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SEMINAIRE EXTERNE IRCM

Ana Pardo-Saganta, PhDProfessor Lung Inflammation and RepairInstitute for Lung Health - Justus Liebig University German Center for Lung Research, GIESSEN (Germany)"Coordinated healing: heterotypic cellular interactions in lung injury and repair"host : A. MARAVER (IRCM)Chronic lung disease such as IPF or COPD develops over extended periods of time and arecharacterized by failure in mechanisms of repair (1,2). Both pathologies are considered age-relateddiseases exhibiting most of the hallmarks of aging including stem cell exhaustion and alteredintercellular communication (3). In the last years, novel epithelial progenitor cells have been identifiedand demonstrated to contribute to lung repair. In fact, distinct subpopulations of alveolar type (AT) 2cells have been shown to have higher regenerative capacity (4-8). Recent findings shed light to themechanisms of regeneration of the alveolar epithelium (8-11); however, a better understanding of thecoordinated processes of tissue repair from different stem cell pools after injury is crucial to restorethe delicate lung architecture. Our research focuses on the study of the interplay between theseepithelial progenitor populations and neighboring cell types of their microenvironment in thedevelopment of lung disease.It is now generally accepted that epithelial cell loss or dysfunction drives the development of lungfibrosis (12-15). We have identified an additional function for AT2 cells that in addition to serve asadult stem cells of the alveolar epithelium can play a profibrotic role directly activating adjacentfibroblast. This communication is mediated by the Notch pathway and their blockade seems toattenuate the fibrotic phenotype, revealing a potential therapy for IPF, a fatal disease with no cure, amedian survival of 3-5 years post-diagnosis and whose incidence in increasing in the last years (1).Thus, our findings support the notion that the pathophysiology of pulmonary fibrosis relies in part, onthe Notch-regulated interaction between aberrant cellular populations of the fibrotic lung and thatunravelling this complex microenvironment is critical to find efficient treatments for IPF.References1. Schneider JL, et al. The aging lung: physiology, disease and immunity. Cell. 2021 Apr15;184(8):1990-2019. doi: 10.1016/j.cell.2021.03.005.2. Han S, et al. Alveolar epithelial regeneration in the aging lung. .J Clin Invest. 2023 Oct16;133(20):e170504. doi: 10.1172/JCI1705043. Lopez-Otin C. et al. Hallmarks of aging: An expanding universe. Cell 2023, Jan 19;186(2):243-278.doi: 10.1016/j.cell.2022.11.0014. Zacharias WJ. et al, Nature 2018 Mar 8;555(7695):251-255. doi: 10.1038/nature25786.5. Nabhan AN. et al., Science 2018 Mar 9;359(6380):1118-1123. doi: 10.1126/science.aam66036. Chen et al., Am J Physiol Lung Cell Mol Physiol. 2017 Jul 1;313(1):L41-L51. doi:10.1152/ajplung.00564.2016.7. Ahmadvand N. et al., Eur Respir J. 2021 Nov 4;58(5):2004168. doi: 10.1183/13993003.04168-2020.8. Choi J. et al., Cell Stem Cell 2020 Sep 3;27(3):366-382.e7. doi: 10.1016/j.stem.2020.06.020.9. Kobayashi Y. et al, Nat Cell Biol 2020 Aug;22(8):934-946. doi: 10.1038/s41556-020-0542-8.10. Strunz M. et al., Nat Comm 2020. Jul 16;11(1):3559. doi: 10.1038/s41467-020-17358-3.11. Jiang P. et al., Am J Respir Crit Care Med. 2020 Jun 1;201(11):1443-1447. doi:10.1164/rccm.201909-1726LE.12. Sakai, N. & Tager, A. M. Fibrosis of two: Epithelial cell-fibroblast interactions in pulmonaryfibrosis. Biochim. Biophys. Acta - Mol. Basis Dis. 1832, 911–921 (2013).13. Barkauskas, C. E. & Noble, P. W. Cellular Mechanisms of Tissue Fibrosis. 7. New insights into thecellular mechanisms of pulmonary fibrosis. AJP Cell Physiol. 306, C987–C996 (2014).14. Xie T. et al. Abnormal respiratory progenitors in fibrotic lung injury. Stem Cell Res Ther.;13(1):64(2022).15. Konkimalla A, et al. Lung Regeneration: Cells, Models, and Mechanisms. Cold Spring HarbPerspect Biol.; a040873 (2021).

