Institut NeuroMyoGène
    Laboratoire Physiopathologie et Génétique du Neurone et du Muscle
    CNRS UMR 5261 -INSERM U1315
    Université de Lyon - Université Claude Bernard Lyon 1
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    • 2023
    • 2022
    • 2021
    • 2020
    • 2019
    • 2018
    • 2017
    • 2016

NERVE-MUSCLE INTERACTIONS

The team develops a series of research topics dedicated to striated muscle and neuromuscular junction. The initial work was mainly focused on the study of the regulation of muscle chromatin and gene expression by motor innervation. Our results progressively led us to explore additional fields of muscle biology such as PI3K/mTOR intracellular trafficking and signalling, actin cytoskeleton, energy metabolism, and protein degradation.
Some discoveries and techniques developed by the team have direct implications for the diagnostic or the treatment of neuromuscular disorders. The team hosts clinicians that are involved in research projects aimed at developing innovative biomarkers and understanding the pathophysiology of neuromuscular disorders.

Acetylcholine receptor Chromatin Cytoskeleton Exosomes Histones Gene expression Neuromuscular junction Neuromuscular disordersPI3K/mTOR Signalling Striated muscles
TEAM
  • Laurent SCHAEFFER
    PROFESSOR
  • Edwige BELOTTI
    POST-DOC UCBL1
  • Julien CARRAS
    EPHE student
  • Véronique CHAUVET
    PhD Student
  • Delia CICCIARELLO
    PhD Student
  • Agnes CONJARD-DUPLANY
    INSERM RESEARCHER
  • Laurent COUDERT
    POST-DOC HCL
  • Andréa EMERIT
    RESEARCH ASSISTANT
  • Yann-Gaël GANGLOFF
    CNRS RESEARCHER
  • Emmanuelle GIRARD
    RESEARCH ASSISTANT
  • Clémence GUERRIAU
    RESEARCH ASSISTANT, HCL
  • Arnaud JACQUIER
    POST-DOC HCL UCBL1
  • Nicolas LACOSTE
    RESEARCH ASSISTANT
  • Pascal LEBLANC
    CNRS RESEARCHER
  • Camille LEONCE
    AHU POST-DOC
  • Laetitia MAZELIN
    INSERM RESEARCHER
  • Vincent MONCOLLIN
    INSERM RESEARCHER
  • Sandrine MOURADIAN
    RESEARCH ASSISTANT
  • Peter MULLIGAN
    INSERM RESEARCHER
  • Alexis OSSENI
    POST-DOC HCL UCBL1
  • Flavien PICARD
    PhD Student
  • Delphine PONCET
    MCU-PH HCL UCBL1
  • Valérie RISSON
    RESEARCH ASSISTANT
  • Isabella SCIONTI
    INSERM RESEARCHER
  • Thomas SIMONET
    MCU-PH HCL UCBL1
CLINICIANS
  • Emilien BERNARD
    PH HCL
  • Françoise BOUHOURS
    PH HCL
  • Philippe LATOUR
    PH HCL
  • Rita MENASSA
    PH HCL
  • Laurence MICHEL
    PH HCL
  • Antoine PEGAT
    PH HCL
  • Nathalie STREICHENBERGER
    MCU-PH HCL UCBL1
  • Juliette SVAHN
    PH HCL
  • Carole VUILLEROT
    MCU PH HCL

Projects
Publications
Funding
Directory

PROJECTS

The team develops 3 fundamental research themes and 2 translational research themes:

  • Regulation of muscle gene expression by motor innervation
  • Nucleus/cytoskeleton links in synapse function
  • TGFb/mTOR signaling in muscle
  • Pathophysiological mechanisms of neuromuscular disorders (NMD)
  • Identification of biomarkers in NMD

2005-2015 MAJOR SCIENTIFIC ACHIEVEMENTS

REGULATION OF MUSCLE GENE EXPRESSION BY MOTOR INNERVATION

  • i) Histone Deacetylase 9 participates in the coupling of neuronal activity to muscle chromatin acetylation and gene expression (Méjat et al., 2005).
  • ii) Post synaptic chromatin is under neural control at the neuromuscular junction (Ravel Chapuis et al., 2007).
  • iii) Repression of muscle gene expression by electrical activity is mediated by the transcriptional co-repressor CtBP (Thomas et al., 2015).
  • iv) The histone deacetylase HDAC6 is a new atrogene and a downstream effector of FoxO transcription factors in cellular stress response (Ratti et al., 2015).

NEUROMUSCULAR JUNCTION AND NUCLEI POSITIONING

Nesprins control nuclei position and postsynaptic receptors density in skeletal muscle (Morel et al. 2014).

DECIPHERING THE ROLE OF PI3K/MTOR SIGNALLING IN SKELETAL MUSCLE

  • i) Establishing the interactome of the PI3K signaling pathway (Pilot-Storck et la., 2010).
  • ii) The PH domain containing protein CKIP-1 act downstream of PI3K to link PI3K signalling and actin cytoskeleton to control muscle differentiation (Baas et al., 2012).
  • iii) In adult muscle, mTOR controls both energy metabolism and dystrophin expression (Risson et al., 2009; Romanino et al., 2011).
  • iv) The autophagic receptor NBR1 is regulated by GSK3-dependent phosphorylation and is deregulated in muscle proteinopathies (Nicot et al., 2014).

TRANSLATIONAL ACTIVITIES

  • i) Identification of a new gene responsible for a congenital myasthenic syndrome (Huze et al., 2009).
  • ii) Development of a cell based assay to detect non-conventional antibodies in French myasthenic patients (Devic et al., 2014).

