Biosketch                Top

Ph.D. in Biochemistry and Molecular Biology (1992-1996) from the University of Calgary, Canada. Postdoctoral Fellow/Research Associate (1996-2001) in the Center for Research into Neurodegenerative Diseases at the University of Toronto, Canada. Dr. Yu joined the Center for Basic Neuroscience at UT Southwestern in October 2001.

 Research                 Top

Dr. Yu’s research interests focus on the molecular mechanisms of Alzheimer’s disease and related neurodegenerative disorders. Three research projects are currently underway:

1) The gamma-secretase complex and its mediated intramembrane proteolysis in neuronal plasticity and in Alzheimer's disease

2) Cell fate determination and stem cell biology

3) Molecular and cellular mechanism of neuroprotection.

 Recent Publications             Top   

Primary Research Articles

1. Premkumar S, Song Y, Sorbi S, Brindle N, Paterson A, Duara R, Levesque G, Yu G, Nishimura M, Ikeda M, O'Toole C, Kawarai T, Jorge R, Vilarino D, Bruni A, Farrer L, St George-Hyslop P (1998). Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA. 280, 614-618.
   
2. Brindle N, Song Y, Rogaeva E, Premkumar S, Levesque G, Yu G, Ikeda M, Nishimura M, Paterson A, Sorbi S, Duara R, Farrer L, St George-Hyslop P (1998). Analysis of the butyrylcholinesterase gene and nearby chromosome 3 markers in Alzheimer disease. Hum. Mol. Genet. 7, 933-935.
   
3. Song Y, Rogaeva E, Premkumar S, Brindle N, Kawarai T, Orlacchio A, Yu G, Levesque G, Nishimura M, Ikeda M, Pei Y, O'Toole C, Duara R, Barker W, Sorbi S, Freedman M, Farrer L, St George-Hyslop P (1998). Absence of association between Alzheimer disease and the -491 regulatory region polymorphism of APOE. Neurosci. Lett. 250, 189-192.
   
4. Yu G, Chen F, Levesque G, Nishimura M, Zhang D, Levesque L, Rogaeva E, Xu D, Liang Y, Duthie M, St George-Hyslop PH, Fraser PE (1998). The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J. Biol. Chem. 273, 16470-16475.
   
5. Tamaoka A, Fraser PE, Ishii K, Sahara N, Ozawa K, Ikeda M, Saunders A, Komatsuzaki Y, Sherrington R, Levesque G, Yu G, Rogaeva E, Shoji S, Nee L, Pollen D, Hendriks L, Martin J, Van Broeckhoven C, Roses A, Farrer L, St George-Hyslop P, Mori H (1998). Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease. Brain Res. Mol. Brain Res. 56, 178-185.
   
6. Nishimura M, *Yu G, Levesque G, Zhang D, Ruel L, Chen F, Milman P, Holmes E, Liang Y, Kawarai T, Jo E, Supala A, Rogaeva E, Xu D, Janus C, Levesque L, Bi Q, Duthie M, Rozmahel R, Mattila K, Lannfelt L, Westaway D, Mount H, Woodgett J, Fraser P, St George-Hyslop P (1999). Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of beta-catenin, a component of the presenilin protein complex. Nature Medicine 5, 164-169. (*co-first author)
   
7. Levesque G, *Yu G, Nishimura M, Zhang D, Levesque L, Yu H, Xu D, Liang Y, Rogaeva E, Ikeda M, Duthie M, Murgolo N, Wang L, VanderVere P, Bayne M, Strader C, Rommens J, Fraser P, St George-Hyslop P (1999). Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin. J. Neurochem. 72, 999-1008. (*co-first author)
   
8. Rogaeva E, Premkumar S, Grubber J, Serneels L, Scott WK, Kawarai T, Song Y, Hill D, Abou-Donia S, Martin E, Vance J, Yu G, Orlacchio A, Pei Y, Nishimura M, Supala A, Roberge B, Saunders A, Roses A, Schmechel D, Crane-Gatherum A, Sorbi S, Bruni A, Small G, Conneally P, Haines J, Leuven F, St. George-Hyslop P, Farrer L, Pericak-Vance M (1999). An alpha-2-macroglobulin insertion-deletion polymorphism in Alzheimer disease. Nature Genetics 22, 19-22.
   
9. Van Gassen G, De Jonghe C, Nishimura M, Yu G, Kuhn S, St George-Hyslop P, Van Broeckhoven C (2000). Evidence that the beta-catenin nuclear translocation assay allows for measuring presenilin 1 dysfunction. Mol. Med. 6, 570-580.
10. Smith S, Anderson HA, Yu G, Robertson A, Allen S, Tyler S, Naylor R, Mason G, Wilcock G, Roche P, Fraser P, Dawbarn D (2000). Identification of syntaxin 1A as a novel binding protein for presenilin-1. Brain Res. Mol. Brain Res. 78, 100-107.
    
11. Chen F, Yang D, Petanceska S, Yang A, Tandon A, Yu G, Rozmahel R, Ghiso J, Nishimura M, Zhang D, Kawarai T, Levesque G, Mills J, Levesque L, Song Y, Rogaeva E, Westaway D, Mount H, Gandy S, St George-Hyslop PH, Fraser PE (2000). Carboxyl-terminal fragments of Alzheimer beta-amyloid precursor protein accumulate in restricted and unpredicted intracellular compartments in presenilin 1-deficient cells. J. Biol. Chem. 275, 36794-36802.
    
12. Yu G, Chen F, Nishimura M, Steiner H, Tandon A, Kawarai T, Arawaka S, Supala A, Song Y, Rogaeva E, Holmes E, Zhang D, Milman P, Fraser P, Haass C, St George-Hyslop P (2000) Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes. J. Biol. Chem. 275, 27348-27353.
    
