IGBMC : Institut de la Génétique et de la Biologie Moléculaire et Cellulaire

• Researchers

  Mohamed Karim HNIA

  Jocelyn LAPORTE

• Post-Doctoral Fellowships

  Johann BOHM

  Belinda COWLING

  Manuela D'ALESSANDRO

  Christos GAVRIILIDIS

  Olga KOUTSOPOULOS

  Barbara ROYER ZEMMOUR

  Ursula SCHAFFER

• Phd Students

  Leonela AMOASII

  Ivana PROKIC

  Nasim VASLI

• Engineers & Technicians

  Claire FEGER

  Catherine KOCH

  Christine KRETZ

• Master Students

  Luc MERCIER

• Collaborateur Occasionnel

  Valérie BIANCALANA

Translational medicine & neurogenetics

Pathophysiology of neuromuscular diseases

We study rare and severe neuromuscular disorders caused by mutations in proteins affecting organelles and membrane trafficking. Our principle focus is on three families of proteins that regulate or are regulated by membrane lipids: the phosphoinositide phosphatase myotubularins, the membrane remodelling amphiphysins and the membrane fissioning GTPase dynamins. Both myotubularins and dynamin 2 are mutated in centronuclear myopathies, severe congenital myopathies characterized by mislocalisation of nuclei and in Charcot-Marie-Tooth peripheral neuropathies, suggesting a common mechanism.
While focusing on these genetic diseases, our approaches are multidisciplinary and encompass the identification of the implicated genes by high-throughput sequencing, the study of the molecular and cellular functions of these proteins in cells and in C. elegans, the validation of mammalian disease models, and the use of viral vectors (AAVs) for pathophysiology studies and preclinical therapeutic trials. In parallel, we study the function of these proteins in skeletal muscle under normal and pathological conditions through the development of novel imaging methods (correlative microscopy and in vivo imaging) in close contact with the IGBMC platforms.

Team website

• Current projects

  - Identification of molecular basis for congenital myopathies by next generation sequencing
  - Membrane and organelles trafficking in skeletal muscle under normal and pathological conditions
  - Characterization of faithful animal models for human myopathies
  - Pre-clinical trials in animal models for congenital myopathies

• Collaborations

  - European consortium on myotubular/centronuclear myopathies sponsored by ENMC (J Laporte is co-chairman)
  - A Beggs, Cildren’s Hospital, Boston, USA: “Molecular basis and pathophysiology of congenital myopathies”
  - A Bolino, San Raffaele Institute, Milano, Italy: “Pathophysiology of neuromuscular diseases due to mutations in several myotubularins” (European E-rare grant)
  - NB Romero, B Eymard, Myology Institute and Centre de Référence de Pathologie Neuromusculaire, AP-HP, Paris, France: “Identification of novel genes for congenital myopathies” (Contrat Hospitalier de Recherche Translationnelle to J Laporte)
  - JL Mandel, Genetic diagnosis laboratory, Strasbourg Hospital, France: “Next generation sequencing for disease genes identification and diagnosis”
  - B Payrastre, U563, Toulouse, France: “Roles of the phosphoinositides PtdIns3P, PtdIns(3,5)P2 and PtdIns5P in cell signalling and trafficking; implication in human disease”

• Prizes/Awards

  • Ivana ZIVKOVIC - Best oral presentation prize - Best oral presentation prize at International Myology Congress - 2011
  • Leonela AMOASII - Best oral presentation prize - Journée Campus d'Illkirch - 2011
  • Johann BOHM - Best oral presentation prize - Journée Campus d'Illkirch - 2010
  • Karim HNIA - Best oral presentation prizen at the World Muscle Society congress (Japan) - Elsevier - 2010
  • Belinda COWLING - Best poster presentation prize at the World Muscle Society congress, Switzerland - Elsevier - 2009
  • Johann BOHM - Best poster presentation prize at the World Muscle Society congress, Switzerland - Elsevier - 2009
  • Jocelyn LAPORTE - Pediatric Pathology Research Senior Prize - Association pour l'étude de la pathologie pédiatrique - Assistance Publique des Hôpitaux de Paris - 2009
  • Jocelyn LAPORTE - Scientific Prize - Association LEYLA Karam de lutte contre les maladies orphelines - 2008
  • Jocelyn LAPORTE - Scientific Prize - Comité Alsace de la Fondation pour la Recherche Médicale (FRM) - 2007

