Team 9
ChromatIn and transcriptionaL Deregulation in pediatric bone sarcoma
Team leaders : Benjamin Ory et François Lamoureux
Educational videos in french available!
Our project
The work of our research team is dedicated to understanding the molecular and cellular mechanisms involved in the development of pediatric sarcomas : Rhabdomyosarcoma and primary bone tumors such as Osteosarcoma (OS) and Ewing sarcoma (ES).
French incidence rates from 2012 to 2016 and french survival rate from 2000 to 2016 below. Rhabdomyosarcoma is more present in young children whereas Osteosarcoma and Ewing sarcoma are more present in pre-adolescents. Source
Our research program aims in particular to study the epigenetic and transcriptional regulations involved in the development of these pediatric tumors. We focus more particularly on the metastatic dissemination of these cells as well as on their resistance to chemotherapy treatments, which constitute poor prognostic factors in patients.The objective of our work is to identify new therapeutic targets in order to improve the efficiency of the therapeutic management of patients with pediatric sarcomas.
You can see below our two axis of research :
- BET proteins and Super-Enhancers implications in chromatin and transcriptional regulation
- Transcription factor activity and extracellular Stresses
We use an association of various in vitro models, in vivo models, PDX, patient samples, single cells and bioinformatics tools. Some examples are below.
Want to learn more about our projects? Check out our educational videos (available in french only).
France 3 TV Interview (October 17, 2023, in French)
We would like to express our sincere gratitude to France 3 TV for hosting this interview on October 17, 2023. We would also like to extend our appreciation to Imagine for Margo and the Rallye du Coeur, who were both prominently featured in the interview.
Latest News
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For Golden September 2025 (Paediatric Cancer Awareness Month), we are participating in several activities. More on our LinkedIn.
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On the 15th of February 2025 (International Childhood Cancer Day), we have participated in several actions. More on our Linkedin.
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We are thrilled to share that our latest article Transcriptional regulation of KCNA2 coding Kv1.2 by EWS::FLI1: involvement in controlling the YAP/Hippo signalling pathway and cell proliferation has just been published!
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Congratulations to Morgane Lallier who defended her PhD the 08/11/2024 on the role of transcription factor HSF1 in osteosarcoma development and progression.
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Our newest research article Chimeric protein EWS::FLI1 drives cell proliferation in Ewing Sarcoma via aberrant expression of KCNN1/SK1 and dysregulation of calcium signaling is now published! Explore our latest discoveries.
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Check out our lastest review : Super-enhancers: drivers of cells' identities and cells' debacles.
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Congratulations to Emma Racineau who got a prize for her poster at the React4kids seminar !
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Professor Ory recently conducted an interview on the topic of sarcoma research. You can watch the video below.
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Congratulations to Maryne Dupuy who defended her PhD the 06/07/2023 on the Epigenetic and transcriptional regulation of KCNN1 and KCNA2 by the EWS-FLI1 fusion protein: role in the control of Ewing's sarcoma cell proliferation.
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Check out our latest article : Tracking Targets of Dynamic Super-Enhancers in Vitro to Better Characterize Osteoclastogenesis and to Evaluate the Effect of Diuron on the Maturation of Human Bone Cells
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Congratulations to Émilien Orgebin who defended his PhD the 26/06/2023 on the Involvement of a variant of the RPL13 protein (eL13) in the development of constitutional bone disease.
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Some members of the team went to the JFBTM from the 22/05/2023 to the 24/05/2023. Morgane Lallier had an oral communication about her work, Maryne Dupuy presented two posters and received a prize.
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Take a look to our latest publication : TRAIL-Based Therapies Efficacy in Pediatric Bone Tumors Models Is Modulated by TRAIL Non-Apoptotic Pathway Activation via RIPK1 Recruitment.
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Congratulations to our Doctors !
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Louise Marchandet defended her PhD on "Mechanisms of resistance to bromodomain and extra-terminal domain proteins inhibitors in osteosarcoma" the 12th December 2022.
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Mélanie Lavaud defended her PhD on "Identification of key actors involved in bone tissue development and osteosarcoma progression by studies of active super-enhancers" the 26th October 2022.
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Robel Tesfaye defended his PhD on "Multi-sample analysis of dynamic super-enhancers to better characterize normal bone development and osteosarcoma evolution" the 19th October 2022.
