T3S-1124 - UMR-S 1124
Université de Paris
Campus Saint-Germain-des-Près
45 rue des Saints Pères
75270 Paris Cedex 06

Fax : +33 (0) 1 42 86 38 68

Suzie Lefebvre

INSERM researcher, CR- INSERM
Degeneration and plasticity of the locomotor system

suzie.lefebvre@-Code to remove to avoid SPAM-u-paris.fr
+33 1 42 86 21 53, room H330

Student :

Badih Salman

The research interests of Suzie Lefebvre focus on the nuclear organization of RNA-protein (RNP) particles in motor neuron (MN) diseases. In spinal muscular atrophy (SMA), SMN protein deficiency perturbs the organization of RNPs in the cell nucleus. This is also a hallmark of some adult MN diseases. Using a combination of biochemistry, cell imaging and molecular biology, her goal is to understand why deregulated RNPs cause cell death.

Suzie Lefebvre is a full-time permanent INSERM researcher. She obtained the Bachelor and Master’s degrees in Biochemistry from the Université de Montréal (Canada). She studied the photoreaction center of photosynthetic bacteria for her Master’s research. Her interests then moved from photosynthesis to neurobiology and neurodegenerative diseases. She received a PhD degree in Biochemistry from McGill University (Canada) for her work on the cation-binding properties of neurofilaments. She did two post-doctoral fellowships, one in neurovirology at the Pasteur Institute (Paris) and a second in human genetics at Necker-Enfants Malades Hospital. During the later, she contributed to the identification of the spinal muscular atrophy (SMA) gene SMN1 and its phenotype modifier SMN2 gene. She also showed that SMN protein deficiency leads to the SMA disease. This is when she got interested in the functional organization of the nucleus of the cells. Indeed, SMN deficiency inhibits the localization of components in the nucleus, particularly in nuclear Cajal bodies (CBs). Moreover, her group showed that SMN protein is involved in the CB localization of a subset of components, that protein phosphatase PP1 gamma regulates the CB integrity and that pharmacological agents can act on SMN localization to CBs. These results allowed patenting two novel potential therapeutic strategies in motor neuron diseases. She joined Dr. F. Charbonnier’s team in 2013. Her objective is to decipher in vitro and in vivo the signalling mechanisms that underlie subcellular localization with a therapeutic potential against motor neuron diseases.

Recent Publications

Articles

• Pathogenesis and therapeutic targets in spinal muscular atrophy (SMA).
  Lefebvre S, Sarret C : Arch Pediatr, 2020
• The Small-Molecule Flunarizine in Spinal Muscular Atrophy Patient Fibroblasts Impacts on the Gemin Components of the SMN Complex and TDP43, an RNA-Binding Protein Relevant to Motor Neuron Diseases.
  Sapaly D, Delers P, Coridon J, Salman B, Letourneur F, Dumont F, Lefebvre S : Front Mol Biosci, 2020
• Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy.
  Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S : Sci Rep, 2018
• A new role for the calcineurin/NFAT pathway in neonatal myosin heavy chain expression via the NFATc2/MyoD complex during mouse myogenesis.
  Daou N, Lecolle S, Lefebvre S, della Gaspera B, Charbonnier F, Chanoine C, Armand AS : Development, 2013
• A role for protein phosphatase PP1γ in SMN complex formation and subnuclear localization to Cajal bodies.
  Renvoisé B, Quérol G, Verrier ER, Burlet P, Lefebvre S : J Cell Sci, 2012
• Implication of the SMN complex in the biogenesis and steady state level of the signal recognition particle.
  Piazzon N, Schlotter F, Lefebvre S, Dodré M, Méreau A, Soret J, Besse A, Barkats M, Bordonné R, Branlant C, Massenet S : Nucleic Acids Res, 2012
• The loss of the snoRNP chaperone Nopp140 from Cajal bodies of patient fibroblasts correlates with the severity of spinal muscular atrophy.
  Renvoisé B, Colasse S, Burlet P, Viollet L, Meier UT, Lefebvre S : Hum Mol Genet, 2009
• Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells.
  Renvoisé B, Khoobarry K, Gendron MC, Cibert C, Viollet L, Lefebvre S : J Cell Sci, 2006