Hadassah Medical Center

Name of institution: Lariboisière Saint-Louis Medical School, Paris, University Paris 7

Name of institution: Lariboisière Saint-Louis Medical University, University of Paris 7

Date: July 4, 1991: Medical Licence Registration at the Medical Council of Paris (n°55778)

Date: Sept. 11, 1997: Medical Licence Registration at the Medical Council of Bas Rhin (n°7429)

Date: July 4, 2001: Medical Licence Registration at the Medical Council of Essonne (n°11445)

Date: July 4, 2005: Board Certification as a Specialist in Medical Genetics.

Degree: Residency (Internship, Interne des Hôpitaux de Paris), rank: 76/270

Specialty

Location/Head of Department

Dates

Pediatrics

Neuilly Hospital, Neuilly, France

Pr. Claude Lejeune

1/10/1982 to 31/03/1983

(full time)

Pediatrics (neonatalogy)

Antoine-Béclère Hospital, Clamart, France

Pr. Jean Claude Gabilan

1/04/1983 to 2/10/1983

(full time)

Neuropediatrics

Kremlin Bicêtre Hospital,Bicêtre, France

Pr. Pierre Landrieu

3/10/1983 to 31/03/1984

(full time)

Neurology

Lariboisière Hospital, Paris, France

Pr. Bernard Pepin

1/04/1984 to 30/09/1984

(full time)

Neuropediatrics

Raymond-Poincaré Hospital, Garches, France

Pr. Annie Barois

1/10/1984 to 31/03/1985

(full time)

Genetics

Necker - Enfants-Malades Hospital, Paris, France

Pr J. Frezal, (Dr Jean Aicardi)

1/04/1985 to 3/11/1985

(full time)

Genetics

Necker - Enfants-Malades Hospital, Paris, France

Pr J. Frezal, (Pr Jean Marie Saudubray)

111/1986 to 31/05/1987

(full time)

Radiology

Necker - Enfants-Malades Hospital, Paris, France

Pr. Azat Thierree

04/1987 to 10/1987

(full time)

Name of institution: Department of Genetics, Necker - Enfants-Malades Hospital, Paris, France

Name of institution: Department of Neurology, Hôpital Civil de Strasbourg, Strasbourg, France

Name of institution: Department of Pediatrics, Sud Francilien Hospital, Evry, France

Name of institution: Department of Genetics, Necker –Enfants Malades Hospital, Paris, France

Name of institution: Medicine Faculty, University of Paris 11, National Education

Rank: Professor of Medical Genetics, University Medical School, University of Paris 11 and Head of the Medical Genetics Unit, Department of Pediatrics, Sud Francilien Hospital, Evry (half time), France

Name of institution: National Institute of Health and Medical Research (Inserm)

Areas of Study: Neurogenetics, identification of the gene responsible for spinal muscular atrophy

Name of institution: National Institute of Health and Medical Research (Inserm)

Areas of Study: Neurogenetics, characterization of the gene responsible for spinal muscular atrophy

Name of institution: Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC)

Areas of Study: Neurogenetics, Generation of mouse models of neuromuscular disorders

Name of institution: National Institute of Health and Medical Research (Inserm)

Areas of Study: Towards a better understanding of pathophysiology and therapeutic research in motor neuron diseases

Position: Head of the Molecular Neurogenetics Laboratory, Inserm and Evry University, E-1993

Name of institution: National Institute of Health and Medical Research (Inserm)

Rank: Research Director, 1^st class (Inserm, 2002-2005) and Contract with the Assistance Publique- Hôpitaux de Paris (2004-2005)

Areas of Study: Towards a better understanding of pathophysiology and therapeutic research in motor neuron diseases

Position: Head of the Molecular Neurogenetics Laboratory, Inserm and Evry University, E-223

Name of institution: Medicine Faculty, University of Paris 11, National Education

Rank: Professor of Medical Genetics, University Medical School, University of Paris 11

Position: Head of the Molecular Neurogenetics Laboratory, INSERM, Evry University, U-798 Head of the Medical Genetics Unit, Sud Francilien Hospital, Evry

Position: Head of the Department of Human Genetics, Hadassah University Hospital

§ 1997-present: Journal of Human Genetic, Editor in Chief: Pr Yusuke Nakamura

§ 30–31 mai 2005. Gis-Institute of Rare Diseases: Research on rare diseases. Groupama Foundation, 75008 Paris, France. Organizing committee: Alain Fischer, Pascale Borensztein and Judith Melki

§ 1999-2001 Member of the Scientific Committee of the National Center of Sequençing

§ 1999 to 2002 - Member of the Scientific Committee of INSERM (Genetics and Development)

§ 1999 to present - Member of the Scientific Committee of the Association Française contre les Myopathies

§ 2002-2005 President of the Scientific Committee of GIS- Rare Diseases Institute

1987-1988 Chrystèle Bilhou-Nabera, co-supervisor: Prof. Munnich, Resident, Master of Human Genetics, University of Paris 6, degree completed

