Ziv Gan-Or, MD, PhD
Le Dr Ziv Gan-Or, professeur adjoint au Neuro, codirige l鈥檜nit茅 de recherche clinique et il est chef du Groupe de recherche sur les maladies neurod茅g茅n茅ratives. Apr猫s des 茅tudes de m茅decine et un doctorat 脿 l鈥橴niversit茅 de Tel-Aviv, il s鈥檌nt茅resse particuli猫rement aux g猫nes li茅s aux lysosomes et 脿 leur r么le dans la pathogen猫se et la progression de la maladie de Parkinson et d鈥檃utres troubles similaires. Dans le Laboratoire de neurog茅nomique et de m茅decine de pr茅cision qu鈥檌l occupe au Neuro, le Dr Gan-Or et son 茅quipe adoptent des approches multiomiques avanc茅es pour 茅tudier les effets de la g茅n茅tique sur le risque, la progression et la r茅ponse aux m茅dicaments dans les maladies neurod茅g茅n茅ratives. Le laboratoire du Dr Gan-Or s鈥檌nt茅resse tout particuli猫rement 脿 la g茅n茅tique du trouble du comportement en sommeil paradoxal (TCSP) et joue un r么le de premier plan dans le Consortium international de g茅nomique du TCSP, qui dispose de la plus grande cohorte au monde de patients souffrant de ce trouble. Il est fort probable que les personnes qui en sont atteintes d茅veloppent une maladie d茅g茅n茅rative, c鈥檈st-脿-dire la maladie de Parkinson, la d茅mence 脿 corps de Lewy ou l鈥檃trophie multisyst茅matis茅e. En observant le contexte g茅n茅tique du TCSP et sa progression vers l鈥檜ne de ces pathologies, le Dr Gan-Or recherche des voies et des m茅canismes inexplor茅s susceptibles de mener 脿 la mise au point de traitements. Le laboratoire, qui a 茅tabli une cinquantaine de collaborations partout dans le monde, offre un environnement unique, motivant et stimulant pour les stagiaires.
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Yu E, Larivi猫re R, Thomas RA, Liu L, Senkevich K, Rahayel S, Trempe JF, Fon EA, and Gan-Or Z. Identification of novel variants, genes and pathways potentially linked to Parkinson鈥檚 disease using machine learning. Brain, in press. 2023.
Le Guen Y, Luo G, Ambati A, Damotte V, Jansen I, Yu E, Nicolas A, de Rojas I, Leal TP, Miyashita A, Bellenguez C, Lian MM, Parveen K, Park H, Grenier-Boley B, Naito T, K眉莽眉kali F, Talyanski SD, Satake W, Yogeshwar SM, Sempere V, Alvarez V, B Arosio, Belloy ME, Benussi L, Boland A, Borroni B, Bullido MJ, Caffarra P, Clarimon J, Daniele A, Darling D, Debette S, Deleuze JF, Dichgans M, Dufouil C, During E, D眉zel E, Galimberti D, Garcia-Ribas G, Garc铆a-Alberca JM, Garc铆a-Gonz谩lez P, V Giedraitis, Goldhardt O, Graff C, Gr眉nblatt E, Hanon O, Hausner L, Heilmann-Heimbach S, Holstege H, Hort J, Jung YJ, J眉rgen D, Kuulasmaa T, Ling L, van der Lugt A, Masullo C, Mecocci P, Mehrabian S, de Mendon莽a A, Merc猫 B, Mir P, Moebus S, Moreno F, Nacmias B, Nicolas G, Nordestgaard BG, Oksenberg J, G Papenberg, Parnetti L, Pasquier F, Pastor P, O Peters, Pijnenburg YAL, Pi帽ol-Ripoll G, Popp J, Porcel LM, Puerta R, P茅rez-Tur J, I Rainero, Ramakers I, Real LM, Riedel-Heller S, Rodriguez-Rodriguez E, Royo JL, Rujescu D, Scarmeas N, Scheltens P, Scherbaum N, Schneider A, Seripa D, Solfrizzi V, Spalletta G, Squassina A, van Swieten J, S谩nchez-Valle R, Tegos T, Tremolizzo L, Vyhnalek M, Verhey F, Wiltfang J, Zhang J, Williams J, Amouyel P, Jessen F, Kehoe P, Andreassen O, Van Duin C, Tsolaki M, S谩nchez-Juan P, Frikke-Schmidt R, Sleegers K, Toda T, Ingelsson M, Okada Y, Rossi G, Hiltunen M, Gim J, Sims R, Foo JN, van der Flier W, Ikeuchi T, Ramirez A, Matta I, Ruiz A, Gan-Or Z, Lambert JC, Greicius MD and Mignot E. Protective association of HLA-DRB1*04 subtypes in neurodegenerative diseases implicates acetylated Tau PHF6 sequences. Proceedings of the National Academy of Sciences (PNAS). 2023. ,
