MUCHIR Lab

Signal pathways and striated muscles

Striated muscles account for about 40% of total body weight, contain 50-75% of the body’s total protein and contribute significantly to multiple body functions. There are two types of striated muscle: skeletal and cardiac muscles. They share a common architecture characterized by a very particular and well described arrangement of muscle cells and associated connective tissues.

Muscular dystrophies correspond to a family of muscle diseases characterized by weakness and progressive muscle degeneration. At the skeletal muscular level, they manifest themselves by a decrease in muscle strength (muscular dystrophy), and a lack of mobilité́ joints (muscle retractions) that begin in childhood or in young adults. The decrease in muscle strength leads, in a few cases, to a loss of independent walking, making it necessary to use a power wheelchair to get around. These are diseases of genetic origin. There are several forms that differ in the age of onset of symptoms, the nature of the muscles affected and their severity. At the cardiac level, the presence of abnormalities is observed at a more or less advanced age, mainly in the form of dilated cardiomyopathy, which is the main cause of death and makes the severity of these diseases. At present, there is no curative treatment available.

Our group is particularly interested in studying the molecular and cellular mechanisms involved in two muscular dystrophies: Duchenne muscular dystrophy and Emery-Dreifuss muscular dystrophy. It appears important and necessary to increase our knowledge of the pathophysiology of muscular dystrophies and cardiomyopathies in order to unveil the cellular/molecular mechanisms that will allow us to target future therapeutic approaches. We are studying in vitro and in vivo models of these pathologies and developing novel pharmacological therapies based on our discoveries.

Our research is based on 3 axes:

  • Tissue organization of striated muscles in health and pathology
  • Signalling pathways regulating the links between structure and function in striated muscles
  • Control of striated muscle gene expression through signalling pathways

Team Muchir
Antoine Muchir

Contacts :

Antoine Muchir

NamePositionEmailORCID

Main publications

  1. Forand, A, Muchir, A, Mougenot, N, Sevoz-Couche, C, Peccate, C, Lemaitre, M et al.. Combined Treatment with Peptide-Conjugated Phosphorodiamidate Morpholino Oligomer-PPMO and AAV-U7 Rescues the Severe DMD Phenotype in Mice. Mol Ther Methods Clin Dev. 2020;17 :695-708. doi: 10.1016/j.omtm.2020.03.011. PubMed PMID:32346547 PubMed Central PMC7177166.
  2. Thomasson, R, Vignier, N, Peccate, C, Mougenot, N, Noirez, P, Muchir, A et al.. Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation. Hum Mol Genet. 2019;28 (13):2237-2244. doi: 10.1093/hmg/ddz056. PubMed PMID:31220270 .
  3. Giordani, L, He, GJ, Negroni, E, Sakai, H, Law, JYC, Siu, MM et al.. High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations. Mol Cell. 2019;74 (3):609-621.e6. doi: 10.1016/j.molcel.2019.02.026. PubMed PMID:30922843 .
  4. Vignier, N, Chatzifrangkeskou, M, Morales Rodriguez, B, Mericskay, M, Mougenot, N, Wahbi, K et al.. Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2018;27 (22):3870-3880. doi: 10.1093/hmg/ddy278. PubMed PMID:30053027 .
  5. Rodriguez, BM, Khouzami, L, Decostre, V, Varnous, S, Pekovic-Vaughan, V, Hutchison, CJ et al.. N-acetyl cysteine alleviates oxidative stress and protects mice from dilated cardiomyopathy caused by mutations in nuclear A-type lamins gene. Hum Mol Genet. 2018;27 (19):3353-3360. doi: 10.1093/hmg/ddy243. PubMed PMID:29982513 .
  6. Macquart, C, Jüttner, R, Morales Rodriguez, B, Le Dour, C, Lefebvre, F, Chatzifrangkeskou, M et al.. Microtubule cytoskeleton regulates Connexin 43 localization and cardiac conduction in cardiomyopathy caused by mutation in A-type lamins gene. Hum Mol Genet. 2019;28 (24):4043-4052. doi: 10.1093/hmg/ddy227. PubMed PMID:29893868 .
  7. Chatzifrangkeskou, M, Yadin, D, Marais, T, Chardonnet, S, Cohen-Tannoudji, M, Mougenot, N et al.. Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2018;27 (17):3060-3078. doi: 10.1093/hmg/ddy215. PubMed PMID:29878125 PubMed Central PMC6097156.
  8. Bernasconi, P, Carboni, N, Ricci, G, Siciliano, G, Politano, L, Maggi, L et al.. Elevated TGF β2 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes. Nucleus. 2018;9 (1):292-304. doi: 10.1080/19491034.2018.1467722. PubMed PMID:29693488 PubMed Central PMC5973167.
  9. Le Dour, C, Macquart, C, Sera, F, Homma, S, Bonne, G, Morrow, JP et al.. Decreased WNT/β-catenin signalling contributes to the pathogenesis of dilated cardiomyopathy caused by mutations in the lamin a/C gene. Hum Mol Genet. 2017;26 (2):333-343. doi: 10.1093/hmg/ddw389. PubMed PMID:28069793 PubMed Central PMC6075603.
  10. Chatzifrangkeskou, M, Le Dour, C, Wu, W, Morrow, JP, Joseph, LC, Beuvin, M et al.. ERK1/2 directly acts on CTGF/CCN2 expression to mediate myocardial fibrosis in cardiomyopathy caused by mutations in the lamin A/C gene. Hum Mol Genet. 2016;25 (11):2220-2233. doi: 10.1093/hmg/ddw090. PubMed PMID:27131347 PubMed Central PMC5081054.

AFM Telethon : innover pour guérir
Agence nationale de la recherche
Congenital Muscular Dystrophy Research
Allomek
Fundacion Andres Marcio

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