Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Our research interests focus on two groups of neuromuscular disorders (NMD): myopathies due to abnormalities of the myomatrix and of the nucleus. The long-term objective of our work is to propose relevant therapeutic options based on our knowledge of the genetic basis and of the underlying pathomechanisms at play in these rare diseases.
Research Project: Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Our team focuses on 2 groups of neuromuscular disorders: myopathies due to the defective myomatrix (collagen VI and other components of the extracellular matrix) and to defects of the myonucleus (Emery-Dreifuss muscular dystrophy and other striated muscle laminopathies due to mutations in the laminA/C gene or genes encoding components of nuclear membrane). These myopathies share some clinical features, notably prominent contractures, and constitute differential diagnosis[in1] .
These disorders are highly heterogeneous, clinically and genetically, and to date no treatment is available. Our previous work led us to identify the involvement of various genetic alterations and to develop tools (cellular and animal models) that are crucial for deciphering pathomechanisms, understanding the molecular defects and unveiling therapeutic targets.
We are still facing several challenges and bottlenecks: 1) a number of patients are still awaiting molecular diagnosis; 2) relevant biomarkers are scarce; 3) functions of the involved proteins and underlying pathomechanisms are still poorly understood … We previously have and continue to tackle several transverse processes (e.g. contractile dysfunction, defective mechanosensing, fibrosis …) using our specific expertise (nuclear envelop, nucleoplasm, extracellular matrix…).
Current research axes:
- Definition of genetic and clinical spectrum and delineation of natural history of these NMDs,
- Development of new tools to validate genetic variants identified through NGS (next generation sequencing),
- Deciphering pathomechanisms that affect skeletal and/or cardiac muscle, with the overall goal of identifying and assessing therapeutic options for these disorders.
Our work is carried out on biological material derived from patients (DNA, RNA cultured cells, or muscle biopsies), and on animal models developed in the team (mouse, zebrafish).
Noyau-MEC ©Astrid Brull
| Name | Position | ORCID |
|---|
- L. Bidou, I. Hatin, N. Pérez, V. Allamand, J.J. Panthier, et al.. Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment.. Gene Therapy, 2004, 11, pp.619-627. ⟨hal-02676851⟩
- Sylvie Besse, Valérie Allamand, Jean-Thomas Vilquin, Zhenlin Li, Christophe Poirier, et al.. Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin α2 chain gene. Neuromuscular Disorders, 2003, 13 (3), pp.216-222. ⟨10.1016/s0960-8966(02)00278-x⟩. ⟨hal-03824380⟩
- Allamand V, Laure Bidou. eLS. Wiley, 1, 2001, ⟨10.1002/9780470015902.a0022433.pub2⟩. ⟨hal-03838522⟩
- A Bosch, I Banchs, A Puig, Gilles Vergnaud, V Allamand, et al.. The EUROGEM map of human chromosome 12.. European Journal of Human Genetics, 1993, 2 (3), pp.226-7. ⟨hal-01160670⟩
- Ketty Schwartz, Catherine Chassagne, Kenneth Boheler. The molecular biology of heart failure. Journal of the American College of Cardiology, 1993, 22 (4), pp.A30-A33. ⟨10.1016/0735-1097(93)90459-E⟩. ⟨hal-04275217⟩
- K Schwartz, Catherine Chassagne, L Carrier, K Boheler. [Left ventricular hypertrophy: molecular aspects].. Archives des Maladies du Coeur et des Vaisseaux, 1993, 86 Spec No 1, pp.73-5. ⟨hal-04275406⟩
- L Carrier, Catherine Chassagne, K Boheler, K Schwartz. [Molecular bases of cardiac aging].. La Presse Médicale, 1992, 21 (26), pp.1196-8. ⟨hal-04275777⟩
- K Boheler, Catherine Chassagne, X Martin, C Wisnewsky, K Schwartz. Cardiac expressions of alpha- and beta-myosin heavy chains and sarcomeric alpha-actins are regulated through transcriptional mechanisms. Results from nuclear run-on assays in isolated rat cardiac nuclei.. Journal of Biological Chemistry, 1992, 267 (18), pp.12979-85. ⟨hal-04275047⟩
- L Carrier, K Boheler, Catherine Chassagne, D de la Bastie, C Wisnewsky, et al.. Expression of the sarcomeric actin isogenes in the rat heart with development and senescence.. Circulation Research, 1992, 70 (5), pp.999-1005. ⟨10.1161/01.res.70.5.999⟩. ⟨hal-04275109⟩
- Catherine Chassagne, Ketty Schwartz. Mapping of mRNA isoforms with an oligonucleotide probe: exonuclease VII compared with endonucleases. Nucleic Acids Research, 1992, 20 (12), pp.3256-3256. ⟨10.1093/nar/20.12.3256⟩. ⟨hal-04275102⟩
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Our last work on the OJRD
A guide to writing systematic reviews of rare disease treatments to generate FAIRcompliant datasets: building a Treatabolome