Rahayel S, Tremblay C, Vo A, Mi拧i膰 B, Leh茅ricy S, Arnulf I, Vidailhet M, Corvol JC, the ICEBERG Study Group, Gagnon JF, Postuma RB, Montplaisir JY, Lewis S, Matar E, Martens KE, Borghammer P, Knudsen K, Hansen AK, Monchi O, Gan-Or Z* and Dagher A* (*equal contribution). Mitochondrial function-associated genes underlie cortical atrophy in prodromal synucleinopathies. Brain. 2023. ,
Parlar SC, Grenn FP, Kim JJ, Blauwendraat C and Gan-Or Z. Classification of GBA1 variants in Parkinson disease; the GBA1-PD browser. Movement Disorders. 2023. 38(3):489-495 ,
Krohn L, Heilbron K, Blauwendraat C, Reynolds RH, Yu E, Senkevich K, Rudakou U, Estiar MA, Gustavsson EK, Brolin K, Ruskey JA, Freeman K, Asayesh F, Chia R, Arnulf I, Hu MTM, Montplaisir JY, Gagnon JF, Desautels A, Dauvilliers Y, Gigli GL, Valente M, Janes F, Bernardini A, H枚gl B, Stefani A, Abubaker I, Sonka K, Kemlink D, Oertel W, Janzen A, Plazzi G, Biscarini F, Antelmi E, Figorilli M, Puligheddu M, Mollenhauer B, Trenkwalder C, Sixel-D枚ring F, Cochen De Cock V, Monaca CC, Heidbreder A, Ferini-Strambi L, Dijkstra F, Viaene M, Abril B, Boeve BF, 23andMe Research Team, Scholz SW, Ryten M, Bandres-Ciga S, Noyce A, Cannon P, Pihlstr酶m L, Nalls MA, Singleton AB, Rouleau GA, Postuma RB and Gan-Or Z. Genome-wide association study of REM sleep behavior disorder identifies novel loci with distinct polygenic and brain expression effects. Nature Communications. 2022. 13(1):7496. ,
Senkevich K, Zorca CE, Dworkind A, Rudakou U, Somerville E, Yu E, Ermolaev A, Nikanorova D, Ahmad J, Ruskey JA, Asayesh F, Spiegelman D, Fahn S, Waters C, Monchi O, Dauvilliers Y, Dupr茅 N, Greenbaum L, Hassin-Baer S, Grenn FP, Chiang MSR, Sardi SP, Vanderperre B, Blauwendraat C, Trempe JF, Fon EA, Durcan TM, Alcalay RN and Gan-Or Z. GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson鈥檚 disease. Brain. 2022. 146(5):1859-1872. ,
Yu E, Ambati A, Andersen MS, Krohn L, Estiar MA, Saini P, Senkevich K, Sosero YL, Sreelatha AAK, Ruskey JA, Asayesh F, Spiegelman D, Toft M, Viken MK, the International Parkinson鈥檚 Disease Genomics Consortium (IPDGC), Sharma M, Blauwendraat C, Pihlstr酶m L, Mignot E and Gan-Or Z. Fine mapping of the HLA locus in Parkinson鈥檚 disease in Europeans. npj Parkinson鈥檚 Disease. 2021. 7(1):84. ,
Estiar MA, Yu E, Haj Salem I, Ross JP, Mufti K, Ak莽imen F, Leveille E, Spiegelman D, Ruskey JA, Asayesh F, Dagher A, Yoon G, Tarnopolsky M, Boycott KM, Dupre N, Dion PA, Suchowersky O, Trempe JF, Rouleau GA and Gan-Or Z. Evidence for non-Mendelian inheritance in spastic paraplegia 7. Movement Disorders. 2021. 36(7):1664-1675. ,
