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We have 2 main aims (graphical abstract):
Aim 1: Integrative analysis of B and T cell subsets, BCR/TCR, and autoAb repertoires in AID. We will deeply phenotype B and T cell subsets in both healthy individuals and AID patients, employing cutting-edge single-cell technologies to map their transcriptomic, proteomic, and epigenetic profiles. This data will be integrated into an immunomics model to better understand the diversity of B/T cell responses across different diseases.
Aim 2: Deciphering myeloid cell responses in target organ homeostasis disruption. Focusing on target organs like the synovial joint, we will explore the interactions between myeloid cells and other immune cells, using advanced techniques including scRNAseq and imaging mass cytometry coupled with systems biology and machine learning. Our goal is to identify myeloid cell subsets and interactions that contribute to disease progression, paving the way for new therapeutic targets.
Our overall objective is to understand disease heterogeneity and identify potential candidates for the development of personalized therapies and innovative strategies targeting tissue homeostasis disruption.
Generation of non-genetically modified, CAR-like, NK cells
Loïs Coënon, Emilie Rigal, Hortense Courot, Caroline Multrier, Sara Zemiti, Jennifer Lambour, Martine Pugnière, Marion de Toledo, Guillaume Bossis, Guillaume Cartron, Bruno Robert, Pierre Martineau, Bénédicte Fauvel, Jessy Presumey, Martin Villalba
J Immunother Cancer 2024 Jul 18;12(7):e009070. doi: 10.1136/jitc-2024-009070.
IMGT/mAb-KG: the knowledge graph for therapeutic monoclonal antibodies
Gaoussou Sanou, Taciana Manso, Konstantin Todorov, Véronique Giudicelli, Patrice Duroux, Sofia Kossida
Front Immunol. 2024, Jun 20:15:1393839. doi: 10.3389/fimmu.2024.1393839.
Inferring ligand-receptor cellular networks from bulk and spatial transcriptomic datasets with BulkSignalR
Jean-Philippe Villemin, Laia Bassaganyas, Didier Pourquier, Florence Boissière, Simon Cabello-Aguilar, Evelyne Crapez, Rita Tanos, Emmanuel Cornillot, Andrei Turtoi, Jacques Colinge
Nucleic Acids Res. 2023 May 5;51(10):4726-4744. doi: 10.1093/nar/gkad352.
Modular response analysis reformulated as a multilinear regression problem
Jean-Pierre Borg, Jacques Colinge, Patrice Ravel
Bioinformatics 2023 Apr 3;39(4):btad166. doi: 10.1093/bioinformatics/btad166.
Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer
Emilia Rabia, Véronique Garambois, Christine Dhommée, Christel Larbouret, Laurie Lajoie, Yoan Buscail, Gabriel Jimenez-Dominguez, Sylvie Choblet-Thery, Emmanuelle Liaudet-Coopman, Martine Cerutti, Marta Jarlier, Patrice Ravel, Laurent Gros, Nelly Pirot, Gilles Thibault, Eugene A Zhukovsky, Pierre-Emmanuel Gérard, André Pèlegrin, Jacques Colinge, Thierry Chardès
Front Immunol. 2023 Apr 20:14:1168444. doi: 10.3389/fimmu.2023.1168444.
g-NK cells from umbilical cord blood are phenotypically and functionally different than g-NK cells from peripheral blood
Fei Gao, Mauricio Campos Mora, Michael Constantinides, Loïs Coenon, Caroline Multrier, Loïc Vaillant, Tianxiang Zhang, Martin Villalba
Oncoimmunology 2023 Nov 22;12(1):2283353. doi: 10.1080/2162402X.2023.2283353.
Spatial mapping of rheumatoid arthritis synovial niches reveals specific macrophage networks associated with response to therapy
Julien De Lima, Marie-Astrid Boutet, Olivier Bortolotti, Laure-Agnès Chépeaux, Yaël Glasson, Anne-Sophie Dumé, Adrien Le Pluart, Alessandra Nerviani, Liliane Fossati-Jimack, Henri-Alexandre Michaud, Jérôme Guicheux, Benoit Le Goff, Costantino Pitzalis, Gabriel Courties, Florence Apparailly, Frederic Blanchard
BioRxiv 2023. Oct. https://doi.org/10.1101/2023.10.20.563040
Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB.
