NICOLAS LEVY
21 Mars 1963 – Marseille – French.
Medical Genetics Department, Timone Children’s Hospital, 13385 Marseille Cedex 5.
04 91 38 77 87 – Fax : 04 91 49 41 94 – E-mail : nicolas.levy(at)ap-hm.fr
Médical Genetics et Fonctionnal Genomics (Inserm UMR_S 910), Faculté de Médecine,13385 Marseille Cedex 5.
04 91 25 71 59 – Fax : 04 91 80 43 19 – E-mail : nicolas.levy(at)univ-amu.fr
Biosketch :Professor of Human and Molecular Genetics, Head of the Hospital Medical Genetics Department (La Timone, Marseille) and the Inserm research unit 910 at the faculty of Medicine in Marseille. In 2009, he was nominated as the director of the French National Institute for Rare Diseases by the Health Ministry, and in February 2012 he created and became the director of the French Foundation for rare diseases.
Specialized in genetics of laminopathies and neuromuscular disorders, his team has provided the scientific community with some achievements in these fields.
After identifying the LMNA mutation causing the premature aging syndrome named Progeria in 2003, Nicolas Lévy’s efforts have been dedicated to the identification of a treatment for rare premature ageing diseases. Pre-clinical explorations showed that a combination of statins and aminobiphosphonates was beneficial in human cells and a mouse model. On these bases, Nicolas Lévy’s group could start a phase II therapeutic trial using these drugs for European children affected with Progeria. His efforts are also oriented towards the development of therapeutic strategies in specific muscular dystrophies. His team could show the preclinical efficacy of exon skipping as well as a mini-gene transfer approach in dysferlinopathies, representing the preclinical bases of future clinical trials based on gene therapy in patients.
A. Positions, Cursus, Honors.
Present occupations :
University Professor – Hospital Practician (Genetics)
Hospital – Assistance Publique Hôpitaux de Marseille – La Timone Children’s Hospital
– Head of the Medical Genetics Department.
University – Faculté de Médecine de Marseille – Research and Teaching
– Professor of Genetics
– Head of the INSERM UMR_S 910 Research laboratory : «Medical Genetics and Medical Genomics»
– Head of the research team « Nuclear matrix and associated disorders » (Inserm UMR_S 910).
National – Director of the Rare diseases foundation (Paris).
I –Medical Carreer
– Resident : hospitals of Marseille 1987
– Post-resident : Institut Gustave Roussy, Hematology department & Onco-Hematology Genetics lab, Villejuif 1991
– Doctorate in Medicine (MD degree), Aix-Marseille University 1992
– Specialization obtained in Medical Biology- Aix-Marseille University 1992
– Assistant Professor in Genetics 1992
– Associate Professor – Hospital Practician – Department of Medical Genetics 1996
– Full Professor – Hospital Practician – Department of Medical Genetics 2003
– Head of the Medical Genetics Department, 2008
II –Scientific and University Career
– Master degree in Genetics – Aix-Marseille University 1991
– Pasteur Institute – course of somatic and molecular Genetics 1991
– Pre-PhD training in Human Genetics – Institut Pasteur/University of ParisVII – 1992
– Specialization in Human Cytogenetics – Aix-Marseille University 1992
– Research fellow at the Baylor College of Medicine, Human and Molecular Genetics, Houston, TX 1997
– Doctorate in Genetics (PhD degree) – Faculty of Sciences, Aix-Marseille University 2000
– Habilitation to lead research programs – Faculty of medicine, Aix-Marseille University 2002
– Head of the research team : Genetics of neuromuscular disorders, Inserm UMR_S 491 2002
– Head of the research team : Genetics of Neuromuscular disorders & Laminopathies, I 2008
– Creation & Direction of the research Unit Inserm UMR_S 910 « Medical Genetics & Functional genomics » 2008
III – Awards and Fellowship grants
– Recipient of the award of the University (médaille d’or) 1991
– Laureate of Post-residency for research 1992
– Fellowship grant from NATO, for one research year at the Baylor College of Medicine 1997
– National Institute for Health (NIH) Fellowship grant – Baylor College of Medicine, Houston, TX 1998
– Cotterman Award from the American Society of Human Genetics (Team Levy for studies on CMT2B1) 2002
– Recipient of the Jean Frezal award (French Society of Human Genetics)for research & developments on Progeria and related diseases 2008
– Grand prix : Sciences & Technologies Festival (For reserach on Progeria and related disorders) 2009
– Grand prix de la recherche « Robert Debré » (For research on rare diseases & Premature aging) 2012
– Prix de la Fondation pour la Recherche Médicale (FRM) (Prix Rose Lamarca de la recherche clinique) 2014
IV – National and International Occupations : Research Institutes, Networks, Societies,…
– Member of the Inserm Scientific Commission « Functional Genomics and Medical Genetics » 2003 – 2007
– Member of the National Committee for Clinical Research : 2005 – 2007
– Member of the Scientific Board of the Sequencing National Center, 2006 – 2010
– Member of the Scientific committee of the « Université de la Méditerranée », 2000 – 2004
– Member of the Scientific committee of the medical faculty of Marseille, 1997-2001 and 2005-2013
– Member of the Scientific Board of the Association Française contre les Myopathies, 2006 – 2009
– Member of the Executive board of the European Society of Human Genetics, 2003 – 2008
– Member of the American Society of Human Genetics, 1997 – present
– Member of the Human and Medical Genetics Society, 2002 – present
– Director of the GIS-Institut of Rare Diseases, 2009 – 2012
– Director of the Rare diseases foundation, 2012 – present
B. SELECTED PUBLICATIONS
1- Cau P, Navarro C, Harhouri K, Roll P, Sigaudy S, Kaspi E, Perrin S, De Sandre-Giovannoli A, Lévy N. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective. Semin Cell Dev Biol. 2014, Mar 28. S1084-9521(14) 00058-5.