Chia R, Sabir MS, Bandres-Ciga S, Saez-Atienzar S, Reynolds RH, Gustavsson E, Walton RL, Ahmed S, Viollet C, Ding J, Makarious MB, Diez-Fairen M, Portley MK, Shah Z, Abramzon Y, Hernandez DG, Blauwendraat C, Stone DJ, Eicher J, Parkkinen L, Ansorge O, Clark L, Honig LS, Marder K, Lemstra A, St George-Hyslop P, Londos E, Morgan K, Lashley T, Warner TT, Jaunmuktane Z, Galasko D, Santana I, Tienari PT, Myllykangas L, Oinas M, Cairns NJ, Morris JC, Halliday GM, Van Deerlin VM, Trojanowski JQ, Grassano M, Calvo A, Mora G, Canosa A, Floris G, Bohannan RC, Brett F, Gan-Or Z, Geiger JT, Moore A, May P, Kr眉ger R, Goldstein D, Lopez G, Tayebi N, Sidransky E, Norcliffe-Kaufmann L, Palma JA, Kaufmann H, Shakkottai V, Perkins M, Newell KL, Gasser T, Schulte C, Landi F, Salvi E, Cusi D, Masliah E, Kim RC, Caraway CA, Monuki E, Brunetti M, Dawson TM, Rosenthal LS, Albert MS, Pletnikova O, Troncoso JC, Flanagan ME, Mao Q, Bigio EH, Rodr铆guez-Rodr铆guez E, Infante J, Lage C, Gonz谩lez-Aramburu I, Sanchez-Juan P, Ghetti B, Keith J, Black SE, Masellis M, Rogaeva E, Duyckaerts C, Brice A, Lesage S, Xiromerisiou G, Barrett MJ, Tilley BS, Gentleman S, Logroscino G, Serrano GE, Beach TG, McKeith IG, Thomas AJ, Attems J, Morris CM, Palmer L, Love S, Troakes C, Al-Sarraj S, Hodges AK, Aarsland D, Klein G, Kaiser SM, Woltjer R, Pastor P, Bekris LM, Leverenz J, Besser LM, Kuzma A, Renton AE, Goate A, Bennett DA, Scherzer CR, Morris HR, Ferrari R, Albani D, Pickering-Brown S, Faber K, Kukull W, Morenas-Rodriguez E, Lle贸 A, Fortea J, Alcolea D, Clarimon J, Nalls MA, Ferrucci L, Resnick SM, Tanaka T, Foroud TM, Graff-Radford NR, Wszolek ZK, Ferman T, Boeve BF, Hardy JA, Topol E, Torkamani A, Singleton AB, Ryten M, Dickson D, Chi貌 A, Ross OA, Gibbs JR, Dalgard CL, Traynor BJ and Scholz SW. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture. Nature Genetics. 2021. 53(3):294-303. ,
Mufti K, Yu E, Rudakou U, Krohn L, Ruskey JA, Asayesh F, Laurent SB, Spiegelman D, Arnulf I, Hu MTM, Montplaisir JY, Gagnon JF, Desautels A, Dauvilliers Y, Gigli GL, Valente M, Janes F, Bernardini A, H枚gl B, Stefani A, Holzknecht E, Sonka K, Kemlink D, Oertel W, Janzen A, Plazzi G, Antelmi E, Figorilli M, Puligheddu M, Mollenhauer B, Trenkwalder C, Sixel-D枚ring F, Cochen De Cock V, Monaca CC, Heidbreder A, Ferini-Strambi L, Dijkstra F, Viaene M, Abril B, Boeve B, Trempe JF, Rouleau GA, Postuma RB and Gan-Or Z. Novel associations of BST1 and LAMP3 with rapid eye movement sleep behavior disorder. Neurology. 2021. 96(10):e1402-e1412. ,
Rudakou U, Yu E, Krohn L, Ruskey JA, Dauvilliers Y, Spiegelman D, Greenbaum L, Fahn S, Waters CH, Dupr茅 N, Rouleau GA, Hassin-Baer S, Fon EA, Alcalay RN and Gan-Or Z. Targeted sequencing of Parkinson鈥檚 disease loci genes highlights SYT11, FGF20 and other associations. Brain. 2020. 144(2):462-472. ,
Yu E, Rudakov U, Krohn L, Mufti K, Ruskey JA, Asayesh F, Estiar MA, Spiegelman D, Fahn S, Waters CH, Greenbaum L, Espay AJ, Dauvilliers Y, Dupr茅 N, Rouleau GA, Hassin-Baer S, Fon EA, Alcalay RN and Gan-Or Z. Analysis of heterozygous PRKN variants and copy number variations in Parkinson鈥檚 disease. Movement Disorders. 2020. 36(1):178-187. ,
Krohn L, Ruskey JA, Rudakou U, Leveille E, Asayesh F, Hu MTM, Arnulf I, Dauvilliers Y, H枚gl B, Stefani A, Monaca CC, Abril B, Plazzi G, Antelmi E, Ferini-Strambi L, Heidbreder A, Boeve BF, Espay AJ, Cochen De Cock V, Mollenhauer B, Sixel-D枚ring F, Trenkwalder C, Sonka K, Kemlink D, Figorilli M, Puligheddu M, Dijkstra F, Viaene M, Oertel W, Toffoli M, Gigli GL, Valente M, Gagnon JF, Desautels A, Montplaisir JY, Postuma RB, Rouleau GA and Gan-Or Z. GBA variants in REM sleep behavior disorder: a multicenter study. Neurology. 2020. 95(8):e1008-e1016. ,
