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
Nicolas ROSE PhD student
Deborah CARDOSO PhD student
Lorenzo GIORDANI Post-doc Fellow
Caroline LE DOUR Post-doc Fellow
- 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.
- 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. Molecular Cell in press.
- Lacour, F., Vezin, E., Bentzinger, C.F., Sincennes, M.-C., Giordani, L., Ferry, A., Mitchell, R., Patel, K., Rudnicki, M.A., Chaboissier, M.-C., et al. (2017). R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways. Cell Rep 18, 2320–2330.
- Le Dour, C., Macquart, C., Sera, F., Homma, S., Bonne, G., Morrow, J.P., Worman, H.J., and Muchir, A. (2017). Decreased WNT/β-catenin signalling contributes to the pathogenesis of dilated cardiomyopathy caused by mutations in the lamin a/C gene. Hum. Mol. Genet. 26, 333–343.
- Parisi, A., Lacour, F., Giordani, L., Colnot, S., Maire, P., and Le Grand, F. (2015). APC is required for muscle stem cell proliferation and skeletal muscle tissue repair. J. Cell Biol. 210, 717–726.
- 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.
- Rudolf, A., Schirwis, E., Giordani, L., Parisi, A., Lepper, C., Taketo, M.M., and Le Grand, F. (2016). β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair. Cell Rep 15, 1277–1290.
- 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.