2- Blondel S, Jaskowiak AL, Egesipe AL, Le Corf A, Navarro C, Cordette V, Martinat C, Laabi Y, Djabali K, de Sandre-Giovannoli A, Levy N, Peschanski M, Nissan X. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome. Stem Cells Transl Med. 2014, Apr;3(4):510-9.
3- Ozcan D, Derbent M, Seçkin D, Bikmaz YE, Ağildere M, De Sandre-Giovannoli A, Lévy N, Gürakan B. A collodion baby with facial dysmorphism, limb anomalies, pachygyria and genital hypoplasia: a mild form of Neu-laxova syndrome or a new entity? Ann Dermatol. 2013, Nov;25(4):483-8.
4- Navarro CL, Esteves-Vieira V, Courrier S, Boyer A, Duong Nguyen T, Huong LT, Meinke P, Schröder W, Cormier-Daire V, Sznajer Y, Amor DJ, Lagerstedt K, Biervliet M, van den Akker PC, Cau P, Roll P, Lévy N, Badens C, Wehnert M, De Sandre-Giovannoli A. New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update. Eur J Hum Genet. 2013 Oct 30. doi: 10.1038/ejhg.2013.258.
5- Cacciagli P, Sutera-Sardo J, Borges-Correia A, Roux JC, Dorboz I, Desvignes JP, Badens C, Delepine M, Lathrop M, Cau P, Lévy N, Girard N, Sarda P, Boespflug-Tanguy O, Villard L. Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus. Am J Hum Genet. 2013, Sep 5;93(3):579-86.
6- Caruso N, Herberth B, Bartoli M, Puppo F, Dumonceaux J, Zimmermann A, Denadai S, Lebossé M, Roche S, Geng L, Magdinier F, Attarian S, Bernard R, Maina F, Levy N, Helmbacher F. Deregulation of the protocadherin gene FAT1 alters muscle shapes: implications for the pathogenesis of facioscapulohumeral dystrophy. PLoS Genet. 2013 Jun;9(6):e1003550.
7- Böhm J, Chevessier F, Maues De Paula A, Koch C, Attarian S, Feger C, Hantaï D, Laforêt P, Ghorab K, Vallat JM, Fardeau M, Figarella-Branger D, Pouget J, Romero NB, Koch M, Ebel C, Levy N, Krahn M, Eymard B, Bartoli M, Laporte J. Constitutive activation of the calcium sensor STIM1 causes tubular- aggregate myopathy. Am J Hum Genet. 2013 Feb 7;92(2):271-8.
8- Perrin S, Cremer J, Faucher O, Reynes J, Dellamonica P, Micallef J, Solas C, Lacarelle B, Stretti C, Kaspi E, Robaglia-Schlupp A, Tamalet CN, Lévy N, Poizot-Martin I, Cau P, Roll P. HIV Protease Inhibitors Do Not Cause the Accumulation of Prelamin A in PBMCs from Patients Receiving First Line Therapy: The ANRS EP45 « Aging » Study. PLoS One. 2012;7(12):e53035.
9- Nissan X, Blondel S, Navarro C, Maury Y, Denis C, Girard M, Martinat C, De Sandre-Giovannoli A, Levy N, Peschanski M. Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Report 2012 Jul 26;2(1):1-9.
10- Fabre A, Charroux B, Martinez-Vinson C, Roquelaure B, Odul E, Sayar E, Smith H, Colomb V, Andre N, Hugot JP, Goulet O, Lacoste C, Sarles J, Royet J, Levy N, Badens C. SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am J Hum Genet. 2012 Apr 6;90(4):689-92.
11- Lévy N. Development of synergies and partnerships in rare diseases: model of a scientific cooperation foundation. Presse Med. 2012 May;41 Suppl 1:S23-5.
12- Nguyen K, Walrafen P, Bernard R, Attarian S, Chaix C, Vovan C, Renard E, Dufrane N, Pouget J, Vannier A, Bensimon A, Lévy N. Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy. Ann Neurol. 2011 Oct;70(4):627-33.
13- Osorio FG, Navarro CL, Cadiñanos J, López-Mejía IC, Quirós PM, Bartoli C, Rivera J, Tazi J, Guzmán G, Varela I, Depetris D, de Carlos F, Cobo J, Andrés V, De Sandre-Giovannoli A, Freije JM, Lévy N, López-Otín C. Splicing-directed therapy in a new mouse model of human accelerated aging. Science Transl Med. 2011 Oct 26;3(106):106ra107.