Leonard H, Blauwendraat C, Krohn L, Faghri F, Iwaki H, Furgeson G, Day-Williams AG, Stone DJ, International Parkinson鈥檚 Disease Genomics Consortium (IPDGC), Singleton AB, Nalls MA and Gan-Or Z. Genetic variability and potential effects on clinical trial outcomes: perspectives in Parkinson鈥檚 disease. Journal of Medical Genetics. 2020. 57:331鈥�338. ,
Krohn L, Wu RYJ, Heilbron K, Ruskey JA, Laurent SB, Blauwendraat C, Alam A, Arnulf I, Hu MTM, Dauvilliers Y, H枚gl B, Toft M, Bj酶rnar氓 KA, Stefani A, Holzknecht E, Monaca CC, Beatriz A, Plazzi G, Antelmi E, Ferini-Strambi L, Young P, Heidbreder A, Cochen De Cock V, Mollenhauer B, Sixel-D枚ring F, Trenkwalder C, Sonka K, Kemlink D, Figorilli M, Puligheddu M, Dijkstra F, Viaene M, Oertel W, Toffoli M, Gigli GL, Valente M, Gagnon JF, Nalls MA, Singleton AB, 23andMe Research Team, Desautels A, Montplaisir JY, Cannon P, Ross OA, Boeve BF, Dupr茅 N, Fon EA, Postuma RB, Pihlstr酶m L, Rouleau GA and Gan-Or Z. Fine-mapping of SNCA in REM sleep behavior disorder and overt synucleinopathies. Annals of Neurology. 2020. 87(4):584-598. ,
Krohn L, 脰zt眉rk TN, Vanderperre B, Ouled Amar Bencheikh B, Ruskey JA, Laurent SB, Spiegelman D, Postuma RB, Arnulf I, Hu MTM, Dauvilliers Y, H枚gl B, Stefani A, Monaca CC, Plazzi G, Antelmi E, Ferini-Strambi L, Heidbreder A, Rudakou U, Cochen De Cock V, Young P, Wolf P, Oliva P, Zhang XK, Greenbaum L, Liong C, Gagnon JF, Desautels A, Hassin-Baer S, Montplaisir JY, Dupr茅 N, Rouleau GA, Fon EA, Trempe JF, Lamoureux G, Alcalay RN and Gan-Or Z. Genetic, structural and functional evidence link TMEM175 to synucleinopathies. Annals of Neurology. 2020. 87(1):139-153.
Blauwendraat C, Reed X, Krohn L, Heilborn K, Bandres-Ciga S, Tan M, Gibbs R, Hernandez DG, Kumaran R, Langston R, Bonet-Ponce L, Alcalay RN, Hassin-Baer S, Greenbaum L, Iwaki H, Leonard H, Grenn FP, Ruskey JA, Sabir M, Ahmed S, Makarious MB, Pihlstr酶m L, Toft M, van Hilten JJ, Marinus J, Schulte C, Brockmann K, Sharma M, Siitonen A, Majamaa K, Eerola-Rautio J, Tienari PJ, Pantelyat A, Hillis-Trupe AE, Dawson TM, Rosenthal LS, Albert MS, Resnick SM, Ferrucci L, Morris CM, Pletnikova O, Troncoso J, Grosset D, Lesage S, Corvol JC, Brice A, Noyce AJ, Masliah E, Wood N, Hardy J, Shulman LM, Jankovic J, Shulman JM, Heutink P, Gasser T, Cannon P, Scholz SW, Morris H, Cookson M, Nalls MA, Gan-Or Z* and Singleton A* (*equal contribution). Genetic modifiers of risk and age at onset in GBA associated Parkinson鈥檚 disease and Lewy body dementia. Brain. 2020. ;143(1):234-248. ,
Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, Tan M, Kia DA, Noyce AJ, Xue A, Bras J, Young E, von Coelln R, Sim贸n-S谩nchez J, Schulte C, Sharma M, Krohn L, Pihlstrom L, Siitonen A, Iwaki H, Leonard H, Faghri F, Gibbs JR, Hernandez DG, Scholz SW, Botia JA, Martinez M, Corvol JC, Lesage S, Jankovic J, Shulman LM, The 23andMe Research Team, System Genomics of Parkinson's Disease (SGPD) Consortium, Sutherland M, Tienari P, Majamaa K, Toft M, Brice A, Yang J, Gan-Or Z, Gasser T, Heutink P, Shulman JM, Wood N, Hinds DA, Hardy J, Morris HR, Gratten J, Visscher PM, Graham RR, Singleton AB, for the International Parkinson鈥檚 Disease Genomics Consortium. Parkinson鈥檚 disease genetics: identifying novel risk loci, providing causal insights and improving estimates of heritable risk. Lancet Neurology. 2019. 18(12);1091-1102. ,