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Contact us
Faculté de Médecine
1 rue Gaston Veil
44 035 Nantes cedex 1
France
Tel 1 : 02 44 76 91 02
Tel 2 : 02 44 76 91 07
Our members
| Researchers Benjamin Ory, PU, HDR François Lamoureux, CR Inserm, HDR Franck Verrecchia, DR Inserm, HDR Bénédicte Brounais-Le-Royer, MCU Steven Georges, MCU Marc Baud’huin, PU-PH, HDR Clinicians Vincent Crenn, PU-PH, HDR Helios Bertin, MCU-PH Morgane Cleirec, PH |
Technical team Régis Brion, IE Rose-Anne Thepault, TR Céline Charrier, AI Séverine Battaglia, IE Jérôme Amiaud, AI Frédéric Jacquot, IR Anaïs Postec, IE Mathilde Mullard, IE Fanny Quiquempoix, AI |
Students Emma Racineau, PhD Candidate Léa Lassous, PhD Candidate Edith Loisy, PhD Candidate Shah Raja Muhammad, Medical resident Amina Al Hamka, M2 Malorie Métairie, M2 Souha Amri, M2 |
Offers
Scientific equipment
- Microtomograph (or Micro-CT) in vivo Bruker - Skyscan 1276 dedicated to the study of small animals.
- Non-destructive 3D X-ray imaging technique of a sample.
- Software specific to 2D reconstruction, 3D volume rendering, and image analysis.
- Expertise in anatomical exploration : analysis of bone microarchitecture.
Microtomograph 1276 is Property of Nantes Université since october 2021, it is co-funded by FEDER in Région Pays de La Loire and La Ligue contre le Cancer 44.
Funding
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Associations
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Network
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| National level: SFCE (French Society for Childhood Cancers) |
National network React4Kids (basic research on pediatric cancers) |
Share4Kids project (labelled by INCa) |
Responsible for a work package of the project led by the BoOST-Data consortium (labelled by INCa) aiming at developing specific databases for pediatric tumors |
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Racineau E, Lallier M, Postec A, Amiaud J, Thépault R, Brion R, Battaglia S, Charrier C, Colle M, Brounais-Le Royer B, Baud'huin M, Verrecchia F, Ory B, Georges S, Lamoureux F. Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma. Cell Death Discovery, Jan 2026. doi: https://doi.org/10.1038/s41420-026-02941-2. PMID: 41644942.
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Dupuy M, Postec A, Mullard M, Chantôme A, Hulin P, Brion R, Gueguinou M, Regnier L, Potier-Cartereau M, Brounais-Le Royer B, Baud’huin M, Georges S, Lamoureux F, Ory B, Rédini F, Vandier C, Verrecchia F. Transcriptional regulation of KCNA2 coding Kv1.2 by EWS::FLI1: involvement in controlling the YAP/Hippo signalling pathway and cell proliferation. Cell Communication and Signaling, Dec 2024. doi: https://doi.org/10.1186/s12964-024-01981-4. PMID: 39695664.
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Dupuy M, Gueguinou M, Postec A, Brion R, Tesfaye R, Mullard M, Regnier L, Amiaud J, Hubsch C, Potier-Cartereau M, Chantôme A, Brounais-Le Royer B, Baud’huin M, Georges S, Lamoureux F, Ory B, Entz-Werlé N, Delattre O, Rédini F, Vandier C, Verrecchia F. Chimeric protein EWS::FLI1 drives cell proliferation in Ewing Sarcoma via aberrant expression of KCNN1/SK1 and dysregulation of calcium signaling. Oncogene, Nov 2024, 1‑13. doi: https://doi.org/10.1038/s41388-024-03199-7. PMID: 39487324.
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Dupuy M, Gueguinou M, Potier-Cartereau M, Lézot F, Papin M, Chantôme A, Redini F, Vandier C, Verrecchia F. SKCa- and Kv1-type potassium channels and cancer: Promising therapeutic targets ? Biochemical Pharmacology, Sep 2023. doi: https://doi.org/10.1016/j.bcp.2023.115774. PMID: 37678626.
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Dupuy M, Lamoureux F, Mullard M, Postec A, Regnier L, Baud'huin M, Georges S, Brounais-Le Royer B, Ory B, Redini F, Verrecchia F. Ewing sarcoma from molecular biology to the clinic. Front. Cell Dev. Biol., 2023 Sep. doi: https://doi.org/10.3389/fcell.2023.1248753.