1989-1990 Afif Hentati, M.D., Tunisia, co-supervisor: Prof. Munnich, Master of Human Genetics, University of Paris 6, degree completed, Publications: n° 14

1989-1991 Sonia Abdelhak, co-supervisor: Prof. Munnich, Master of Human Genetics, University of Paris 6, degree completed, Publications: n°8,11,12,13,17,65,66,67

1992-1993 Barbara Paul, Medical student, Munich, Germany, Publications: n°17,67

1993-1994 Sophie Reboullet, Master of Development, degree completed, Publications: n°23,28

1995-1996 Solange Bertrandy, Master, University of Paris 5, degree completed, Publications: n°36,37

1997-1998 Andoni Echaniz-Laguna, M.D., Master of L. Pasteur University, Strasbourg, degree completed, Publications: n°41, 44, 50

2001-2002 Delphine Charvin, Master, University of Paris 6, degree completed, Publications: n°51, 64

1992-1996 Lydie Burglen, Resident, Doctoral fellow in Human Genetics, University of Paris 5, Ph.D. degree completed with honour (1996), Publications: n°22, 23, 28-31,33,34, 35, 40, 46, 68, 69

1998-2001 Tony Frugier, Ph.D. (2001), University of Paris 5, Ph.D. degree completed with honour, Publications: n°2, 42, 43, 47, 48, 82, 83, 84

2001 to 2006 Nouzah Salah, Ph. D. (2007), University of Evry, Ph.D. degree completed with honour, Publications: n°3, 62

2002 to 2007 Jérémie Vitte, Ph. D. (2007), University of Evry, Ph.D. degree completed with honour, Publications: n°3, 56, 64, 65

2003 to 2007 Etienne Mouisel, Ph. D. (2007), University of Evry, Ph.D. degree completed with honour, Publications: n°59, 64

2004 to present - Coralie Fassier, Ph. D. fellow, University of Evry, Publications: n°64, 65

1989-1990 Parag Sheth, M.D., Postdoctoral fellow, New-York, U.S.A., Publications: n°8, 11, 65, 66

1993-1994 Massimo Zeviani, M.D., sabbatical year, Besta Institute, Milan, Italy, Publications: n°23, 28

1992-1997 Suzie Lefebvre, Ph.D., Postdoctoral fellow, McGill University, Canada, Publications: n°22,23,28-31,33,35,36,37,40,68,69

1994-1995 Louis Viollet, M.D., Postdoctoral fellow, Master of Human Genetics, Paris VI University, Publications: n°28,30,31,33,36

1997-1998 Pierre Miniou, Ph.D., Postdoctoral fellow, Publications: n°35,41,42,43

1997-1998 Deborah Bartholdi, M.D., Postdoctoral fellow, Zurich University, Switzerland, Publications: n°41, 70

1998-1999 Danilo Tiziano, M.D., Postdoctoral fellow, Rome University, Publications: n°32,42,43,45,47,58

1999-2003 Carmen Diaz, Ph.D., Postdoctoral fellow, Publications: n°2,43,47,48,51,53,54,55,82,83,84

· Master of Molecular Genetics and Diseases of Development and Oncogenesis, University of Paris 5, (1995-2004)

· European Master: Sciences of life and Health, Universities of Paris 5 and 7, Genetics and Biotherapy (2004 to 2007)

· Third year of Medical School in Genetics. Medical School, University of Paris 11 (2005-2007)

1- MELKI J. Spinal muscular atrophy. Neuromuscular disorders: clinical and Molecular Genetics. Edited by A. Emery. John Wiley and Sons, 1998: 421-429.

2- Panozzo C, FRUGIER T, CIFUENTES-DIAZ C and MELKI J, Spinal Muscular atrophy The metabolic and molecular bases of inherited disease, eight Edition. Edit. C. Scriver, A. Beaudet, W. Sly, D. Valle, B. Childs and B. Vogelstein. McGraw-Hill, New York. 2001, 4:5833-5844.

3- OLASO R, VITTE J, SALAH N and MELKI J. Spinal Muscular Atrophy in 'Molecular mechanisms of muscular dystrophies'. Edited by S J Winder. Landes Bioscience, 2004

4- MELKI J, KAPLAN J, LUCET V, HALLEY L, CLEMEMCEAU S, KAPLAN C, BAULE MS, FREZAL J. Long QT (Romano-Ward) syndrome: further definition of the linkage of the HLA loci. Cytogenet and Cell Genet 1989; 46: 661

5- BLONDET B, DUXSON MJ, HARRIS AJ, MELKI J, GUENET JL, PINCON-RAYMOND M, RIEGER F. Nerve and muscle development in paralysé mutant mice. Developmental Biology 1989; 132: 153-166.

6- PETIT C, MELKI J, LEVILLIERS J, SERVILLE F, WEISSENBACH J and MAROTEAUX P. An interstitial deletion in Xp22.3 in a family with X-linked recessive chondrodysplasie punctate and short stature. Human Genetics 1990; 85: 247-250.

