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L'unité en quelques chiffres clés :
![]() Créé en 2022 |
![]() 82 membres |
![]() 5 équipes de recherche |
![]() 265 publications (2015-2024) |
![]() 43 soutenances de thèse (2015-2024) |
Les équipes :
Publications récentes :
Roman, Dávid; Meisinger, Philippe; Guillonneau, Richard; Peng, Chia-Chi; Peltner, Lukas K; Jordan, Paul M; Haensch, Veit; Götze, Sebastian; Werz, Oliver; Hertweck, Christian; Chen, Yin; Beemelmanns, Christine
Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis Article de journal
Dans: Angew Chem Int Ed Engl, vol. 63, no. 23, p. e202401195, 2024, ISSN: 1521-3773.
@article{pmid38529534,
title = {Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis},
author = {Dávid Roman and Philippe Meisinger and Richard Guillonneau and Chia-Chi Peng and Lukas K Peltner and Paul M Jordan and Veit Haensch and Sebastian Götze and Oliver Werz and Christian Hertweck and Yin Chen and Christine Beemelmanns},
url = { hal-04587238v1 },
doi = {10.1002/anie.202401195},
issn = {1521-3773},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Angew Chem Int Ed Engl},
volume = {63},
number = {23},
pages = {e202401195},
abstract = {The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur-containing amino lipids (SALs) involved in biofilm formation and marine surface colonization processes. Despite their physiological relevance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved, hindering progress in biochemical and functional investigations. Herein, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine-based structures, cysteinolides are composed of an N,O-acylated cysteinolic acid-containing head group carrying various different (α-hydroxy)carboxylic acids. We also performed the first validated targeted-network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insight, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cordova, Luis A.; González-Quintanilla, David; Heymann, Dominique
Why are osteoporosis patients treated with antiresorptive therapies considered like oncology patients regarding their oral health care? Article de journal
Dans: Osteoporosis International, 2024, ISSN: 1433-2965.
@article{cordova_why_2024,
title = {Why are osteoporosis patients treated with antiresorptive therapies considered like oncology patients regarding their oral health care?},
author = {Luis A. Cordova and David González-Quintanilla and Dominique Heymann},
url = {https://doi.org/10.1007/s00198-024-07173-7},
doi = {10.1007/s00198-024-07173-7},
issn = {1433-2965},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Osteoporosis International},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rey, Verónica; Tornín, Juan; Alba-Linares, Juan Jose; Robledo, Cristina; Murillo, Dzohara; Rodríguez, Aida; Gallego, Borja; Huergo, Carmen; Viera, Cristina; Braña, Alejandro; Astudillo, Aurora; Heymann, Dominique; Szuhai, Karoly; Bovée, Judith V M G; Fernández, Agustín F; Fraga, Mario F; Alonso, Javier; Rodríguez, René
A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma Article de journal
Dans: EBioMedicine, vol. 102, p. 105090, 2024, ISSN: 2352-3964.
@article{pmid38547578b,
title = {A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma},
author = {Verónica Rey and Juan Tornín and Juan Jose Alba-Linares and Cristina Robledo and Dzohara Murillo and Aida Rodríguez and Borja Gallego and Carmen Huergo and Cristina Viera and Alejandro Braña and Aurora Astudillo and Dominique Heymann and Karoly Szuhai and Judith V M G Bovée and Agustín F Fernández and Mario F Fraga and Javier Alonso and René Rodríguez},
url = {inserm-04524777v1 },
doi = {10.1016/j.ebiom.2024.105090},
issn = {2352-3964},
year = {2024},
date = {2024-04-01},
urldate = {2024-04-01},
journal = {EBioMedicine},
volume = {102},
pages = {105090},
abstract = {BACKGROUND: Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumours do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumour growth.
METHODS: We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses).
FINDINGS: We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors.
INTERPRETATION: Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.
FUNDING: Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses).
FINDINGS: We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors.
INTERPRETATION: Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.
FUNDING: Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).
Evin, Manon; Koumeir, Charbel; Bongrand, Arthur; Delpon, Gregory; Haddad, Ferid; Mouchard, Quentin; Potiron, Vincent; Saade, Gaëlle; Servagent, Noël; Villoing, Daphnée; Métivier, Vincent; Chiavassa, Sophie
Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam Article de journal
Dans: Phys Med, vol. 120, p. 103332, 2024, ISSN: 1724-191X.
@article{pmid38518627,
title = {Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam},
author = {Manon Evin and Charbel Koumeir and Arthur Bongrand and Gregory Delpon and Ferid Haddad and Quentin Mouchard and Vincent Potiron and Gaëlle Saade and Noël Servagent and Daphnée Villoing and Vincent Métivier and Sophie Chiavassa},
url = { hal-04556782v1 },
doi = {10.1016/j.ejmp.2024.103332},
issn = {1724-191X},
year = {2024},
date = {2024-04-01},
urldate = {2024-04-01},
journal = {Phys Med},
volume = {120},
pages = {103332},
abstract = {As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal. A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated. The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting. The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Agranier, Eva; Crétin, Pauline; Joublin-Delavat, Aurélie; Veillard, Léa; Touahri, Katia; Delavat, François
Development and utilization of new O2-independent bioreporters Article de journal
Dans: Microbiology Spectrum, vol. 0, no. 0, p. e04091-23, 2024.
@article{doi:10.1128/spectrum.04091-23,
title = {Development and utilization of new O_{2}-independent bioreporters},
author = {Eva Agranier and Pauline Crétin and Aurélie Joublin-Delavat and Léa Veillard and Katia Touahri and François Delavat},
url = {https://journals.asm.org/doi/abs/10.1128/spectrum.04091-23
hal-04505221v1 },
doi = {10.1128/spectrum.04091-23},
year = {2024},
date = {2024-03-05},
urldate = {2024-03-05},
journal = {Microbiology Spectrum},
volume = {0},
number = {0},
pages = {e04091-23},
abstract = {Fluorescent proteins are used for decades, and have allowed major discoveries in biology in a wide variety of fields, and are used in environmental as well as clinical contexts. Green fluorescent protein (GFP) and all its derivatives share a common feature: they rely on the presence of dioxygen (O2) for protein maturation and fluorescence. This dependency precludes their use in anoxic environments. Here, we constructed a series of genetic circuits allowing production of KOFP-7, an O2-independant flavin-binding fluorescent protein. We demonstrated that Escherichia coli cells producing KOFP-7 are fluorescent, both at the population and single-cell levels. Importantly, we showed that, unlike cells producing GFP, cells producing KOFP-7 are fluorescent in anoxia. Finally, we demonstrated that Vibrio diazotrophicus NS1, a facultative anaerobe, is fluorescent in the absence of O2 when KOFP-7 is produced. Altogether, the development of new genetic circuits allowing O2-independent fluorescence will open new perspective to study anaerobic processes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}