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Tesfaye R, Lavaud M, Charrier C, Brounais-Le Royer B, Cartron PF, Verrecchia F, Baud'huin M, Lamoureux F, Georges S, Ory B. Tracking Targets of Dynamic Super-Enhancers in Vitro to Better Characterize Osteoclastogenesis and to Evaluate the Effect of Diuron on the Maturation of Human Bone Cells. Environ Health Perspect. 2023 Jun; 131(6): 067007. doi: https://doi.org/10.1289/EHP11690. PMID: 37307168. PMCID: PMC10259763.
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Brion R, Gantier M, Biteau K, Taurelle J, Brounais-Le Royer B, Verrecchia F, Rédini F, Guiho R. TRAIL-Based Therapies Efficacy in Pediatric Bone Tumors Models Is Modulated by TRAIL Non-Apoptotic Pathway Activation via RIPK1 Recruitment. Cancers (Basel). 2022 Nov 16;14(22):5627. doi: 10.3390/cancers14225627. PMID: 36428719; PMCID: PMC9688679.
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Moukengue B, Lallier M, Marchandet L, Baud'huin M, Verrecchia F, Ory B, Lamoureux F. Origin and Therapies of Osteosarcoma. Cancers (Basel). 2022 Jul 19;14(14):3503. doi: 10.3390/cancers14143503. PMID: 35884563; PMCID: PMC9322921.
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Rodriguez Calleja L, Lavaud M, Tesfaye R, Brounais-Le-Royer B, Baud'huin M, Georges S, Lamoureux F, Verrecchia F, Ory B. The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway. Cancers (Basel). 2022 Dec 1;14(23):5948. doi: 10.3390/cancers14235948. PMID: 36497429; PMCID: PMC9741383.
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Crenn V, Amiaud J, Gomez-Brouchet A, Potiron V, Gouin F, Rosset P, Nail LL, Vidal L, Bertin H, Brion R, Tran G, Verrecchia F, Corre I, Redini F. Signature of the vascular tumor microenvironment as a marker of the therapeutic response to doxorubicin in a preclinical model of osteosarcoma. Am J Cancer Res. 2022 Apr 15;12(4):1843-1854. PMID: 35530297; PMCID: PMC9077066.
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Marchais A, Marques da Costa ME, Job B, Abbas R, Drubay D, Piperno-Neumann S, Fromigué O, Gomez-Brouchet A, Redini F, Droit R, Lervat C, Entz-Werle N, Pacquement H, Devoldere C, Cupissol D, Bodet D, Gandemer V, Berger M, Marec-Berard P, Jimenez M, Vassal G, Geoerger B, Brugières L, Gaspar N. Immune Infiltrate and Tumor Microenvironment Transcriptional Programs Stratify Pediatric Osteosarcoma into Prognostic Groups at Diagnosis. Cancer Res. 2022 Mar 15;82(6):974-985. doi: 10.1158/0008-5472.CAN-20-4189. PMID: 35078815.
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Veys C, Jammes M, Rédini F, Poulain L, Denoyelle C, Legendre F, Galera P. Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells. Pharmaceuticals (Basel). 2022 Mar 16;15(3):362. doi: 10.3390/ph15030362. PMID: 35337159; PMCID: PMC8949568.
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Nazon C, Pierrevelcin M, Willaume T, Lhermitte B, Weingertner N, Marco AD, Bund L, Vincent F, Bierry G, Gomez-Brouchet A, Redini F, Gaspar N, Dontenwill M, Entz-Werle N. Together Intra-Tumor Hypoxia and Macrophagic Immunity Are Driven Worst Outcome in Pediatric High-Grade Osteosarcomas. Cancers (Basel). 2022 Mar 14;14(6):1482. doi: 10.3390/cancers14061482. PMID: 35326631; PMCID: PMC8945994.
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Muñoz-Garcia J, Vargas-Franco JW, Royer BB, Cochonneau D, Amiaud J, Heymann MF, Heymann D, Lézot F. Inhibiting Endothelin Receptors with Macitentan Strengthens the Bone Protective Action of RANKL Inhibition and Reduces Metastatic Dissemination in Osteosarcoma. Cancers (Basel). 2022 Mar 30;14(7):1765. doi: 10.3390/cancers14071765. PMID: 35406536; PMCID: PMC8997105.