7- JOURNEL H, MELKI J, TURLEAU C, MUNNICH A, de GROUCHY J. Rett phenotype with X/autosome translocation: possible mapping to the short arm of chromosome X. Am J Med Genet 1990; 35: 147.

8- MELKI J, SHETH P, ABDELHAK S, BURLET P, BACHELOT MF, LATHROP M, FREZAL J, MUNNICH A and the French Spinal Muscular Atrophy Investigators. Mapping of Acute (type I) spinal muscular atrophy to chromosome 5q12-q14. Lancet 1990; 336: 271-273.

9- KAPLAN J, GUASCONI G, BONNEAU D, MELKI J, BRIARD ML, MUNNICH A, DUFIER JL and FREZAL J. Usher syndrome type I is not linked to D1S81 (pTHH33): evidence for genetic heterogeneity. Ann Genet 1990; 33: 105-108.

10- MELKI J, BLONDET B, PINCON-RAYMOND M, DREYFUS P, RIEGER F. Generalized molecular defects of the neuromuscular junction in skeletal muscle of the Wobbler mutant mouse. Neurochem Intern 1991; 18: 425-433.

11- SHETH P, ABDELHAK S, BACHELOT MF, BURLET P, MASSET M, FREZAL J, LATHROP GM, MUNNICH A and MELKI J. Linkage analysis in spinal muscular atrophy, by six clocely flanking markers on chromosome 5. Am J Hum Genet 1991; 48: 764-768.

12- MATTEI MG, MELKI J, BACHELOT MF, ABDELHAK S, BURLET P, FREZAL J and MUNNICH A. In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12-q13.3. Cytog. Cell Genet 1991; 57: 112-113.

13- MELKI J, ABDELHAK S, BURLET P, RACLIN V., KAPLAN J., SPIEGEL R., GILGENKANTZ S., PHILIP N., CHAUVET M.L., DUMEZ Y., BRIARD M.L., FREZAL J., MUNNICH A. Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA probes. J Med Genet 1992; 29: 171-174.

14- HENTATI A, LAMY C, MELKI J, MUNNICH A, de RECONDO J. Clinical and genetic heterogeneity of Charcot Marie Tooth disease. Genomics 1992; 12: 155-157.

15- MULLER B, MELKI J, BURLET P, CLERGET-DARPOUX F. Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q. Am J Hum Genet 1992; 50: 892-895.

16- BENEDETTI L, TARDIEU M, MUNNICH A, TURLEAU C, MELKI J. Parental origin of the X chromosomes in Rett's syndrome. Am J Med Genet 1992; 44: 121-122.

17- MELKI J, BURLET P, CLERMONT O, PASCAL F, PAUL B, ABDELHAK S, NAKAMURA Y, WEISSENBACH J, LATHROP M and MUNNICH A. Refined linkage map of chromosome 5 in the region of the spinal muscular atrophy gene. Genomics 1993; 15: 521-524.

18- TOURNIER-LASSERVE E, JOUTEL A, MELKI J, WEISSENBACH J, LATHROP GM, MAS JL, CHABRIAT H, CABANIS EA, BAUDIMONT M, MACIAZEK J, BACH MA, BOUSSER MG. Cerebral autosomal dominant anteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) maps on chromosome 19q12. Nature Genetics 1993; 3: 256-259.

19- HAZAN J, LAMY C, MELKI J^C, MUNNICH A, de RECONDO J and WEISSENBACH J. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14. Nature Genetics 1993; 5: 163-167.

20- BOILEAU C, JOUDEAU G, BABRON MC, COULON M, ALEXANDREJA, SAKAI L, MELKI J, DELORME G, DUBOURG O, BONAITI-PELLIE C, BOURDARIAS JP, JUNIEN C. Autosomal dominant Marfan-like connective-tissue disorder with aortic delation and skeletal anomalies not linked to the fibrillin genes. Am. J. Hum. Genet 1993; 53: 46-54.

21- MERETTE G, BRZUSTOWICZ LM, DANIELS RJ, DAVIES KE, GILLIAM TC, MELKI J, MUNNICH A, PERICAK-VANCE MA, SIDDIQUE T, VOOSEN B, WIRTH B and OTT J. An investigation of genetic heterogeneity and linkage desequilibrium with 161 families with spinal muscular atrophy. Genomics 1994; 21:27-31.

22- CLERMONT O, BURLET P, BURGLEN L, LEFEBVRE S, PASCAL F, McPHERSON J, COHEN D, LE PASLIER D, WEISSENBACH J, LATHROP JM, MUNNICH A and MELKI J^Pi. Use of genetic and physical mapping to locate the spinal muscular atrophy locus between two new highly polymorphic DNA markers. Am. J. Hum. Genet. 1994;54: 687-694.