Taciana Manso, Anjana Kushwaha, Nika Abdollahi, Patrice Duroux, Véronique Giudicelli, Sofia Kossida
Front Immunol. 2023, May 5:14:1129323. doi:10.3389/fimmu.2023.1129323.
IMGT® Immunoinformatics Tools for Standardized V-DOMAIN Analysis
Véronique Giudicelli, Patrice Duroux, Maël Rollin, Safa Aouinti, Géraldine Folch, Joumana Jabado-Michaloud, Marie-Paule Lefranc, Sofia Kossida
Methods Mol Biol. 2022:2453:477-531. doi: 10.1007/978-1-0716-2115-8_24.
IMGT® databases, related tools and web resources through three main axes of research and development
Taciana Manso, Géraldine Folch, Véronique Giudicelli, Joumana Jabado-Michaloud, Anjana Kushwaha, Viviane Nguefack Ngoune, Maria Georga, Ariadni Papadaki, Chahrazed Debbagh, Perrine Pégorier, Morgane Bertignac, Saida Hadi-Saljoqi, Imène Chentli, Karima Cherouali, Safa Aouinti, Amar El Hamwi, Alexandre Albani, Merouane Elazami Elhassani, Benjamin Viart, Agathe Goret, Anna Tran, Gaoussou Sanou, Maël Rollin, Patrice Duroux, Sofia Kossida
Nucleic Acids Res. 2022 Jan 7;50(D1):D1262-D1272. doi: 10.1093/nar/gkab1136.
Percolation transitions in compressed SiO2 glasses
A Hasmy, S Ispas, Bernard Hehlen
Nature 2021 Nov;599(7883):62-66. doi: 10.1038/s41586-021-03918-0.
Mitochondrial microRNAs contribute to macrophage immune functions including differentiation, polarization and activation
Isabelle Duroux-Richard, Florence Apparailly, Maroun Khoury
Front Physiol. 2021 Nov 3:12:738140. doi: 10.3389/fphys.2021.738140.
Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis
Maria I Matias, Carmen S Yong, Amir Foroushani, Chloe Goldsmith, Cédric Mongellaz, Erdinc Sezgin, Kandice R Levental, Ali Talebi, Julie Perrault, Anais Rivière, Jonas Dehairs, Océane Delos, Justine Bertand-Michel, Jean-Charles Portais, Madeline Wong, Julien C Marie, Ameeta Kelekar, Sandrina Kinet, Valérie S Zimmermann, Ilya Levental, Laurent Yvan-Charvet, Johannes V Swinnen, Stefan A Muljo, Hector Hernandez-Vargas, Saverio Tardito, Naomi Taylor, Valérie Dardalhon
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‘SMASH’ recommendations for standardised microscopic arthritis scoring of histological sections from inflammatory arthritis animal models
Silvia Hayer, Margriet J Vervoordeldonk, Maria C Denis, Marietta Armaka, Markus Hoffmann, Johan Bäcklund, Kutty Selva Nandakumar, Birgit Niederreiter, Christina Geka, Anita Fischer, Nina Woodworth, Stephan Blüml, George Kollias, Rikard Holmdahl, Florence Apparailly, Marije I Koenders
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Synovial macrophages: from ordinary eaters to extraordinary multitaskers
Nicole Hannemann, Florence Apparailly, Gabriel Courties
Trends Immunol. 2021 May;42(5):368-371. doi: 10.1016/j.it.2021.03.002.
Novel insights into macrophage diversity in rheumatoid arthritis synovium
Marie-Astrid Boutet, Gabriel Courties, Alessandra Nerviani, Benoit Le Goff, Florence Apparailly, Costantino Pitzalis, Frédéric Blanchard
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SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics
Simon Cabello-Aguilar, Mélissa Alame, Fabien Kon-Sun-Tack, Caroline Fau, Matthieu Lacroix, Jacques Colinge
Nucleic Acids Res. 2020 Jun 4;48(10):e55. doi: 10.1093/nar/gkaa183.
The molecular and stromal landscape of salivary duct carcinoma reveals new therapeutic opportunities.