SELECTED PUBLICATIONS
  • Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy-Case Report.
    A. Pegat, N. Streichenberger, N. Lacoste, M. Hermier, R. Menassa, L. Coudert, J. Theuriet, R. Froissart, S. Terrone, F. Bouhour, L. Michel-Calemard, L. Schaeffer and A. Jacquier.
    Genes
    (2022) DOI: 10.3390/genes13122245
  • Immune-Mediated Rippling Muscle Disease Associated With Thymoma and Anti-MURC/Cavin-4 Autoantibodies.
    J. Svahn , L. Coudert , N. Streichenberger, A. Kraut , A. Gravier-Dumonceau-Mazelier, L. Rotard , L. Calemard-Michel, R. Menassa, E. Errazuriz-Cerda, L. Chalabreysse, A. Osseni, C. Vial, L. Jomir, F. Tronc, D. Le Duy, E. Bernard, V. Gache, Y. Couté, V. Jacquemond, L. Schaeffer, P. Leblanc.
    Neurology: Neuroimmunology & Neuroinflammation
    (2023) DOI: 10.1212/NXI.0000000000200068
  • Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation.
    A. Osseni, A. Ravel-Chapuis, E. Belotti, I. Scionti, Y-G. Gangloff, V. Moncollin, L. Mazelin, R. Mounier, P. Leblanc, B. J. Jasmin & L. Schaeffer.
    Nature Communications
    (2022) DOI: 10.1038/s41467-022-34831-3
  • Expanding the phenotypic variability of MORC2 gene mutations: From Charcot-Marie-Tooth disease to late-onset pure motor neuropathy.
    A. Jacquier, S. Ribault, M. Mendes, N. Lacoste, V. Risson, J. Carras, P. Latour, A. Nadaj-Pakleza, T. Stojkovic, L. Schaeffer.
    Human Mutation
    (2022) DOI: 10.1002/humu.24445
  • Severe congenital myasthenic syndromes caused by agrin mutations affecting secretion by motoneurons.
    A. Jacquier · V. Risson · T. Simonet 1,2 · F. Roussange · N. Lacoste · S. Ribault · J. Carras · J. Theuriet · E. Girard · I. Grosjean · L. Le Goff · S. Kröger · J. Meltoranta · S. Bauché · D. Sternberg · E. Fournier· A. Kostera-Pruszczyk ·E. O’Connor · B. Eymard · H. Lochmüller · C. Martinat · L. Schaeffer.
    Acta Neuropathologica
    (2022) doi: 0.1007/s00401-022-02475-8
  • The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways.
    L. Coudert, A. Osseni, Y. G. Gangloff, L. Schaeffer and P. Leblanc.
    BMC Biology
    (2021) doi: 10.1186/s12915-021-01091.
  • HDAC6 regulates microtubule stability and clustering of AChRs at neuromuscular junctions.
    Osseni A, Ravel-Chapuis A, Thomas JL, Gache V, Schaeffer L, Jasmin BJ.
    J Cell Biol
    (2020) doi: 10.1083/jcb/201901099.
  • H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles.
    Belotti E, Lacoste N, Simonet T, Papin C, Padmanabhan K, Scionti I, Gangloff YG, Ramos L, Dalkara D, Hamiche A, Dimitrov S and Schaeffer L.
    Nucleic Acids Research
    (2020) doi: 10.1093/nar/gkaa157.
  • Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models.
    Coudert L, Nonaka T, Bernard E, Hasegawa M, Schaeffer L, Leblanc P
    Cell Mol Life Sci.
    (2019) doi: 10.1007/s00018-019-03059-8.
  • Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis.
    Zhang Q, Duplany A, Moncollin V, Mouradian S, Goillot E, Mazelin L, Gauthier K, Streichenberger N, Angleraux C, Chen J, Ding S, Schaeffer L, Gangloff YG.
    J Cachexia Sarcopenia Muscle
    (2019) 10:35-53. DOI: 10.1002/jcsm.12336.
  • LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription.
    Scionti I, Hayashi S, Mouradian S, Girard E, Esteves de Lima J, Morel V, Simonet T, Wurmser M, Maire P, Ancelin K, Metzger E, Schüle R, Goillot E, Relaix F, Schaeffer L.
    Cell Rep.
    (2017) 18(8):1996-2006.
  • Muscle inactivation of mTOR causes metabolic defects and dystrophin downregulation leading to a severe myopathy.
    Risson V, Mazelin L, Roceri M, Sanchez H, Moncollin V, Corneloup C, Richard-Bulteau H, Vignaud A, Baas D, Defour A, Freyssenet D, Tanti J-F, Le-Marchand-Brustel Y, Ferrier B, Duplany A, Romanino K, Bauché S, Hanta? D, Mueller M, Kozma SC, Thomas G, Rüegg MA, Ferry A, Pende M, Bigard X, Koulmann N, Schaeffer L, Gangloff YG.
    J.Cell.Biol.
    (2009) 187:859-874.
  • Histone Deacetylase 9 participates in the coupling of neuronal activity to muscle chromatin acetylation and gene expression.
    Méjat A, Ramond F, Bassel Duby R, Khochbin S, Olson EN, and Schaeffer L.
    Nature Neurosci
    (2005) 8(3):313-21.

FUNDING

                     

Email

laurent.schaeffer@univ-lyon1.fr

Phone

+33 4 26 68 82 85

Address

Faculté de Médecine
3ème étage, Aile B
8 Avenue Rockefeller
F-69008 Lyon


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