23- MELKI J, Lefebvre S, Burglen L, Burlet P, Clermont O, Millasseau P, ReboulLet S, Zeviani M, Le Paslier D, Cohen D, Weissenbach J and Munnich A. De novo and inherited deletions in spinal muscular atrophies. Science 1994; 264: 1474-1477

24- Boespflug-Tanguy O, Mimaulp C, MELKI J, Cavagna A, Pham-Dinh D, Dautigny A and the PMD clinical group. Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the Proteolipoprotein locus in sixteen affected families. Am. J. Hum. Genet. 1994. 55:461-467.

25- Des Portes V., Coulpier M., MELKI J. and Dreyfus P.A. Early detection of mouse wobbler mutation: a model of pathological motoneurone death. NeuroReport 1994. 5; 1861-1864

26- SEQUEIROS J., SILVEIRA I., MACIEL P., COUTINHO P., MANIA A., GASPAR C., BURLET P., LOUREIRO L., GUIMARAES J., TANKA H., TAKIYAMA Y., SAKAMOTO H., NISHIZAWA Y., NOMURA Y., SEGAWA M., TSUJI S., MELKI J, MUNNICH A. Genetic linkage studies of Machado-Joseph disease with chromosome 14q STRPs in 16 Portugues-Azorean kindreds. Genomics 1994. 21: 645-648.

27- HAZAN J., FONTAINE B., BRUYN RPM., LAMY C., VAN DEUTEKOM JT., TIME CS., DURR A., MELKI J, LYON-CAEN O, AGID Y., MUNNICH A., PADBERG GW., DE RECONDO J., FRANTS RR., BRICE A., WEISSENBACH J. Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum. Mol. Genet. 1994 3: 1569-1573

28- Lefebvre S., Bürglen L, Reboullet S, Clermont O., Burlet P., Viollet L., Benichou B., Cruaud C., Millasseau P., Zeviani M., Le Paslier D., Frézal J., Cohen D, Weissenbach J, Munnich A. and MELKI J. Identification and characterization of a spinal muscular atrophy determining gene. Cell 1995; 80; 155-165

29- BUSSAGLIA E, CLERMONT O, TIZZANO E, LEFEBVRE S, BÜRGLEN L, CRUAUD C, URTIZBEREA JA,COLOMER J, MUNNICH A, BAIGET M and MELKI J. A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nature Genetics 1995;11: 335-337

30- Bürglen L, Lefebvre S., Clermont O, Burlet P., Viollet L., Cruaud C., Munnich A. and MELKI J. Structure and Organization of the Human Survival Motor Neurone Gene. Genomics 1996; 32: 479-482

31- Burlet P., Bürglen L., Clermont O., Lefebvre S., Viollet L., Munnich A. and MELKI J. Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease. J. Med. Genet. 1996; 33: 281-283

32- BRAHE C, CLERMONT O, ZAPPATA S., TIZIANO F., MELKI J and NERI G. Frameshift mutation in the SMN gene in a severe case of SMA type I. Hum. Mol. Genet. 1996; 5:1971-1976.

33- BÜRGLEN L, AMIEL J., VIOLLET L., LEFEBVRE S., BURLET P., CLERMONT O, RACLIN V, LANDRIEU P., VERLOES A, MUNNICH A. and MELKI J. SMN gene deletion in the arthrogryposis multiplex congenita-spinal muscular atrophy association. J. Cli. Invest. 1996; 98: 1130-1132

34- RACLIN V., SAUGIER P, BURGLEN L, MUNNICH A, and MELKI J. De novo deletions in spinal muscular atrophy: implication for genetic counselling. J. Med. Genet. 1997, 34:86-87

35- BURGLEN L, SEROZ T, MINIOU P, LEFEBVRE S, BURLET P, MUNNICH A, VIEGAS-PEQUIGNOT E, EGLY JM and MELKI J. The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large scale deletions associated with Werdnig-Hoffmann disease. Am. J. Hum. Genet. 1997, 60:72-79.

36- VIOLLET L., BERTRANDY S., BRUNIALTI A., LEFEBVRE S., CLERMONT O., BURLET P., CRUAUD C., GUENET JL., MUNNICH A. and MELKI J. cDNA isolation, expression and chromosomal localization of the the mouse survival motor neurone gene (Smn). Genomics 1997, 40: 185-188.

37- LEFEBVRE S, BURLET P, LIU Q, BERTRANDY S, CLERMONT O, MUNNICH A, DREYFUSS G and MELKI J. Correlation of severity with the SMN protein level in spinal muscular atrophy. Nature Genetics, 1997 16, 265-269

38- NAVON R, KHOSRAVI R, MELKI J , DRUCKER L, FONTAINE B, TURPIN J, N’GUYEN B; FARDEAU M, RONDOT P, BAUMANN N. Juvenile onset spinal muscular atrophy caused by compound heterozygosity for mutations in HEXA gene. Ann. Neurol. 1997 41: 631-8

39- HANASH A. , LEGUERN E, BIROUK N, CLERMONT O., POUGET J, BOUCHE P., MUNNICH A., BRICE A. and MELKI J. SMN Gene Analysis of the Spinal Form of Charcot-Marie-Tooth Disease. J. Med. Genet. 1997, 34: 507-508.

