Dr. Aymeric Ravel-Chapuis

Biography

Dr. Ravel-Chapuis completed his graduate training at the Ecole Normale Supérieure de Lyon (France). His graduate research focused on the role of epigenetic modifications as regulators of gene expression during the development and formation of the neuromuscular junction. Subsequently, he completed a postdoctoral fellowship at the University of Ottawa, studying the involvement of RNA-binding proteins in the debilitating RNA-mediated disorder Myotonic Dystrophy. After his post-doctoral training, he became a research associate, developing new research projects studying cell signaling dysfunction in Myotonic Dystrophy and pharmacological approaches to improve the disease phenotype. Now an Assistant Professor in the School of Pharmaceutical Science, he is pleased to contribute to the implementation of this new school and its undergraduate PharmD program 

Expertise 

• Neuromuscular disorders 
• Post-transcriptional regulations 
• Cell Signaling 
• Novel therapeutic strategies 
• Drug repurposing 

Research Projects

Dr. Ravel-Chapuis' research interests focus on the identification of molecular and cellular mechanisms involved in the etiology of neuromuscular disorders and the development of novel therapeutic strategies for these disorders. 

Over the last several years, Dr. Ravel-Chapuis and his team studied Myotonic Dystrophy type 1 (DM1), a complex neuromuscular disease caused by a trinucleotide expansion. This expansion creates a toxic RNA gain-of-function by deregulating RNA-binding proteins and alternative splicing. Their work has established the involvement of an RNA-binding protein, called Staufen1, in DM1. During this research, they discovered new functions of Staufen1 in healthy and diseased muscle. More specifically, they identified that Staufen1: i) regulates alternative splicing and participates in the pathophysiological mechanism of DM1; ii) is involved in the regulation of cellular stress in DM1; iii) regulates muscle differentiation; and iv) regulates skeletal muscle atrophy.  

Furthermore, they began to examine signaling pathways that may also be affected in DM1, thereby contributing to disease pathogenesis. They found that several intracellular signaling pathways are disrupted in DM1 muscle cells: i) the calcium-calcineurin pathway, which is hyperactivated; and ii) the AMPK pathway that is repressed, modulating the symptoms of the disease. Importantly, their work established that pharmacological AMPK activators and exercise improve the DM1 muscle phenotype. 

Finally, it is now well established that muscle has a significant secretory capacity which could trigger systemic benefits through molecules of the myosecretome, including myokines and circulating muscle-specific miRNAs (myomiRNAs). Current research projects of Dr Ravel-Chapuis and his team investigate the role of the myosecretome in the context of DM1 and neuromuscular disorders. 

Publications

• Misquitta N, Ravel-Chapuis A, Jasmin BJ. Combinatorial treatment with exercise and AICAR potentiates the rescue of myotonic dystrophy type 1 mouse muscles in a sex-specific manner. Hum Mol Genet. 2023; 32(4):551-566. DOI: 10.1093/hmg/ddac222 
• Osseni A, Ravel-Chapuis A, Belotti E, et al. Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation. Nat Commun. 2022; 13(1):7108. DOI: 10.1038/s41467-022-34831-3
• Ravel-Chapuis A, Duchesne E, Jasmin BJ. Pharmacological and exercise-based activation of AMPK as emerging therapies for Myotonic Dystrophy type 1 patients. J Physiol. 2022; 600(14):3249-3264. DOI: 10.1113/JP282725
• Ravel-Chapuis A, Jasmin BJ. Combinatorial therapies for rescuing Myotonic Dystrophy type 1 skeletal muscle defects; Trends Mol Med. 2022; 28(6):439-442. DOI: 10.1016/j.molmed.2022.04.004
• Ravel-Chapuis A, Haghandish A, Daneshvar N, Jasmin BJ, Côté J. A novel CARM1-HuR axis involved in muscle differentiation and plasticity misregulated in spinal muscular atrophy. Hum Mol Genet. 2022; 31(9):1453-1470. DOI: 10.1093/hmg/ddab333
• Crawford Parks TE, Marcellus, K., Péladeau C, Jasmin BJ, Ravel-Chapuis A. Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features. Hum Mol Genet. 2020; 29(13):2185-2199. DOI: 10.1093/hmg/ddaa111
• Osseni A, Ravel-Chapuis A, Thomas JL, Gache V, Schaeffer L, Jasmin BJ. HDAC6 Regulates Microtubule Stability and Clustering of AChRs at Neuromuscular Junctions. J Cell Biol. 2020; 219(8):e201901099. DOI: 10.1083/jcb.201901099
• Ravel-Chapuis A, Al-Rewashdy A, Bélanger G, Jasmin BJ. Pharmacological and physiological activation of AMPK improves the spliceopathy in DM1 mouse muscles. Hum Mol Genet. 2018; 27(19):3361-3376. DOI: 10.1093/hmg/ddy245
• Ravel-Chapuis A, Bélanger G, Côté J, Michel RN, Jasmin BJ. Misregulation of calcium-handling proteins promotes hyperactivation of calcineurin-NFAT signaling in skeletal muscle of DM1 mice. Hum Mol Genet. 2017; 26(12):2192-2206. DOI: 10.1093/hmg/ddx109
• Crawford Parks TE, Ravel-Chapuis A, Bondy-Chorney E, Renaud JM, Côté J, Jasmin BJ. Muscle-specific Expression of the RNA-binding Protein Staufen1 Induces Progressive Skeletal Muscle Atrophy via Regulation of Phosphatase Tensin Homolog. Hum Mol Genet. 2017; 26(10):1821-1838. [PMID: 28369467; DOI: 10.1093/hmg/ddx085] 
• Ravel-Chapuis A, Klein Gunnewiek AK, Bélanger G, Crawford Parks TE, Côté J, Jasmin BJ. Staufen1 Impairs Stress Granule Formation in Skeletal Muscle Cells from Myotonic Dystrophy type 1 Patients. Mol Biol Cell. 2016; 27(11):1728-39. DOI: 10.1091/mbc.E15-06-0356
• Bondy-Chorney E, Crawford Parks TE, Ravel-Chapuis A, et al. Staufen1 Regulates Multiple Alternative Splicing Events either Positively or Negatively in DM1 Indicating Its Role as a Disease Modifier. PLoS Genet. 2016; 12(1):e1005827. DOI: 10.1371/journal.pgen.1005827
• Ravel-Chapuis A, Crawford TE, Blais-Crépeau ML, Bélanger G, Richer CT, Jasmin BJ. The RNA-binding protein Staufen1 impairs myogenic differentiation via a c-myc-dependent mechanism. Mol Biol Cell. 2014; 25(23):3765-78. DOI: 10.1091/mbc.E14-04-0895
• Ravel-Chapuis A, Bélanger G, Yadava RS, et al. The RNA-binding protein Staufen1 is increased in DM1 skeletal muscle and promotes alternative pre-mRNA splicing. J Cell Biol. 2012; 196(6):699-712. DOI: 10.1083/jcb.201108113
• Ravel-Chapuis A, Vandromme M, Thomas JL, Schaeffer L. Post synaptic chromatin is under neural control at the neuromuscular junction. EMBO J. 2007; 26(4):1117-28. DOI: 10.1038/sj.emboj.7601572

Awards and Nominations

Dr. Ravel-Chapuis has received grants and fellowships from the Canadian Institute for Health Research, the Muscular Dystrophy Association, the French Ministry of Research, and the French Muscular Dystrophy Association (AFM-Téléthon).