Farazi Fard MA, Rebelo AP, Buglo B, Nemati H, Dastsooz H, Gehweiler I, Reich S, Reichbauer J, Quint谩ns B, Ord贸帽ez-Ugalde A, Cortese A, Courel S, Abreu L, Powell E, Danzi M, Martuscelli NB, Bis-Brewer DM, Tao F, Zarei F, Habibzadeh P, Yavarian M, Modarresi F, Silawi M, Tabatabaei Z, Yousefi M, Farpour HR, Kessler C, Mangold E, Kobeleva X, Mueller AJ, Haack TB, Tarnopolsky M, Gan-Or Z, Rouleau GA, Synofzik M, Sobrido MJ, Jordanova A, Sch眉le R, Zuchner S and Faghihi MA. Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia. American Journal of Human Genetics. 2019. 4;104(4):767-773.
Schormair B, Zhao C, Bell S, Tilch E, Salminen AV, P眉tz B, Dauvilliers Y, Stefani A, H枚gl B, Poewe W, Kemlink D, Sonka K, Bachmann CG, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA Wszolek Z, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Allen RP, Earley CJ, Ondo WG, Xiong L, Montplaisir J, Gan-Or Z, Perola M, Vodicka P, Dina C, Franke A, Tittmann L, Stewart AF, Shah SH, Gieger C, Peters A, Rouleau GA, Berger K, Oexle K, Di Angelantonio E, Hinds DA, M眉ller-Myhsok B and Winkelmann J. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurology. 2017;16 898-907.
Gan-Or Z, Bouslam N, Birouk N, Lissouba A, Chambers DB, V茅ri猫pe J, Androschuck A, Laurent SB, Rochefort D, Spiegelman D, Dionne-Laporte A, Szuto A, Liao M, Figlewicz DA, Bouhouche A, Benomar A, Yahyaoui M, Ouazzani R, Yoon G, Dupr茅 N, Suchowersky O, Bolduc F, Parker JA, Dion PA, Drapeau P, Rouleau GA, Ouled Amar Bencheikh B. Mutations in CAPN1 cause autosomal recessive Hereditary Spastic Paraplegia. American Journal of Human Genetics. 2016;98(5):1038-1046.
Gan-Or Z, Ozelius LJ, Bar-Shira A, Saunders-Pullman R, Mirelman A, Kornreich R, Gana-Weisz M, Raymond D, Rozenkrantz L, Deik A, Gurevich T, Gross SJ, Schreiber-Agus N, Giladi N, Bressman SB, and Orr-Urtreger A. The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease. Neurology 2013;80(17):1606-1610.
Gan-Or Z, Bar-Shira A, Dahary D, Mirelman A, Kedmi M, Gurevich T, Giladi N, Orr-Urtreger A. Sequence alterations in the putative promoter of RAB7L1 are associated with a reduced Parkinson disease risk. JAMA Neurology, 2012;69(1):105-10.
Sidransky E, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen C-M, Clark LN, Condroyer C, De Marco VE, D眉rr A, Eblan MJ, Fahn S, Farrer M, Fung H-C, Gan-Or Z, Gasser T, Gershoni R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen G-J, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nalls MA, Nicoletti G, Oliveira C, Orr-Urtreger A, Pereira L de Veiga, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Sammadar T, Schulte C, Manu Sharma M, Singleton A, Spitz M, Tan E-K, Tayebi N, Toda T, Troiano A, Tsuji S, Wolfsburg T, Wu Y-R, Zabetian CP, Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson disease. New England Journal of Medicine, 2009;361(17):1651-61.
Gan-Or Z, Giladi N, Rozovski U, Shifrin C, Rosner S, Gurevich T, Bar-Shira A, Orr-Urtreger A. Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology, 2008; 70: 2277鈥�83.