40- LEFEBVRE S, BURGLEN L, FREZAL J, MUNNICH A, MELKI J. The role of the SMN gene in proximal spinal muscular atrophy. Hum Mol Genet 1998;7:1531-6

41- ECHANIZ-LAGUNA A, MINIOU P, BARTHOLDI D, MELKI J. The Promoters of the Survival Motor Neuron Gene (SMN) and Its Copy (SMNc) Share Common Regulatory Elements. Am J Hum Genet 1999 64:1365-1370

42- MINIOU P, TIZIANO D, FRUGIER T, ROBLOT N, LE MEUR M and MELKI J. Gene targeting restricted to mouse striated muscle lineage. Nucl. Ac. Res. 1999, 27:27-31

43- FRUGIER T, TIZIANO F, CIFUENTES-DIAZ C, MINIOU P, ROBLOT N, DIERICH A, LE MEUR M and MELKI J. Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy. Hum. Mol. Genet. 2000. 9: 849-858.

44- BARON-DELAGE S, ABADIE A, ECHANIZ-LAGUNA A, MELKI J, BERETTA L. Interferons and IRF-1 induce expression of the survival motor neuron (SMN) genes. Mol Med. 2000 6:957-68.

45- PUCCIO H, SIMON D, COSSEE M, CRIQUI-FILIPE P, TIZIANO F, MELKI J, HINDELANG C, MATYAS R, RUSTIN P, KOENIG M. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nature Genetics. 2001, 27:181-186.

46- SKORDIS LA, DUNCKLEY MG, BURGLEN L, CAMPBELL L, TALBOT K, PATEL S, MELKI J, DAVIES KE, DUBOWITZ V, MUNTONI F. Characterisation of novel point mutations in the survival motor neuron gene SMN, in three patients with SMA. Hum Genet. 2001 108:356-7.

47- CIFUENTES-DIAZ C., FRUGIER T, TIZIANO FD, LACENE E, ROBLOT N, JOSHI V, MOREAU MH, MELKI J. Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy. J. Cell Biol. 2001 152: 1107-1114

48- CIFUENTES-DIAZ C, NICOLE S, VELASCO ME, BORRA-CEBRIAN C, PANOZZO C, FRUGIER T, MILLET G, ROBLOT N, JOSHI V, MELKI J. Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model. Hum Mol Genet. 2002 11:1439-47.

50- ECHANIZ-LAGUNA A, GUIRAUD-CHAUMEIL C, TRANCHANT C, REEBER A, MELKI J, WARTER JM. Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): a potential susceptibility factor for adult-onset lower motor neuron disease. J Neurol. 2002 249:290-293.

51- CHARVIN D, CIFUENTES-DIAZ C, FONKNECHTEN N, JOSHI V, HAZAN J, MELKI J and S BETUING. Mutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleus. Hum. Mol. Genet 2003 12:71-78.

52- LUQUET S, LOPEZ-SORIANO J, HOLST D, FREDENRICH A, MELKI J, RASSOULZADEGAN M, GRIMALDI PA. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J. 2003 17:2299-301.

53- NICOLE S, DESFORGES B, MILLET G, LESBORDES J, CIFUENTES-DIAZ C, VERTES D, CAO ML, DE BACKER F, LANGUILLE L, ROBLOT N, JOSHI V, GILLIS JM and MELKI J. Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle J Cell Biol. 2003; 161:571-82.

54- HADDAD H, CIFUENTES-DIAZ C, MIROGLIO A, ROBLOT N, JOSHI V AND MELKI J. Riluzole attenuates spinal muscular atrophy disease progression in a mouse model. 2003 Muscle and Nerve 2003 28:432-7

55- LESBORDES J, CIFUENTES-DIAZ C, MIROGLIO A, JOSHI V, BORDET T, KAHN A and MELKI J. Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy Hum Mol. Genet. 2003 12:1233-1239.

57- FERRI A, MELKI J, KATO AC. Progressive and selective degeneration of motoneurons in a mouse model of SMA. Neuroreport. 2004 15:275-280.

59- BILLAT VL, MOUISEL E, ROBLOT N, MELKI J. Inter- and intrastrain variation in mouse critical running speed. J Appl Physiol. 2005 98:1258-63.

60- KLEBE S, AZZEDINE H, DURR A, BASTIEN P, BOUSLAM N, ELLEUCH N, FORLANI S, CHARON C, KOENIG M, MELKI J, BRICE A, STEVANIN G. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3. Brain. 2006 129:1456-62.

61- OLASO R, JOSHI V, FERNANDEZ J, ROBLOT N, COURAGEOT S, BONNEFONT JP, MELKI J. Activation of RNA metabolism-related genes in mouse but not human tissues deficient in SMN. Physiol Genomics. 2006 24:97-104.