SEMINAIRE IRCM 20 Fevrier 2026

Michel COHEN-TANNOUDJIInstitut Pasteur (Paris)"When Retrotransposons and Immune Ribonucleases Shape Speciation: The Case of The Maternal Hybrid Incompatibility of the Mouse DDK Strain"hosts: Alexandre David & Laurent Le Cam (IRCM)

SEMINAIRE EXTERNE LUNDI 15 DECEMBRE 16H (EPIDAURE)

Luca GRUMOLATOROUEN University, INSERM U982"Tracking cell heterogeneity to investigate lung cancer acquired resistance to EGFR-TKIs"host : A. Maraver (IRCM)

CALL FOR NEW GROUP LEADERS @ IRCM

The IRCM is recruiting new group leaders to establish world-class research programs withinan interactive and supportive scientific environment. Applicants demonstrating potentialsynergies with IRCM’s main research topics will be considered for starting an independentteam as soon as January 2027. Projects at the interface of fundamental and clinical research,particularly those focused on the ICM's flagship pathologies, will be given carefulconsideration. We welcome senior team leaders with permanent INSERM / CNRS positionsas well as early-career researchers eligible to ERC, INSERM ATIP-AVENIR and FRM start-upgrants. MORE INFORMATIONS HERE

the word of the director

"Together, let's push the limits."

"In barely 20 years, the Institut de Recherche en Cancérologie de Montpellier (IRCM U1194) has succeeded in raising its research to the highest international level in the field of fundamental and applied cancer research, carried out in close collaboration with the clinical departments of the Montpellier Cancer Center (ICM: l'Institut du Cancer de Montpellier), and industrial partners. Under the joint supervision of Inserm, the ICM and the University of Montpellier, the IRCM brings together more than 240 people, researchers, clinicians, technicians and students, organized in 16 research teams that rely on high-performance technical platforms and competent support services. In an extremely competitive and rapidly evolving field of research, our greatest challenge is to stay one step ahead. To do so, we will continue to structure cancer research in Montpellier, to seek excellence and to accelerate innovation and transfer to the patient in order to ultimately contribute to overcoming the countless different forms of cancer. Together, let's push the limits"

Nathalie Bonnefoy, Director of the IRCM

MAIN PUBLICATIONS

Tabet I, Candiello E, Fenou L, Velazquez C, Jacot W, Ribeyre C, Sardet C, Theillet C Replication poison treated BRCA1-deficient breast cancers are prone to MRE11 over-resection resulting in single strand DNA accumulation and mitotic catastrophe.. Cancer Research. 2025;in press.

Di Michele M, Attina A, Roux P-F, Laguesse S, Florido J, Houdeville M, Choquet A, Encislai B, Arena G, De Blasio C, Wendling O, Frenois F-X, Papon L, Stuani L, Fuentes M, Jahannault Talignani C, Rousseau M, Guégan J, Buscail Y, Dupré P, Michaud H-A, Rodier G, Bellvert F, Kulyk H, Ferraro Peyret C, Mathieu H, Close P, Rapino F, Chaveroux C, Pirot N, Rubio L, Torro A, Sorg T, Ango F, Hirtz C, Compan V, Lebigot E, Legati A, Ghezzi D, Nguyen L, David A, Sardet C, Lacroix M, Le Cam L E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development. Nat Commun. 2025;16(1):67. doi:10.1038/s41467-024-55444-y

Slaninová V, Heron-Milhavet L, Robin M, Jeanson L, Aissanou A, Kantar D, Tosi D, Bréhélin L, Gongora C, Djiane A The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells. BMC Cancer. 2024;24(1):587. doi:10.1186/s12885-024-12316-4