• News

  • April 21, 2012 - Major breakthrough for neuromuscular diseases diagnosis
  • Dec. 6, 2010 - Myopathies, Research in progress : the desmine/myotubularine complexe offers new therapeutic hopes

• Publications

  • Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies

    Toussaint A., Cowling B.S., Hnia K., Mohr M., Oldfors A., Schwab Y., Yis U., Maisonobe T., Stojkovic T., Wallgren-Pettersson C., Laugel V., Echaniz-Laguna A., Mandel J.L., Nishino I., Laporte J.

    Acta Neuropathol Feb 2011 ; 121:253-66 .

  • Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and charcot-marie-tooth peripheral neuropathy.

    Koutsopoulos OS, Koch C, Tosch V, Böhm J, North KN, Laporte J.

    PLoS One 2011 ; 6:e27498 .

  • Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy

    Fugier C., Klein A.F., Hammer C., Vassilopoulos S., Ivarsson Y., Toussaint A., Tosch V., Vignaud A., Ferry A., Messaddeq N., Kokunai Y., Tsuburaya R., de la Grange P., Dembele D., Francois V., Precigout G., Boulade-Ladame C., Hummel M.C., de Munain A.L., Sergeant N., Laquerriere A., Thibault C., Deryckere F., Auboeuf D., Garcia L., Zimmermann P., Udd B., Schoser B., Takahashi M.P., Nishino I., Bassez G., Laporte J., Furling D., Charlet-Berguerand N.

    Nat Med Jun 2011 ; 17:720-5 .

  • Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle

    Hnia K., Tronchere H., Tomczak K.K., Amoasii L., Schultz P., Beggs A.H., Payrastre B., Mandel J.L., Laporte J.

    J Clin Invest Jan. 4, 2011 ; 121:70-85 .

  • Primary T-tubule and autophagy defects in the phosphoinositide phosphatase Jumpy/MTMR14 knockout mice muscle.

    Hnia K, Kretz C, Amoasii L, Böhm J, Liu X, Messaddeq N, Qu CK, Laporte J.

    Adv Enzyme Regul Sept. 12, 2011 .

  • T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases

    Al-Qusairi L., Laporte J.

    Skelet Muscle 2011 ; 1:26 .

  • The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans

    Neukomm L.J., Nicot A.S., Kinchen J.M., Almendinger J., Pinto S.M., Zeng S., Doukoumetzidis K., Tronchere H., Payrastre B., Laporte J.F., Hengartner M.O.

    Development May 2011 ; 138:2003-14 .

  • Increased expression of wild-type or a centronuclear myopathy mutant of dynamin 2 in skeletal muscle of adult mice leads to structural defects and muscle weakness.

    Cowling BS, Toussaint A, Amoasii L, Koebel P, Ferry A, Davignon L, Nishino I, Mandel JL, Laporte J.

    Am J Pathol May 2011 ; 178:2224-35 .

  • Adult course in dynamin 2 dominant centronuclear myopathy with neonatal onset

    Melberg A., Kretz C., Kalimo H., Wallgren-Pettersson C., Toussaint A., Bohm J., Stalberg E., Laporte J.

    Neuromuscul Disord Jan 2010 ; 20:53-56 .

  • Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation

    Bohm J., Yis U., Ortac R., Cakmakci H., Kurul S.H., Dirik E., Laporte J.

    Orphanet J Rare Dis 2010 ; 5:35 .

  See all publications=>

• Job opportunities

  • Post-Doc - Equipe J.Laporte (H/F)
  • Stage M2 In Vivo Study And Therapeutic Approaches In Congenital Myopathies (H/F)
  • Stage M2 Next Generation Sequencing For Genetic Diagnosis And Identification Of Novel Genes In Neuromuscular Diseases (H/F)
  • Phd - Equipe J.Laporte (H/F)