62- SALAH-MOHELLIBI N, MILLET G, ANDRE-SCHMUTZ I, DESFORGES B, OLASO R, ROBLOT N, COURAGEOT S, BENSIMON G, CAVAZZANA-CALVO M, MELKI J. Bone marrow transplantation attenuates the myopathic phenotype of a muscular mouse model of spinal muscular atrophy. Stem Cells. 2006 24:2723-32

63- CHARVET C, HOUBRON C, PARLAKIAN A, GIORDANI J, LAHOUTE C, BERTRAND A, SOTIROPOULOS A, RENOU L, SCHMITT A, MELKI J, LI Z, DAEGELEN D, TUIL D. New role for serum response factor in postnatal skeletal muscle growth and regeneration via the interleukin 4 and insulin-like growth factor 1 pathways. Mol Cell Biol. 2006 26:6664-74

64. TARRADE A, FASSIER C, COURAGEOT S, CHARVIN D, VITTE J, PERIS L, THOREL A, MOUISEL E, FONKNECHTEN N, ROBLOT N, SEILHEAN D, DIÉRICH A, HAUW JJ and MELKI J.A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol. Genet. 2006 15:3544-58.

65. VITTE J, FASSIER C, TIZIANO FD, DALARD C, SOAVE S, ROBLOT N, BRAHE C, SAUGIER-VEBER P, BONNEFONT JP, MELKI J. Refined Characterization of the Expression and Stability of the SMN Gene Products. Am J Pathol. 2007 Aug 23; [Epub ahead of print]

65- MELKI J, ABDELHAK S, SHETH P, BACHELOT MF, BURLET P, MARCADET A, AICARDI J, BAROIS A, CARRIERE JP, FARDEAU M, FONTAN D, PONSOT G, RICHARDET JM, ANGELINI C, BARBOSA C, FERRIERE G, LANZI G, OTTOLINI A, BABRON MC, COHEN D, HANAUER A, CLERGET-DARPOUX F, LATHROP M, MUNNICH A and FREZAL J. The gene responsible for chronic proximal spinal muscular atrophies of childhood maps to chromosome 5q. Nature 1990; 344: 767-768.

66- ABDELHAK S, MELKI J, BACHELOT MF, BURLET P, SHETH P, FREZAL J and MUNNICH A. A PstI polymorphism at the D5S39 locus. Nuc Acids Res 1990; 18: 5580.

67- BURLET P, ABDELHAK S, PASCAL F, CLERMONT O, PAUL B, MUNNICH A and MELKI J. Trinucleotide repeat polymorphism at the D5S556 locus. Human Molecular Genetics 1993; 2: 1328.

68- CLERMONT O., BURLET P., LEFEBVRE S., BURGLEN L, MUNNICH A. and MELKI J. SMN gene deletions in adult-onset spinal muscular atrophy. Lancet. 1995; 346: 1712-1713

69- BURGLEN L, SPIEGEL R, IGNATIUS J, COBBEN JM, LANDRIEU P, LEFEBVRE S, MUNNICH A and MELKI J. SMN gene deletion in variant of infantile spinal muscular atrophy. The Lancet. 1995 346: 316-317

70- BARTHOLDI D, GONZALEZ H, BORG C and MELKI J. Absence of SMN gene deletion in post-polio syndrome. Neuromuscular Disorders. 2000, 10: 99

71- FREZAL J, KAPLAN J, MELKI J. De la myopathie à la dystrophine et retour. Arch Fr Pediatr 1988; 45: 603-608. (review article, in french)

72- MELKI J, MUNNICH A, FREZAL J. Le gène des amyotrophies spinales est localisé sur le bras long du chromosome 5. Médecine/Sciences 1990; 6: 494-495. (review article, in french)

73- MELKI J. Localisation du gène des amyotrophies spinales par les méthodes de génétique inverse. La Revue du Praticien 1991; 18: 1677-1679. (review article, in french)

74- MELKI J, MUNNICH A, BRIARD ML. Problèmes du diagnostic anténatal des amyotrophies spinales infantiles. Journées Parisiennes de Pédiatrie 1991. Flammarion Médecine/Sciences. 265-268. (review article, in french)

75- AUBOURG P, GILGENKRANTZ H, MELKI J, KAPLAN J. Apports de la biologie moléculaire au diagnostic et au conseil génétique dans certaines affections neuromusculaires de l'enfant. Journées Parisiennes de Pédiatrie 1991. Flammarion Médecine/Sciences. 29-38. (review article, in french)

76- DEGUERRE I, LETURCQ F, RECAN F, MELKI J, BURGLEN L. Génétique dans les maladies neuromusculaire. Journées Parisiennes de Pédiatrie 1993. Flammarion Médecine/Sciences. 129-139. (review article, in french)

77- MELKI J, Lefebvre S, Burglen L, Burlet P, Clermont O, Millasseau P, Reboulet S, Zeviani M, Le Paslier D, Cohen D, Weissenbach J, Munnich A. Délétions héritées et de novo dans les amyotrophies spinales infantiles Médecine/Sciences 1994; 10: 889-891. (review article, in french)