Melissa Alame, Emmanuel Cornillot, Valère Cacheux, Guillaume Tosato, Marion Four, Laura De Oliveira, Stéphanie Gofflot, Philippe Delvenne, Evgenia Turtoi, Simon Cabello-Aguilar, Masahiko Nishiyama, Andrei Turtoi, Valérie Costes-Martineau, Jacques Colinge
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Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells
Chamutal Bornstein, Shir Nevo, Amir Giladi, Noam Kadouri, Marie Pouzolles, François Gerbe, Eyal David, Alice Machado, Anna Chuprin, Beáta Tóth, Ori Goldberg, Shalev Itzkovitz, Naomi Taylor, Philippe Jay, Valérie S Zimmermann, Jakub Abramson, Ido Amit
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Workpackage 2 (WP2) is built on the complementary expertise of 65 clinicians, researchers, engineers and technicians to propose innovative solutions to restore immune homeostasis in patients suffering from autoimmune diseases (AID). Our consortium is developing cutting-edge biotherapies to selectively target the myeloid cells, T and B lymphocytes involved in AID.
Workpackage 3 (WP3) aims to evaluate the efficacy and safety of therapies based on extracellular vesicles, RNA vectors and CAR-engineered cells in different models (organoids, mathematical models, induced or humanized in vivo models). Longitudinal monitoring of the transcriptomic, metabolic and chromatin organization of CAR-engineered cells will allow the identification of modulated target genes and pathways to predict the immune response.
Workpackage 5 (WP5) is focused on addressing three complex diseases (SLE, RA, and Sclerodermia) through cutting-edge and multidisciplinary technologies, integrating insights from genetics, deep immunophenotyping, transcriptomic and epitranscriptomic analyses, large scale quantitative proteomics, and patient exposure to better stratify the patients.
Multiparametric flow cytometry on PBMCs.
B and T cell purifications for:
• RNAseq Total library
• sc RNA seq VDJ library
Analysis:
• Supervized
• Unsupervized
Single-cell profiling of the patient T and B cells.
Oligoclonality of the TCR and BCR repertoire.
Ag-specific B cell sorting for Immune profiling.
Identification of module of co-regulated genes.
Circulating Biomarkers : Large‐scale quantitative clinical proteomics of patient’s serum.
Multiplexed quantification of chemokines and cytokines.
Autoantigen characterization : Characterization of autoantigens bound to AID-derived serum (LES and Sclerodermia).
Epitranscriptomics : Multiplexed RNA-Modifications quantification.
Multi-omics genomic medicine sequencing :
Long Reads DNA
• SNV and SV analysis
• Methlylation profile
• Long Reads transcriptomics
• Differential expression analysis
• Transcript analysis
Integrated OMICS anaylsis for molecular diagnostic stratification and therapeutic prediction.
Laboratoire de Génétique des Maladies Rares et Autoinflammatoires
Patients’s exposure to:
• Air pollution (remote sensor)
• Water pollution
• Soil contaminants
• Biocontaminants (molds, pollen)
• Infections
• Green, gray, blue spaces
• Diet
• Meteorological variables
• Lifestyle (tobacco, alcohol)
• Occupation
• Socio-economic status
• Etc…
Laboratoire de Génétique des Maladies Rares et Autoinflammatoires
Identification of Biomarkers.
Clustering / Stratification of patients in each AID (RA, SLE, Sclerodermia).
Comparative signature, Identification of sub-population for treatment strategy, Define deregulated pathways and new therapeutic target , in-depth analysis of risk factors, prognostic markers and efficacy of therapeutic interventions, Development of new therapeutic strategies.
Bioproduction of cell or cell-derived ATMPs for clinical applications is a critical part of innovative clinical trials to treat auto-immune diseases. It relies on two cardinal features:
1) a specific cell product, genetically engineered, or modified with antibodies, mRNA or complex culture conditions, meeting specifications that can address unmet clinical applications,
2) a GMP-compliant production that ensures that the end product meets preset specifications, including a robust potency test, and that is produced in sterile, traceable and reproducible fashion. We will complement our bioproduction capacity with private and academic partnerships, including partners of the IHU.
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