Cellular and molecular orchestration in muscle regeneration, during ageing andin pathologies.
The team focuses on molecular and cellular actors involved in human in skeletal muscle regeneration, during ageing and in muscle dystrophies, particularly oculo-pharyngeal muscular dystrophy (OPMD) and Duchenne muscular dystrophy (DMD). Our approaches aim at better understandng RNA metabolism, muscle regeneration, muscle stem cells and fibrosis, in order to develop therapeutic strategies.The team has developed a solid expertise on cellular models (incuding through the MyoLine platform for immortalization taht we have set up) and on xenotransplantation using several immunodeficient mouse models and different types of grafts.
Research projects currently developed in parralel and in synergy within the team :
- Molecular mechanisms involved in OPMD and in muscle ageing
- Cell-to-cell communication during muscle regeneration, muscle ageing and fibrosis
- Development of therapeutic strategies
International associated laboratory (LIA) between France and Brazil:
Another aspect specific to our team is the development of international collaborations. In addition to numerous collaborations established over many years, we have set up an international associated laboratory between INSERM and Sorbonne University on the French side, and FIOCRUZ and the Federal University of Rio-de-Janeiro for the brazilian side. This LIA aims at synergize expertises on skeletal muscle and neuromuscular diseases from the French team and on inflammation from the Brazilian team. This LIA has been renew already once, and has produced 14 common publications, a common patent, long-term exchanges of 3 post-docs, 5 common PhD and many short term exchanges, including invited professors in both countries. A common teaching project is being set up (master and/or PhD), which will focus on innovative biotherapies for skeletal muscle.
- Bensalah, M, Muraine, L, Boulinguiez, A, Giordani, L, Albert, V, Ythier, V et al.. A negative feedback loop between fibroadipogenic progenitors and muscle fibres involving endothelin promotes human muscle fibrosis. J Cachexia Sarcopenia Muscle. 2022;13 (3):1771-1784. doi: 10.1002/jcsm.12974. PubMed PMID:35319169 .
- Narici, M, McPhee, J, Conte, M, Franchi, MV, Mitchell, K, Tagliaferri, S et al.. Age-related alterations in muscle architecture are a signature of sarcopenia: the ultrasound sarcopenia index. J Cachexia Sarcopenia Muscle. 2021;12 (4):973-982. doi: 10.1002/jcsm.12720. PubMed PMID:34060717 PubMed Central PMC8350200.
- Strings-Ufombah, V, Malerba, A, Kao, SC, Harbaran, S, Roth, F, Cappellari, O et al.. BB-301: a silence and replace AAV-based vector for the treatment of oculopharyngeal muscular dystrophy. Mol Ther Nucleic Acids. 2021;24 :67-78. doi: 10.1016/j.omtn.2021.02.017. PubMed PMID:33738139 PubMed Central PMC7940701.
- Bamia, A, Sinane, M, Naït-Saïdi, R, Dhiab, J, Keruzoré, M, Nguyen, PH et al.. Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation. Neurotherapeutics. 2021;18 (2):1137-1150. doi: 10.1007/s13311-020-00992-6. PubMed PMID:33533011 PubMed Central PMC8423950.
- Muraine, L, Bensalah, M, Dhiab, J, Cordova, G, Arandel, L, Marhic, A et al.. Transduction Efficiency of Adeno-Associated Virus Serotypes After Local Injection in Mouse and Human Skeletal Muscle. Hum Gene Ther. 2020;31 (3-4):233-240. doi: 10.1089/hum.2019.173. PubMed PMID:31880951 PubMed Central PMC7047108.
- Bensalah, M, Klein, P, Riederer, I, Chaouch, S, Muraine, L, Savino, W et al.. Combined methods to evaluate human cells in muscle xenografts. PLoS One. 2019;14 (5):e0211522. doi: 10.1371/journal.pone.0211522. PubMed PMID:31048846 PubMed Central PMC6497248.
- Malerba, A, Roth, F, Harish, P, Dhiab, J, Lu-Nguyen, N, Cappellari, O et al.. Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy. Hum Mol Genet. 2019;28 (10):1694-1708. doi: 10.1093/hmg/ddz007. PubMed PMID:30649389 .
- Malerba, A, Klein, P, Bachtarzi, H, Jarmin, SA, Cordova, G, Ferry, A et al.. PABPN1 gene therapy for oculopharyngeal muscular dystrophy. Nat Commun. 2017;8 :14848. doi: 10.1038/ncomms14848. PubMed PMID:28361972 PubMed Central PMC5380963.
- Richard, P, Trollet, C, Stojkovic, T, de Becdelievre, A, Perie, S, Pouget, J et al.. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology. 2017;88 (4):359-365. doi: 10.1212/WNL.0000000000003554. PubMed PMID:28011929 PubMed Central PMC5272966.
- Klein, P, Oloko, M, Roth, F, Montel, V, Malerba, A, Jarmin, S et al.. Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing. Nucleic Acids Res. 2016;44 (22):10929-10945. doi: 10.1093/nar/gkw703. PubMed PMID:27507886 PubMed Central PMC5159528.
- Bigot, A, Duddy, WJ, Ouandaogo, ZG, Negroni, E, Mariot, V, Ghimbovschi, S et al.. Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle. Cell Rep. 2015;13 (6):1172-1182. doi: 10.1016/j.celrep.2015.09.067. PubMed PMID:26526994 .
- Chartier, A, Klein, P, Pierson, S, Barbezier, N, Gidaro, T, Casas, F et al.. Mitochondrial dysfunction reveals the role of mRNA poly(A) tail regulation in oculopharyngeal muscular dystrophy pathogenesis. PLoS Genet. 2015;11 (3):e1005092. doi: 10.1371/journal.pgen.1005092. PubMed PMID:25816335 PubMed Central PMC4376527.
- Vallese, D, Negroni, E, Duguez, S, Ferry, A, Trollet, C, Aamiri, A et al.. The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. Mol Ther. 2013;21 (10):1950-7. doi: 10.1038/mt.2013.186. PubMed PMID:23975040 PubMed Central PMC3808143.
- Périé, S, Trollet, C, Mouly, V, Vanneaux, V, Mamchaoui, K, Bouazza, B et al.. Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a phase I/IIa clinical study. Mol Ther. 2014;22 (1):219-25. doi: 10.1038/mt.2013.155. PubMed PMID:23831596 PubMed Central PMC3978797.
- 2016 – Prize for young investigator from Gondation Bettencourt-Scheller (Pierre Klein)
- 2017 – Prize for best oral presentation Myology Congress 2016 (Pierre Klein)
- 2017 – Prize Louis Forrest from the Chancellery of Paris Universitiés (Pierre Klein). The booklet of the ceremony is available here.
- 2019 – Prize for best poster presentation Meeting Endoplasmic reticulum (Fanny Roth)
- 2019 – Travel prize from SFM (Alexis Boulinguiez)