PhD in 1989; 1989-1990 postdoctoral fellow at Rockefeller University (New York); CNRS-appointment in 1991; Habilitation in 2007; appointment Research Director (DR) in 2008.
I received my PhD in 1989 at the University Paris7 inthe laboratory of Prof. Michel Fardeau (INSERM U153/UA614 CNRS) on the role of the L-type Ca2+ channel in excitation-contraction coupling in skeletal muscle.
Between 1989 and 1990, I was at the Rockefeller University (New York) in the Laboratory of Prof. Gerald M. Edelman in the field of adhesion molecules and their role in myogenic differentiation. I was appointed by the CNRS in1991. Inthe Laboratory of Prof. Fardeau, I worked on pathological models of the neuromuscular system.
I integrated in 1995 the INSERM Unit «Neuroplasticity and Therapeutics» of Dr. Marc Peschanski (INSERM U421). During this period, I decided to explore therapeutic fields such as cell or gene therapy.
In 1997, I joined Dr. Olivier Danos, who just became Scientific Director of the Genethon laboratory starting its transformation into a Research and Development Centre on gene therapy (Genethon/UMR8115 CNRS).
In 2007, I moved my research team, dedicated to the study of physiopathological processes of Duchenne myopathy, to the Institut de Myologie in Paris (UPMC-Inserm-CNRS) with the aim of developing innovative therapeutic strategies based on transfer of genetically modified cells or on gene transfer.
In end of 2012 I move with my research team to the University of Versailles Saint-Quentin and establish a research Unit on the topic of biotherapies for neuromuscular disorders.
Since 2002, I have published about 47 articles and filed 8 patents.
- Goyenvalle, A., Vulin, A., Fougerousse, F., Leturcq, F., Kaplan, J. C., Garcia, L., and Danos, O. (2004). Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306, 1796-1799.
- Benchaouir, R., Meregalli, M., Farini, A., D’Antona, G., Belicchi, M., Goyenvalle, A., Battistelli, M., Bresolin, N., Bottinelli, R., Garcia, L., and Torrente, Y. (2007). Restoration of human dystrophin following transplantation of exon-skipping-engineered DMD patient stem cells into dystrophic mice. Cell Stem Cell 1, 646-657.
- Lorain, S., Gross, D. A., Goyenvalle, A., Danos, O., Davoust, J., and Garcia, L. (2008). Transient immunomodulation allows repeated injections of AAV1 and correction of muscular dystrophy in multiple muscles. Mol Ther 16, 541-547.
- Lorain, S., Peccate, C., Le Hir, M., and Garcia, L. (2010). Exon exchange approach to repair Duchenne dystrophin transcripts. PLoS One 5, e10894.
- Pietri-Rouxel, F., Gentil, C., Vassilopoulos, S., Baas, D., Mouisel, E., Ferry, A., Vignaud, A., Hourde, C., Marty, I., Schaeffer, L., et al. (2010). DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis. Embo J 29, 643-654.
- Francois, V., Klein, A. F., Beley, C., Jollet, A., Lemercier, C., Garcia, L., and Furling, D. (2010). Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs. Nat Struct Mol Biol.
- Fugier, C., Klein, A. F., Hammer, C., Vassilopoulos, S., Ivarsson, Y., Toussaint, A., Tosch, V., Vignaud, A., Ferry, A., Messaddeq, N., et al. (2011). Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med 17, 720-725.
- Bish, L. T., Sleeper, M. M., Forbes, S. C., Wang, B., Reynolds, C., Singletary, G. E., Trafny, D., Morine, K. J., Sanmiguel, J., Cecchini, S., et al. (2011). Long-term Restoration of Cardiac Dystrophin Expression in Golden Retriever Muscular Dystrophy Following rAAV6-mediated Exon Skipping. Mol Ther.
- Denard, J., Beley, C., Kotin, R., Lai-Kuen, R., Blot, S., Leh, H., Asokan, A., Samulski, R. J., Moullier, P., Voit, T., et al. (2012). Human galectin 3 binding protein interacts with recombinant adeno-associated virus type 6. J Virol.
- Gentil, C., Leturcq, F., Ben Yaou, R., Kaplan, J. C., Laforet, P., Penisson-Besnier, I., Espil-Taris, C., Voit, T., Garcia, L., and Pietri-Rouxel, F. (2012). Variable phenotype of del45-55 Becker patients correlated with nNOSmu mislocalization and RYR1 hypernitrosylation. Hum Mol Genet.
ACTIVITIES
Main thematic areas of research:
The main research theme of our research unit is the development of RNA-based therapeutics to treat hereditary neuromuscular disorders. In the past, we have primarily focused on the development of therapeutic strategies for Duchenne muscular dystrophy (DMD), one of the more severe and the most frequent of the genetic diseases of striated muscle. Our primary approach is the development of technologies to rescue mutated gene products by interfering with mRNA processing (exon skipping, exon inclusion and trans-splicing) using either: antisense molecules, such as non-natural nucleotide analogues (1. Tricyclo-DNA chemistry); 2. Engineered small nuclear RNAs (U7 snRNA); 3. Trans-splicing molecules suited for gene/cell therapy approaches. Concurrently with these projects, we study muscle plasticity to better understand the cascade of events leading to muscle wasting, so as to identify means by which dystrophic processes may be opposed. We additionally identified modifiers of disease severity as potential therapeutic targets. We also develop strategies that modulate TGF-beta signaling in skeletal muscle in order to counteract muscle wasting. We explore whether TGF-beta based strategies are suitable adjunct therapies to increase effects of specific RNA-based therapies to treat neuromuscular disorders.
Importantly, gene interference by RNA modulation emerges as a novel medical technology. We develop these RNA-based therapies in the context of neuromuscular syndromes, however, this technology is transferable to a multitude of pathologies including oncologic disorders. In recent years, we developed RNA-based therapeutic strategies for Duchenne muscular dystrophy, limb muscular dystrophies Type IA and Type IB and myotonic dystrophy type 1. In current projects, we develop strategies for Becker muscular dystrophy, Spinal muscular atrophy as well as for the neurodegenerative disorder Huntington disease.