Bruciamacchie M, Garambois V, Vie N, Bessede T, Michaud H-A, Gros L, Bonnefoy N, Robin M, Brager D, Bigot K, Evrard A, Pourquier P, Colinge J, Mathonnet M, Belhabib I, Jean C, Bousquet C, Colombo P-E, Jarlier M, Gongora C, Larbouret C ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment. Br J Cancer. 2024-11-29. doi:10.1038/s41416-024-02904-3

Desroys du Roure P, Lajoie L, Mallavialle A, Alcaraz L, Mansouri H, Fenou L, Garambois V, Rubio L, David T, Coenon L, Boissière-Michot F, Chateau M-C, Ngo G, Jarlier M, Villalba M, Martineau P, Laurent-Matha V, Roger P, Guiu S, Chardès T, Gros L, Liaudet-Coopman E A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer. J Immunother Cancer. 2024;12(1):e007135. doi:10.1136/jitc-2023-007135

Manteaux G, Amsel A, Riquier-Morcant B, Prieto Romero J, Gayte L, Fourneaux B, Larroque M, Gruel N, Quignot C, Jacq S, Pomiès P, Sengenes C, Chibon F, Heuillet M, Bellvert F, Watson S, Firmin N, Riscal R, Linares L A metabolic crosstalk between liposarcoma and muscle sustains tumor growth. Nat Commun. 2024;15(1):7940. doi:10.1038/s41467-024-51827-3

Villemin J-P, Bassaganyas L, Pourquier D, Boissière F, Cabello-Aguilar S, Crapez E, Tanos R, Cornillot E, Turtoi A, Colinge J Inferring ligand-receptor cellular networks from bulk and spatial transcriptomic datasets with BulkSignalR. Nucleic Acids Res. 2023-05-05. doi:10.1093/nar/gkad352

Jacquier V, Gitenay D, Fritsch S, Bonnet S, Gy?rffy B, Jalaguier S, Linares L, Cavaillès V, Teyssier C RIP140 inhibits glycolysis-dependent proliferation of breast cancer cells by regulating GLUT3 expression through transcriptional crosstalk between hypoxia induced factor and p53. Cell Mol Life Sci. 2022;79(5):270. doi:10.1007/s00018-022-04277-3

Pisareva E, Mihalovi?ová L, Pastor B, Kudriavtsev A, Mirandola A, Mazard T, Maus U, Ostermann L, Weinmann-Menke J, Neuberger E, Simon P, Thierry A Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA. Genome Med. 2022;14(1):135. doi:10.1186/s13073-022-01125-8

du Manoir S, Delpech H, Orsetti B, Jacot W, Pirot N, Noel J, Colombo P-E, Sardet C, Theillet C In high-grade ovarian carcinoma, platinum-sensitive tumor recurrence and acquired-resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2. J Pathol. 2022;257(3):367-378. doi:10.1002/path.5896

Chiavarina B, Costanza B, Ronca R, Blomme A, Rezzola S, Chiodelli P, Giguelay A, Belthier G, Doumont G, Van Simaeys G, Lacroix S, Yokobori T, Erkhem-Ochir B, Balaguer P, Fabbrizio E, Di Valentin E, Detry O, Jerusalem G, Goldman S, Delvenne P, Bellahcène A, Pannequin J, Castronovo V, Turtoi A Metastatic colorectal cancer cells maintain the TGF? program and use TGFBI to fuel angiogenesis. Theranostics. 2021;11(4):1626-1640. doi:10.7150/thno.51507

Relier S, Ripoll J, Guillorit H, Amalric A, Achour C, Boissière F, Vialaret J, Attina A, Debart F, Choquet A, Macari F, Marchand V, Motorin Y, Samalin E, Vasseur J-J, Pannequin J, Aguilo F, Lopez-Crapez E, Hirtz C, Rivals E, Bastide A, David A FTO-mediated cytoplasmic m⁶A_m demethylation adjusts stem-like properties in colorectal cancer cell. 2021-03-20 00:00:00. doi:10.1038/s41467-021-21758-4

