Denis Furling
CNRS Research director, team leader, director of the CRM
Titles and positions
- Accreditation to supervise research (HDR) – Sorbonne Université, Paris
- PhD Molecular and cellular biology – Université Laval, Québec, Canada
Expertises
- Neuromuscular
- Myotonic Dystrophy
- Expanded CTG/CUG repeats
- In vitro and in vivo models
- Pathophysiology
- Therapy
Presentation
My work is mainly focused on Myotonic Dystrophy type 1 (DM1 or Steinert's disease), one of the most frequent neuromuscular diseases in adults, caused by an abnormal expansion of repeated CTG sequences. The research axes aim to decipher the pathophysiological mechanisms induced by the expression of expanded CTG triplets, and to develop innovative therapeutic approaches for DM1. The general goal of the team is to accelerate translational research for Myotonic Dystrophy.
Main publications
- Furling, D. Cas9 targeting of toxic foci of RNA repeats. Nat Biomed Eng. 2021;5 (2):130-131. doi: 10.1038/s41551-021-00688-y. PubMed PMID:33580228 .
- Moulay, G, Lainé, J, Lemaître, M, Nakamori, M, Nishino, I, Caillol, G et al.. Alternative splicing of clathrin heavy chain contributes to the switch from coated pits to plaques. J Cell Biol. 2020;219 (9):. doi: 10.1083/jcb.201912061. PubMed PMID:32642759 PubMed Central PMC7480091.
- Klein, AF, Varela, MA, Arandel, L, Holland, A, Naouar, N, Arzumanov, A et al.. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J Clin Invest. 2019;129 (11):4739-4744. doi: 10.1172/JCI128205. PubMed PMID:31479430 PubMed Central PMC6819114.
- Arandel, L, Polay Espinoza, M, Matloka, M, Bazinet, A, De Dea Diniz, D, Naouar, N et al.. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds. Dis Model Mech. 2017;10 (4):487-497. doi: 10.1242/dmm.027367. PubMed PMID:28188264 PubMed Central PMC5399563.
- Freyermuth, F, Rau, F, Kokunai, Y, Linke, T, Sellier, C, Nakamori, M et al.. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. Nat Commun. 2016;7 :11067. doi: 10.1038/ncomms11067. PubMed PMID:27063795 PubMed Central PMC4831019.
- Rau, F, Lainé, J, Ramanoudjame, L, Ferry, A, Arandel, L, Delalande, O et al.. Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy. Nat Commun. 2015;6 :7205. doi: 10.1038/ncomms8205. PubMed PMID:26018658 PubMed Central PMC4458869.
- Laurent, FX, Sureau, A, Klein, AF, Trouslard, F, Gasnier, E, Furling, D et al.. New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats. Nucleic Acids Res. 2012;40 (7):3159-71. doi: 10.1093/nar/gkr1228. PubMed PMID:22156369 PubMed Central PMC3326330.
- Fugier, C, Klein, AF, Hammer, C, Vassilopoulos, S, Ivarsson, Y, Toussaint, A et al.. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med. 2011;17 (6):720-5. doi: 10.1038/nm.2374. PubMed PMID:21623381 .
- François, V, Klein, AF, Beley, C, Jollet, A, Lemercier, C, Garcia, L et al.. Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs. Nat Struct Mol Biol. 2011;18 (1):85-7. doi: 10.1038/nsmb.1958. PubMed PMID:21186365 .