78- Bürglen L, Lefebvre S., Reboullet S, Clermont O., Burlet P., Viollet L., Benichou B., Cruaud C., Millasseau P., Zeviani M., Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A et MELKI J. Identification and caractérisation d’un gène déterminant dans les amyotrophies spinales. Médecine/Sciences 1995; 11:149-151. (review article, in french)

79- MELKI J and MUNNICH A . Molecular Genetics of Spinal Muscular Atrophy. A festschrift for Jean Aicardi. Trends in Child Neurology. 1996; 137-141(invited review)

80- BERTRANDY S., LEFEBVRE S., BURLET P., BÜRGLEN L., CLERMONT O., VIOLLET L., MUNNICH A. et MELKI J. Approche moléculaire d’une dégénerescence du motoneurone spinale: les maladies de Werdnig-Hoffmann et de Kugelberg-Welander. Annales de l’Institut Pasteur 1996, 7: 187-192. (invited review, in french))

81- MELKI J. Spinal muscular atrophy. Current Opinion in Neurology. 1997, 10:381-385. (invited review)

82- CIFUENTES-DIAZ C, FRUGIER T, MELKI J. Spinal muscular atrophy. Semin Pediatr Neurol. 2002 9:145-50. (invited review)

83- NICOLE S, DIAZ CC, FRUGIER T, MELKI J. Spinal muscular atrophy: recent advances and future prospects. Muscle Nerve. 2002 26:4-13. (invited review)

84- FRUGIER T, NICOLE S, CIFUENTES-DIAZ C, MELKI J. The molecular bases of spinal muscular atrophy. Curr Opin Genet Dev. 2002 12:294-8. (invited review)

85- TARRADE A, FASSIER C, MELKI J. Neuropathies périphériques et petites protéines de choc thermique. Med Sci (Paris). 2004 20:1073-1075. (review article, in french)

86- « SMN gene, a gene responsible for spinal muscular atrophy» submitted on october 19th 1995 by l’INSERM accepted in Europe, Japan and U.S.A. Co-inventors: Arnold Munnich and Judith Melki

1990. Chromosomal localization of chronic proximal spinal muscular atrophies in childhood. VII International Congress on Neuromuscular Diseases. september 17, 1990. Munich, Germany. (invited speaker).

1992. Spinal muscular atrophy. Second International Workshop on Human Chromosome 5. may 11-13 1992. Chicago, U.S.A. (invited speaker).

1992. Clinical and molecular genetics of spinal muscular atrophy. European Society of Human Genetics. 24th annual meeting. may 27-31 1992. Elsinore, Denmark. (invited speaker).

1994. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. The VII International Congress on Neuromuscular Diseases. July 10-15 1994. Kyoto, Japan. (invited speaker)

1995. Molecular characterization of the spinal muscular atrophy determining gene. 27th annual meeting of the European Society of Human Genetics. Berlin, Germany. May 23-27 1995. (invited speaker)

1995. Molecular Genetics of spinal muscular atrophy. First meeting of European Neuroscience. Amsterdam, The Netherlands. September 1995 3-7. (invited speaker)

1995. Large deletions involving the survival motor neuron, neuronal apoptosis inhibitory protein genes and markers C212-C272 are specific to Werdnig-Hoffmann disease. American Society of Human Genetics. 45th Meeting. Minneapolis, U.S.A. October 24-28 1995.

1996. Molecular genetics of spinal muscular atrophy. Human Genome Meeting. HUGO. Heidelberg, Germany. march 22-24 1996. (invited speaker)

1997 Spinal Muscular Atrophy: etiology and pathogenesis. XVI World Congress of Neurology. September 14-19 1997. Buenos Aires, Argentina (invited speaker)

1997 Molecular basis of spinal muscular atrophy. Second congress of the European Paediatric Neurology Society. October 8-11 1997. Maastricht, The Netherlands (invited speaker)

1998 Consequences of gene conversion and deletion in spinal muscular atrophy. Human Genome Meeting HGM'98. Turin March 28-30 1998. Italy. (invited speaker)

1998. Molecular Basis of Spinal Muscular Atrophy. Human Genetcis Diseases. Weizmann-Inserm Meeting; Weizmann Institute of Sciences, Rehovot, Israël. 11-13 January 1998 (invited speaker)

1998 Spinal muscular atrophy. IX International Congress on Neuromuscular Diseases. Adelaide, Australia. august 30 to september 4 1998. (Plenary lecture, invited speaker)

2000 Insight into the molecular pathogenesis of spinal muscular atrophy. The molecular biology of muscle development and disease. Asilomar, USA, may 21-26 2000. (invited speaker)

2001 Degenerative process in spinal muscular atrophy. The molecular basis of Neurodegenerative Disease. Keystone Symposia. Steamboat Springs, USA. march 29 to april 3 2001 (invited speaker)..

