Team leader: Antoine Muchir
Striated muscles comprise approximately 40% of total body weight, contain 50–75% of all body proteins and contribute significantly to multiple bodily functions. Two types of striated muscles exist: skeletal and cardiac muscles. They share a common architecture characterized by a very particular and well-described arrangement of muscle cells and associated connective tissue.
Muscular dystrophies are a family of muscle diseases characterized by weakness and progressive muscle degeneration. At the skeletal muscle level, they are manifested by a decrease of muscle strength (muscular dystrophy), and a lack of mobility of the joints (muscle retractions) that begin in childhood or in young adults. In a few cases, the decrease in muscle strength results in a loss of independent walking, making it necessary to use an electric wheelchair to move. These are genetically inherited diseases. There are several forms that differ in the age of onset of symptoms, the nature of the affected muscles, and 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 represents the main cause of death and the severity of these diseases. There is still no cure so far.
Our group is particularly interested in studying the molecular and cellular mechanisms involved in muscular dystrophies and cardiomyopathies. It seems important and necessary to increase our knowledge on the pathophysiology of these pathologies to unveil the cellular / molecular mechanisms that will make it possible to target future therapeutic approaches. We study in vitro and in vivo models of these pathologies and we develop new pharmacological therapies based on our findings.
Antoine MUCHIR CR INSERM, Team Leader
(google scholar : https://scholar.google.fr/citations?user=o2t5Nr0AAAAJ&hl=fr)
(ORCID : https://orcid.org/0000-0002-4780-9275)
Nicolas VIGNIER CR AIM
Cécile PECATTE IE AIM
Stéphanie Bauché IR SU
Nicolas ROSE PhD student
Deborah CARDOSO PhD student
Lorenzo GIORDANI Post-doc Fellow
Caroline LE DOUR Post-doc Fellow
- Vignier N, Chatzifrangkeskou M, Pinton L, Wioland H, Marais T, Lemaitre M, Le Dour C, Peccate C, Cardoso D, Schmitt A, Wu W, Biferi M-G, Naouar N, Macquart C, Beuvin M, Decostre V, Bonne G, Romet-Lemonne G, Worman HJ, Tedesco FS, Jégou A, Muchir A. The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies. Cell Reports. 2021;36:109601.
- Guénantin A-C, Jebeniani I, Leschik J, Watrin E, Bonne G, Vignier N, Pucéat M. Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of laminopathy. J Clin Invest. 2021;131.
- Proietti D, Giordani L, De Bardi M, D’Ercole C, Lozanoska-Ochser B, Amadio S, Volonté C, Marinelli S, Muchir A, Bouché M, Borsellino G, Sacco A, Puri PL, Madaro L. Activation of skeletal muscle-resident glial cells upon nerve injury. JCI Insight. 2021;6:e143469.
- Dridi H, Wu W, Reiken SR, Ofer RM, Liu Y, Yuan Q, Sittenfeld L, Kushner J, Muchir A, Worman HJ, Marks AR. Ryanodine receptor remodeling in cardiomyopathy and muscular dystrophy caused by lamin A/C gene mutation. Hum Mol Genet. 2021;29:3919-3934.
- Girardi F, Taleb A, Ebrahimi M, Datye A, Gamage DG, Peccate C, Giordani L, Millay DP, Gilbert PM, Cadot B, Le Grand F. TGFβ signaling curbs cell fusion and muscle regeneration. Nat Commun. 2021;12:750.
- Haroon M, Klein-Nulend J, Bakker A.D, Jin J, Seddiqi H, Offringa C, De Wit G.M.J, Le Grand F, Giordani L, Liu K.J, Knight R.D, Jaspers R.T. Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche. Biophysical J. 2021;120:2665-2678.
- Guilbert SM, Cardoso D, Lévy N, Muchir A, Nissan X. Hutchinson-Gilford progeria syndrome: Rejuvenating old drugs to fight accelerated ageing. Methods. 2021;190:3-12.
- Giordani, L., He, G.J., Negroni, E., Sakai, H., Law, J.Y., Siu, M.M., Wan, R., Tajbakhsh, S., Cheung, T.H., and Le Grand, F. (2019). High-dimensional single-cell cartography reveals novel skeletal muscle resident cell populations. Mol Cell. 2019 May 2;74(3):609-621.e6. doi: 10.1016/j.molcel.2019.02.026. Epub 2019 Mar 25. PMID: 30922843.
- Chatzifrangkeskou, M., Yadin, D., Marais, T., Chardonnet, S., Cohen-Tannoudji, M., Mougenot, N., Schmitt, A., Crasto, S., Di Pasquale, E., Macquart, C., et al. (2018). Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum. Mol. Genet. 27, 3060–3078.
- Rodriguez, B.M., Khouzami, L., Decostre, V., Varnous, S., Pekovic-Vaughan, V., Hutchison, C.J., Pecker, F., Bonne, G., and Muchir, A. (2018). N-acetyl cysteine alleviates oxidative stress and protects mice from dilated cardiomyopathy caused by mutations in nuclear A-type lamins gene. Hum. Mol. Genet. 27, 3353–3360.
- Vignier, N., Chatzifrangkeskou, M., Morales Rodriguez, B., Mericskay, M., Mougenot, N., Wahbi, K., Bonne, G., and Muchir, A. (2018). Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation. Hum. Mol. Genet. 27, 3870–3880.