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Prof. St George-Hyslop’s research focuses on the molecular mechanisms that cause neurodegeneration in Alzheimer’s disease and the mechanisms by which the presenilin protein complex generates a neurotoxic peptide that plays a central role in this disease. His important discoveries have led to the design of potential therapies and in understanding the mechanism of neurodegeneration in other neurodegenerative diseases. View Peter St George-Hyslop’s Wellcome Trust video on Alzheimer’s Disease research here.
Peter St George-Hyslop is the acclaimed director of the Tanz Centre for Research in Neurodegenerative Disease and a professor in the University of Toronto’s Division of Neurology. He received his M.D. from the University of Ottawa, specialized in internal medicine and neurology and conducted postdoctoral research at the University of Toronto and at Harvard Medical School.
Prof. St George-Hyslop was an instructor in neurology and genetics at Harvard University and assistant physician in the Departments of Neurology and Genetics at Massachusetts General Hospital before assuming his current position at the University of Toronto in 1991, where now he holds the rank of University Professor, the University’s highest academic post.
Höglinger GU, Melhem NN, Dickson D, Sleiman PMA, Wang LS, Klei L, Rademakers R, de Silva R, ILitvan, Riley DC, van Swieten JC, Heutink P, Wszolek Z, Uitti RJ, Vandrovcova R, Hurtig H, Gross RG, Maetzler G, Goldwurm G, Tolosa1 E, Borroni B, Pastor P, PSP Genetics Study Group† Rogaeva, E, Hazrati L, St George Hyslop P, Cantwell LB, Devlin B, Hakonarson H, Müller G, Schellenberg GD. Common variants affect risk for the tauopathy Progressive Supranuclear Palsy, Nature Genetics 43: 699-705, 2011.
Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider D, Carrasquillo MM, Ertekin-Taner NL, Younkin SG, Cruchaga S, Kauwe JFK, Nowotny P, Kramer P, Hardy J, Huentelman MJ, Myers AJ, Barmada K, Demirci FY, Baldwin CT, Green RG, Rogaeva E, St George-Hyslop P, Alzheimer Disease Genetics Consortium#, Cantwell LB, Dombroski BA, Beekly DE, Haines JL, Mayeux RP, Pericak-Vance MA, Farrer LA, Schellenberg GD. Common variants in MS4A4/MS4A6E, CD2AP, CD33, and EPHA1 are associated with late-onset Alzheimer's disease. Nature Genetics 43: 436-441, 2011
St George-Hyslop P, Schmitt-Ulms G. Alzheimer's disease: Selectively tuning gamma-secretase. Nature, 467:36-37, (2010).
St George-Hyslop P, Haass C. Regulatory RNA goes awry in Alzheimer's disease. Nature Medicine. 2008 14:711-712 (2008).
Rogaeva E, Meng Y, Lee JH, Gu YJ, Kawarai K, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland RP, Inzelberg R, Hampe W, Bujo H, Song Y, Andersen OM, Willnow TE, Graff-Radford N, Petersen RC, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux RP, Farrer LA, St George-Hyslop The neuronal sortilin-related receptor SORL is genetically associated with Alzheimer's Disease. (2007) Nature Genetics, 39:168-177.
Chen F, Hasegawa H, Schmitt-Ulms G,Kawarai T, Bohm C, Katayama T, Gu YJ, Sanjo N, Glista M, Rogaeva E, Wakutani Y, Pardossi Piquard R, Ruan Y, Tandon A, Checler F, Marambaud P, Hansen K, Westaway D, St George-Hyslop P, Fraser PE. TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. (2006) Nature. 440:1208-1212.
McLaurin J, Kierstead, ME, Brown ME, Hawkes CA, Lambermon MHL, Phinney AL, Darabie AL, Cousins JE, French E, Lan MF, Chen F, Wong SNS, Mount HTJ, Fraser PE, Westaway, DA and St George-Hyslop, P. Cyclohexanehexol inhibitors of Aβ-aggregation prevent and reverse Alzheimer phenotype in a mouse model. (2006) Nature Medicine 12:801-808.
Pardossi-Piquard R, Petit A, Kawarai T, Sunyach C, Alves da Costa C, Vincent B, Ring S, D'Adamio L, Shen J, Muller U, St George Hyslop P, Checler F. Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. (2005) Neuron. 46:541-554.
Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Van Oene M, Newman B, Cescon D, Cohen Z, Griffiths AM, Greenberg GR, McLeod RS, Steinhart H, St George-Hyslop PH, Siminovitch KA. (2004) Mutations of the OCTN1 and OCTN2 cation transporter genes are associated with Crohn's disease. Nature Genetics, 6:471-475.
Sisodia S, St George-Hyslop PH. (2002) "γ-secretase, Notch, Aβ and Alzheimer's Disease: Where do the presenilins fit in?" Nature Reviews Neuroscience 3: 281-290.