2002. Spinal Muscular Atrophy. IX International Congress on Neuromuscular Diseases. Vancouver, Canada. July 7-12 2002 (Morning lecture, invited speaker)

2003. Mouse models of spinal muscular atrophy: valuable tools for elucidating pathophysiology and therapeutic strategies Molecular Mechanisms of Neurodegeneration, Milan, Italy, May 2-4, 2003. (Invited speaker)

2003. Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle Molecular Biology of Muscle development and Regeneration, the Banff Centre, Alberta, Canada, may 30 to june 4, 2003 (Selected for oral communication).

2003. Cre-loxP: a valuable system to evaluate potentialities of stem cells in neuromuscular disorders. Basic and Clinical Aspects of Stem Cell Research. Weizmann Institute of Sciences, Rehovot, Israël. June 29 to july 1 2003. (Invited speaker).

2003. Inherited motor neuron diseases. France-Israel Workshop on Medical Molecular Genetics. 13-15 december 2003. Petach Tiqva, Israel. (Invited speaker).

2003 Deletion of murine Smn exon 7 directed to liver leads to embryonic lethality: evidence for a dosage effect of SMN in spinal muscular atrophy (SMA); Am Soc Hum Genet; Los Angeles, USA; November 4-8 2003 (Selected for oral communication)

2004. Spinal muscular atrophy: What is the molecular Basis of neuron loss? Cold Spring Harbor Laboratory, The Banbury Center, march 7-10 2004. (Invited speaker)

2004 Involvement of RNA metabolism-related genes in skeletal muscle but not in spinal cord of SMN deficient mice and identification of biomarkers of disease progression; Neuroscience meeting 2004 (34^th annual meeting) ; Oct 23-27 2004 ; San Diego (CA) USA. (Selected for oral communication)

2004. Mouse models of spinal muscular atrophy. Forum of European Neuroscience 2004. Lisbon, Portugal. july 10-14 2004. (Invited speaker)

2005 The spinal muscular atrophies. World Congress of Neurology 2005, Sydney, Australia Nov. 5-11 2005 (invited speaker to a plenary session)

2005 Role of muscle regeneration in mice deficient for Smn in skeletal muscle. Embo workshop. Abbaye Royale de Fontevraud, France. Sept. 24 -29 2005 (Invited speaker and co-organizer of the workshop with Laurent Schaeffer and Margaret Buckingham)

2006 Motor neuron diseases: pathophysiological aspects and therapeutic approaches. VI International Symposium of Clinical and Molecular Genetics. Roma, Italy, May 19, 2006. (Invited speaker)

2006 Spinal Muscular Atrophy. XI International Congress on Neuromuscular Diseases. Istanbul, Turkey,. 2-7 July 2006 (Plenary session, Invited speaker)

§ 1996 - Fondamental Research Prize of the Fondation pour la Recherche Médicale (Medical Research Foundation), Paris

§ 1999 - Jean Pierre Lecocq Prize of the Academy of Science, Institute of France, Paris

§ 2001 - Francis L.McNaughton Lecturer, University McGill, Montreal, Canada

In parallel to my clinical activity in genetics, my main goal was to elucidate the genetic bases of inherited human neurodegenerative diseases in order to develop new diagnostic tools, improve genetic counseling, understand the disease pathogenesis and develop therapeutic strategies.

1. To elucidate the genetic bases of human inherited neurodegenerative disorders

Through genetic linkage analysis and reverse genetic approach, I have contributed to elucidate the genetic bases of the following diseases:

Phenotype-genotypeCorrelation in SMA and related diseases #29, 32, 35, 46, 69,70

4. Generation and/or characterisation of mouse models of neurodegenerative diseases

The refined characterization of mouse models that we have generated has opened new avenues towards therapeutics including:

- Identification of a first molecule, interferon, able to upregulate the SMA gene and its copy in cell cultures: #44

- First evidence that neurotrophic (cardiotrophin-1) or neuroprotective factors (riluzole) are able to attenuate SMA disease progression in mouse models even after the onset of symptoms #54, 55. These results have led to set up a clinical trial in SMA using riluzole (ongoing trial in France).

Recent reports have revealed that hematopoietic stem cells derived from bone marrow have the capacity to differentiate into or fuse to various cell types including skeletal muscle or neurons. Mouse models of SMA offered the opportunity of testing these properties. We have recently shown that bone marrow transplantation was able to attenuate the myopathic phenotype of a muscular mouse model of spinal muscular atrophy through a biological activity mediated by bone marrow derived stem cells. The Hepatocyte Growth Factor (HGF) represents a highly candidate molecule to mediate this biological activity. #62

Since Sept. 1^st 2005, I am Professor of Medical Genetics of the University of Paris 11 and Head of the Medical Genetics Unit in the Pediatric Department of the Sud Francilien Hospital in Evry (France).

As medical geneticist, I am in charge of the genetic counselling of patients and their families at risk for monogenic disorders, genetic testing and prenatal diagnosis. I see outpatients twice a week, organize day hospital for further investigation and see hospitalized patients suspected for having a genetic disease in Neonate Intensive Care Unit, Pediatrics Unit and Maternity. In addition, I am organizing Genetic meetings with pediatricians and obstetricians to discuss on case reports and prenatal diagnosis.