Alcaraz L, Mallavialle A, David T, Derocq D, Delolme F, Dieryckx C, Mollevi C, Boissière-Michot F, Huesgen P, Overall C, Tartare-Deckert S, Jacot W, Chardès T, Guiu S, Roger P, Reinheckel T, Moali C, Liaudet-Coopman E A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment. Theranostics. 2021;11(13):6173-6192. doi:10.7150/thno.58254

Pichard A, Marcatili S, Karam J, Constanzo J, Ladjohounlou R, Courteau A, Jarlier M, Bonnefoy N, Patzke S, Stenberg V, Coopman P, Cartron G, Navarro-Teulon I, Repetto-Llamazares A, Heyerdahl H, Dahle J, Bardiès M, Pouget J-P The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest. Leukemia. 2020;34(5):1315-1328. doi:10.1038/s41375-019-0677-4

Alame M, Cornillot E, Cacheux V, Tosato G, Four M, Oliveira L, Gofflot S, Delvenne P, Turtoi E, Cabello-Aguilar S, Nishiyama M, Turtoi A, Martineau V, Colinge J The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities. Theranostics. 2020;10(10):4383-4394. doi:10.7150/thno.42986

Cissé M, Pyrdziak S, Firmin N, Gayte L, Heuillet M, Bellvert F, Fuentes M, Delpech H, Riscal R, Arena G, Chibon F, Le Gellec S, Maran-Gonzalez A, Chateau M-C, Theillet C, Portais J-C, Le Cam L, Linares L Targeting MDM2-dependent serine metabolism as a therapeutic strategy for liposarcoma. Sci Transl Med. 2020;12(547):eaay2163. doi:10.1126/scitranslmed.aay2163

Ho-Pun-Cheung A, Bazin H, Boissière-Michot F, Mollevi C, Landas E, Bleuse J-P, Chardès T, Prost J-F, Pèlegrin A, Jacot W, Mathis G, Lopez-Crapez E Quantification of HER1, HER2 and HER3 by time-resolved Förster resonance energy transfer in FFPE triple-negative breast cancer samples. Br J Cancer. 2020;122(3):397-404. doi:10.1038/s41416-019-0670-8

Hamyeh M, Bernex F, Larive R, Naldi A, Urbach S, Simony-Lafontaine J, Puech C, Bakhache W, Coopman P, Hendriks W, Freiss G PTPN13 induces cell junction stabilization and inhibits mammary tumor invasiveness. Theranostics. 2020;10(3):1016-1032. doi:10.7150/thno.38537

Bousquet Mur E, Bernardo S, Papon L, Mancini M, Fabbrizio E, Goussard M, Ferrer I, Giry A, Quantin X, Pujol J-L, Calvayrac O, Moll H, Glasson Y, Pirot N, Turtoi A, Cañamero M, Wong K-K, Yarden Y, Casanova E, Soria J-C, Colinge J, Siebel C, Favre G, Paz-Ares L, Maraver A Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma. J Clin Invest. 2020;130(2):612-624. doi:10.1172/JCI126896

Ashraf Y, Mansouri H, Laurent-Matha V, Alcaraz L, Roger P, Guiu S, Derocq D, Robin G, Michaud H-A, Jarlier M, Pugnière M, Robert B, Puel A, Martin L, Landomiel F, Bourquard T, Achour O, Fruitier-Arnaudin I, Pichard A, Deshayes E, Turtoi A, Poupon A, Boissière-Michot F, Pirot N, Bernex F, Jacot W, du Manoir S, Theillet C, Pouget J-P, Navarro-Teulon I, Bonnefoy N, Pèlegrin A, Chardès T, Martineau P, Liaudet-Coopman E Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies. J Immunother Cancer. 2019;7(1):29. doi:10.1186/s40425-019-0498-z

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Who are we ?

Located in the Parc Euromédecine, the Institut de Recherche en Cancérologie de Montpellier (U1194) is located on the Val d'Aurelle Campus (ICM, Institut régional du Cancer Montpellier/ Val d'Aurelle).

U1194 Research Centre supported by Inserm, the University of Montpellier and the Institut du Cancer de Montpellier (ICM)

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