McLaurin J, Cecal R, Kierstead ME, Tian X, Phinney AL, Manea M, French JE, Lambermon MHL, Darabie AA, Brown ME, Chishti MA, Horne P, Westaway D, Fraser PE, Mount HTJ, Przybylski M, St George-Hyslop PH. (2002) Therapeutically effective anti-Aβ antibodies target Aβ residues 4-10 and inhibit cytotoxicity and fibrillogenesis. Nature Medicine 8: 1263-1269.
Chen F, Yu G, Arawaka S, Nishimura M, Kawarai T, Yu H, Tandon A, Supala A, Song Y, Rogaeva E, Milman P, Sato C, Yu C, Janus C, Song L, Zhang L, Fraser PE, St George-Hyslop PH. (2001) Nicastrin binds to membrane-tethered Notch. Nature Cell Biol. 3:751-54.
Janus C, Pearson J, McLaurin J, Mathews P, Jiang Y, Schmidt S, Chishti MA, Horne P, Heslin D, French J, Mount H, Nixon R, Mercken M, Bergeron C, Fraser P, St George-Hyslop P, Westaway D. (2000) Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature. 408 (21/28 Dec.): 979-982.
Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y-Q, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D-S, Holmes E, Milman P, Liang Y, Zhang D-M, Xu D-H, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer L, Sorbi S, Bruni AC, Fraser PE, St George-Hyslop PH. (2000) Nicastrin modulates presenilin-mediated Notch/Glp1 signal transduction and βAPP processing. Nature 407: 48-54.
Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, Hitomi J, Morihara T, Yoneda T, Gomi F, Mori Y, Nakano Y, Takeda J, Tsuda T, Itoyama Y, Murayama O, Takashima A, St George-Hyslop P, Takeda M, Tohyama M. (1999) Presenilin 1 mutation down regulates the signalling pathway of unfolded protein response and increases vulnerability to ER stress. Nature Cell Biol. 1: 479-485.
Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, Mar L, Sorbi S, Nacmias B, Piacentini S, Amaducci L, Chumakov I, Cohen D, Lannfelt L, Fraser PE, Rommens JM, St George-Hyslop PH. (*1995) Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's Disease type 3 gene. Nature 376: 775-778.
Sherrington R, Rogaev E, Liang Y, Rogaeva E, Levesque G, Ikeda MH, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin J-F, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee Y, Chumakov D, Pollen D, Tanzi RE, Wasco W, Haines JL, Da Silva R, Pericak-Vance MA, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH. (1995) Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer Disease. Nature 375: 754-760.
Saunders AM, Strittmatter WJ, Schmechel S, St George-Hyslop P, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-McLachlan DR, Growdon J, Alberts MJ, Hulette C, Crain B, Goldgaber D, Roses AD. (1993) Association of Apolipoprotein E allele e4 with late-onset familial and sporadic Alzheimer Disease. Neurology 43: 1467-1472.
St George-Hyslop PH, Haines JL, Rogaev EI, Mortilla M, Vaula G, Pericak-Vance MP, Foncin J-F, Montesi M, Bruni A, Sorbi S, Rainero I, Pinessi L, Pollen D, Polinsky R, Nee L, Kennedy J, Macciardi F, Rogaeva E, Liang Y, Alexandrova N, Lukiw W, Schlumpf K, Tanzi R, Tsuda T, Farrer L, Cantu J-M, Duara R, Amaducci L, Bergamini L, Gusella J, Roses A, Crapper McLachlan D. (1992) Genetic Evidence for a novel Familial Alzheimer's Disease gene on chromosome 14. Nature Genetics 2, 330-334.
St George Hyslop PH, Haines JL, Farrer LA, Polinsky R, van Broeckhoven C, Goate A, McLachlan DR, Orr H, Montesi MP, Sorbi S, Rainero I, Foncin J-F, Pollen D, Cantu J-M, Vartanjan M, Mayeux R, Nee L, Backhovens H, Martin J-J, Rossor M, Owen MJ, Mullan M, Percy ME, Karlinsky H, Rich S, Growdon J, Heston L, Gusella JF, Hardy J. (1990) Genetic linkage studies suggest that Alzheimer's Disease is not a single homogeneous disorder. Nature 347: 194-197.
His honours include the Francis A. McNaughton Prize from the Canadian Neurological Society and the Award for Medical Research from the Metropolitan Life Foundation. He was a Medical Research Council of Canada (now the Canadian Institutes of Health Research) Scholar in 1991 and a Distinguished Scientist in 2000. He received the Gold Medal in Medicine from the Royal College of Physicians of Canada in 1994 and the Michael Smith Award from the Canadian Institutes of Health Research in 1997. In 1995, he became a member of the American Society for Clinical Investigation, and he is a fellow of the Royal Society of Canada. In 2004 he was awarded the Oon International Award in Preventive Medicine from the University of Cambridge, and in 2007 he was elected as a foreign member to the Institute of Medicine of the National Academy of Sciences. Dr. St George Hyslop is also a Howard Hughes International Scholar, Fellow of the Royal Society of London.