14- Dutour A, Roll P, Gaborit B, Courrier S, Alessi MC, Tregouet DA, Angelis F, Robaglia-Schlupp A, Lesavre N, Cau P, Lévy N, Badens C, Morange PE. High prevalence of laminopathies among patients with metabolic syndrome. Hum Mol Genet. 2011 Oct 1;20(19):3779-86.
15- Puente XS, Quesada V, Osorio FG, Cabanillas R, Cadiñanos J, Fraile JM, Ordóñez GR, Puente DA, Gutiérrez-Fernández A, Fanjul-Fernández M, Lévy N, Freije JM, López-Otín C. Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet. 2011 May 13;88(5):650-6.
16- Krahn M, Wein N, Bartoli M, Lostal W, Courrier S, Bourg-Alibert N, Nguyen K, Vial C, Streichenberger N, Labelle V, DePetris D, Pécheux C, Leturcq F, Cau P, Richard I, Lévy N. A naturally occurring human minidysferlin protein repairs sarcolemmal lesions in a mouse model of dysferlinopathy. Science Transl Med. 2010 Sep 22;2(50):50ra69.
17- Wein N, Avril A, Bartoli M, Beley C, Chaouch S, Laforêt P, Behin A, Butler-Browne G, Mouly V, Krahn M, Garcia L and Lévy N Efficient Bypass of Mutations in Dysferlin Deficient Patient Cells by Antisense-Induced Exon Skipping. Human Mutat. 2010, 31: 136-42.
18- Krahn M, Béroud C, Labelle V, Nguyen K, Bernard R, Bassez G, Figarella-Branger D, Fernandez C, Bouvenot J, Richard I, Ollagnon-Roman E, Bevilacqua JA, Salvo E, Attarian S, Chapon F, Pellissier JF, Pouget J, Hammouda el H, Laforêt P, Urtizberea JA, Eymard B, Leturcq F, Lévy N. Analysis of the DYSF mutational spectrum in a large cohort of patients. Hum Mutat. 2009 Feb;30(2):E345-75.
19- Renard D, Fourcade G, Milhaud D, Bessis D, Esteves-Vieira V, Boyer A, Roll P, Bourgeois P, Lévy N, De Sandre-Giovannoli A. Novel LMNA mutation in atypical Werner syndrome presenting with ischemic disease. Stroke 2009 Feb;40(2):e11-4.
20- Varela I, Pereira S, Ugalde AP, Navarro CL, Suárez MF, Cau P, Cadiñanos J, Osorio FG, Foray N, Cobo J, de Carlos F, Lévy N, Freije JM, López-Otín C. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nature Med. 2008 Jul;14(7):767-72.
21- Delague V, Jacquier A, Hamadouche T, Poitelon Y, Baudot C, Boccaccio I, Chouery E, Chaouch M, Kassouri N, Jabbour R, Grid D, Mégarbané A, Haase G, Lévy N. Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. Am J Hum Genet.2007 Jul;81(1):1-16.
22- Navarro, C.L., Cau, P. and Lévy, N. Molecular bases of progeroid syndromes. Hum Mol Genet, 2006, 15 Suppl 2, R151-161.
23- Nguyen, K., Bassez, G., Bernard, R., Krahn, M., Labelle, V., Figarella-Branger, D., Pouget, J., Hammouda el, H., Beroud, C., Urtizberea, A., Eymard, B., Leturcq, F. and Lévy, N. Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies. Hum Mutat, 2005, 26: 165-…
24- Navarro, C.L., Cadinanos, J., De Sandre-Giovannoli, A., Bernard, R., Courrier, S., Boccaccio, I., Boyer, A., Kleijer, W.J., Wagner, A., Giuliano, F., Beemer, F.A., Freije, J.M., Cau, P., Hennekam, R.C., Lopez-Otin, C., Badens, C. and Lévy, N. Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors. Hum Mol Genet, 2005, 14, 1503-1513.
25- Navarro, C.L., De Sandre-Giovannoli, A., Bernard, R., Boccaccio, I., Boyer, A., Genevieve, D., Hadj-Rabia, S., Gaudy-Marqueste, C., Smitt, H.S., Vabres, P., Faivre, L., Verloes, A., Van Essen, T., Flori, E., Hennekam, R., Beemer, F.A., Laurent, N., Le Merrer, M., Cau, P. and Lévy, N. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet, 2004, 13: 2493- 2503.
26- De Sandre-Giovannoli, A., Bernard, R., Cau, P., Navarro, C., Amiel, J., Boccaccio, I., Lyonnet, S., Stewart, C.L., Munnich, A., Le Merrer, M. and Lévy, N. Lamin A truncation in Hutchinson-Gilford progeria. Science, 2003, 300 : 2055.
27- Bonne, G. and Lévy, N. LMNA mutations in atypical Werner’s syndrome (letter). Lancet 2003, 362 : 1585-1586.
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