Rosinska, Post-Doc
Fiorella Spinelli, Post-Doc
Jane Jardine, Post-Doc

Kilian Trillet, IE INSERM

Clément Maghe, PhD student
Clothilde Renaud, PhD student
Mathilde Kerhervé, PhD student
Mathilde Richard, PhD student
Yanis Macé, PhD student

Margaux Le Guyon, Pharm Sc Angers
Lucille Allen, MSc Nantes
Léandre Erussard, MSc Rennes
Laura Merlet, MSc Poitiers

Main Publications

– Trillet K, Jacobs KA, André-Grégoire G, Thys A, Maghe C, Cruard J, Minvielle S, Gonzales Diest S, Montagnac G, Bidère N, Gavard J. The glycoprotein GP130 governs the surface presentation of the G-protein coupled receptor APLNR. J Cell Biol 2021; 220(9):e202004114.
– Rosinska S, Gavard J. Tumor Vessels Fuel the Fire in Glioblastoma. Int J Mol Sci 2021; 22(12), 6514.
– Thys A, Trillet K, Rosinska S, Gayraud A, Douanne T, Danger Y, Renaud CCN, Antigny L, Lavigne R, Pineau C, Com E, Vérité F, Gavard J, Bidère N. Serine 165 Phosphorylation of SHARPIN regulates the Activation of NF-κB. iScience 2020; 24(1): 101939. https://hal.archives-ouvertes.fr/hal-03099208
– Alves Nicolau C, Gavard J, Bidere N. TAK1 lessens the Activity of the Paracaspase MALT1 during T cell Receptor Signaling. Cell Immunol 2020; 353: 104115. https://www.hal.inserm.fr/inserm-02558368
– Jacobs KA, André-Grégoire G, Maghe C, Li Y, Thys A, Harford-Wright E, Trillet K, Douanne T, Frenel JS, Bidere N, Gavard J. Paracaspase MALT1 regulates glioma cell survival by controlling endo-lysosome homeostasis. EMBO J 2020; e102030. https://www.hal.inserm.fr/inserm-02395350v1
– Douanne T, André-Grégoire G, Trillet K, Thys A, Papin A, Feyeux M, Hulin P, Chiron D, Gavard J, Bidere N. Pannexin-1 limits the production of proinflammatory cytokines during necroptosis. EMBO Rep 2019; 20(10): e47840. https://www.hal.inserm.fr/inserm-02281304v1
– Douanne T, André-Grégoire G, Thys A, Trillet K, Gavard J, Bidère N. CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1. Cell Reports 2019: 27(6): 1657-65. https://www.hal.inserm.fr/inserm-02128157
– Duarte A, André-Grégoire G, Trillet K, Thys A, Bidère N, Ribeiro-Silva A, Gavard J. Inhibition of mTOR in Head and Neck Cancer Cells Alters Endothelial Cell Morphology in a Paracrine Fashion. Mol Carcinogenesis 2019; 58: 161-8. https://www.hal.inserm.fr/inserm-01908781v1
– Thys A, Douanne T, Bidere N. Post-translational Modifications of the CARMA1-BCL10-MALT1 Complex in Lymphocytes and Activated B-cell Like Subtype of Diffuse Large B-cell Lymphoma. Front Oncol 2018; 8: 498. https://www.hal.inserm.fr/inserm-01908802v1
– Roux Q, Gavard J. Endothelial Cell-Cell Junctions in Tumor Angiogenesis. In: Marmé D. (eds) Tumor Angiogenesis Springer, Cham doi.org/10.1007/978-3-319-3125-6_39-1
– André-Grégoire G, Bidère N, Gavard J. Temozolomide Affects Extracellular Vesicles Released by Glioblastoma Cells. Biochimie 2018; pii: S0300-9084(18)30041-5. https://www.hal.inserm.fr/inserm-01715956v1
– Jacobs KA, Gavard J. 3D endothelial migration. Methods Mol Biol 2018; 1749: 51-58.
– Harford-Wright E, Gavard J. Apelin, the Devil Inside Brain Tumors. J Exp Neurosci 2018; 12: 1-3. https://www.hal.inserm.fr/inserm-01810684v1
– Harford-Wright E, Andre-Gregoire G, Jacobs KA, Treps L, Le Gonidec S, Leclair HM, Gonzalez-Diest S, Roux Q, Guillonneau F, Loussouarn D, Oliver L, Vallette FM, Foufelle F, Valet P, Davenport AP, Glen RC, Bidere N, Gavard J. Pharmacological targeting of apelin impairs glioblastoma growth. Brain 2017; 140(11): 2939-54. http://www.hal.inserm.fr/inserm-01611131v1
– Treps L, Perret R, Edmond S, Ricard D, Gavard J. Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles. J Extracell Ves 2017; 1(6). http://www.hal.inserm.fr/inserm-01573268v1
– Jacobs KA, Harford-Wright E, Gavard J. Neutralizing gp130 interferes with endothelial-mediated effects on glioblastoma stem-like cells. Cell Death Diff 2017; 24(2): 384. http://www.hal.inserm.fr/inserm-01444543v1
– Harford-Wright E, Bidere N, Gavard J. β-escin selectively targets glioblastoma-initiating cell identity to reduce cell viability. Oncotarget 2016; 7(41): 66865-79. http://www.hal.inserm.fr/inserm-01385219
– Douanne T, Gavard J, Bidère N. The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling. J Cell Sci 2016; 129(9): 1775-80. http://www.hal.inserm.fr/inserm-01311283
– Treps L, Edmond S, Harford-Wright E, Galan-Moya EM, Schmitt A, Azzi S, Citerne A, Bidere N, Ricard D, Gavard J. Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. Oncogene 2016; 35, 2615-23. http://www.hal.inserm.fr/inserm-01406334v1
– Dubois SM, Alexia C, Wu Y, Leclair HM, Leveau C, Schol E, Fest T, Tarte K, Chen Z, Gavard J, Bidere N. A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells. Blood 2014; 123(14): 2199-203.
– Azzi S, Smith SS, Dwyer J, Leclair HM, Alexia C, Hebda JK, Dupin N, Bidere N, Gavard J. YGLF motif in the Kaposi Sarcoma Herpes Virus G protein coupled receptor adjusts NF-κB activation and paracrine actions. Oncogene 2014; 33(49): 5609-18. https://www.hal.inserm.fr/inserm-01078184v1
– Alexia C, Poalas K, Carvalho G, Zermili N, Dwyer J, Dubois SM, Hatchi EM, Cordeiro N, Smith SS, Castanier C, Le Guelte A, Wan L, Kang Y, Vazquez A, Gavard J, Arnoult D, Bidere N. The endoplasmic reticulum acts as a platform for ubiquitylated components of Nuclear Factor-κB signaling. Sci Signal 2013; 6: ra79.
– Le Guelte A, Galan-Moya EM, Dwyer J, Treps L, Kettler G, Hebda JK, Dubois S, Auffray C, Chneiweiss H, Bidere N, Gavard J. Semaphorin 3A elevates endothelial cell permeability through PP2A inactivation. J Cell Sci 2012; 125: 4137-46.
– Galan-Moya EM, Le Guelte A, Lima Fernandes E, Thirant C, Dwyer J, Bidere N, Couraud PO, Scott MG, Junier MP, Chneiweiss H, Gavard J. Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Rep 2011; 12(5): 470-6.

  • Julie Gavard
  • Nantes-Angers Research Center for Cancer and Integrated Immunology
  • Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1
  • 033 02 28 08 03 27
  • julie.gavard@inserm.fr