13. Zhang D, Levitan D, Yu G, Nishimura M, Chen F, Tandon A, Kawarai T, Arawaka S, Supala A, Song Y, Rogaeva E, Liang Y, Holmes E, Milman P, Sato C, Zhang L, St George-Hyslop P (2000). Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased A beta42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans. Neuroreport 11, 3227-3230.
    
14. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D, Holmes E, Milman P, Liang Y, Zhang D, Xu D, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (2000). Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and beta-APP processing. Nature 407, 48-54. (Note: comments in Nature 407, 34-35; Nature 408, 902-903; Science 289, 2296-2297).
    
15. Fergani A, Yu G, St George-Hyslop P, Checler F (2001). Wild-type and mutated nicastrins do no not display aminopeptidase M- and B-like activities. Biochem. Biophys. Res. Commun. 289, 678-680.
    
16. 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, Lee J, Song L, Zhang L, Fraser P, St George-Hyslop P (2001). Nicastrin binds to membrane-tethered Notch. Nature Cell Biology 3, 751-754. (*co-first author)
    
17. Levitan D, Yu G, St George Hyslop P, Goutte C (2001). APH-2/Nicastrin Functions in LIN-12/Notch Signaling in the Caenorhabditis elegans Somatic Gonad. Dev. Biol. 240, 654-661.
    
18. Rozmahel R, Huang J, Chen F, Liang Y, Nguyen V, Ikeda M, Levesque G, Yu G, Nishimura M, Mathews P, Schmidt S, Mercken M, Bergeron C, Westaway D, St George-Hyslop P (2002). Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP. Neurobiol Aging. 23, 187-194.
    
19. Yang D, Tandon A, Chen F, Yu G, Yu H, Arawaka S, Hasegawa H, Duthie M, Schmidt S, Nixon R, Ramabhadran T, Mathews P, Gandy S, Mount H, St George-Hyslop P, Fraser P (2002). Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins. J. Biol. Chem. 277, 28135-28142.
    
20. Arawaka S, Hasegawa H, Tandon A, Janus C, Chen F, Yu G, Kikuchi K, Koyama S, Kato T, Fraser P, St George-Hyslop P (2002). The levels of mature glycosylated nicastrin are regulated and correlate with gamma-secretase processing of amyloid beta-precursor protein. J. Neurochem. 83, 1065-1071.
    
21. Rozmahel R, Mount HT, Chen F, Nguyen V, Huang J, Erdebil S, Liauw J, Yu G, Hasegawa H, Gu Y, Song YQ, Schmidt SD, Nixon RA, Mathews PM, Bergeron C, Fraser P, Westaway D, St. George-Hyslop P (2002). Alleles at the Nicastrin locus modify presenilin 1-deficiency phenotype. Proc Natl Acad Sci U S A. 99, 14452-144527.
    
22. Lee S, Shah S, Li H, Yu C, Han W, Yu G (2002). Mammalian APH-1 Interacts with Presenilin and Nicastrin and Is Required for Intramembrane Proteolysis of Amyloid-beta Precursor Protein and Notch. J. Biol. Chem. 277, 45013-45019.
    
23. Luo W, Wang H, Li H, Kim B, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H (2003). PEN-2 and APH-1 Coordinately Regulate Proteolytic Processing of Presenilin 1. J. Biol. Chem. 278, 7850-7854.
    
24. Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, and Yu G (2004). A Conserved GXXXG Motif in APH-1 Is Critical for Assembly and Activity of the Gamma-Secretase Complex. J. Biol. Chem. 279, 4144-4152.
    
25. Hansson EM, Stromberg K, Bergstedt S, Yu G, Naslund J, Lundkvist J, Lendahl U (2005). Aph-1 interacts at the cell surface with proteins in the active gamma-secretase complex and membrane-tethered Notch. J. Neurochem. 92, 1010-1020.
    
26. Shah S, Lee S, Tabuchi K, Hao Y, Yu C, LaPlant Q, Ball H, Dann C, S|dhof T, and Yu G (2005). Nicastrin Functions As A Gamma-Secretase-Substrate Receptor. Cell 122, 435-447 (Note: comment in Cell 122, 318-320).

INVITED REVIEWS

1. Fraser P, Yu G, Levesque G, Ikeda M, Nishimura M, Rogaeva E, Westaway D, St George-Hyslop P, Carlson G. Molecular Genetics of the Presenilins in Alzheimer’s Disease. In Presenilins and Alzheimer’s Disease (Eds. S.G. Younkin, R. Tanzi and Y. Christen), Springer-Verlag, Berlin, pp.1-10, 1998.
   
2. Fraser P, Levesque G, Yu G, Mills L, Thirlwell J, Frantseva M, Gandy S, Seeger M, Carlen P, St George-Hyslop P (1998). Presenilin 1 is actively degraded by the 26S proteasome. Neurobiol. Aging 19:S19-21.
   
3. Nishimura M, Yu G, St George-Hyslop P (1999). Biology of presenilins as causative molecules for Alzheimer disease. Clin. Genet. 55, 219-225.
   
4. Fraser P, Yang D, Yu G, Levesque L, Nishimura M, Arawaka S, Serpell LC, Rogaeva E, St George-Hyslop P (2000). Presenilin structure, function and role in Alzheimer disease. Biochim. Biophys. Acta 1502, 1-15.
   
5. Yu G, Chen F, Nishimura M, Steiner H, Tandon A, Kawarai T, Arawaka S, Supala A, Song Y, Rogaeva E, Holmes E, Zhang DM, Milman P, Fraser P, Haass C, St George-Hyslop P (2000). Mutation of conserved aspartates affects maturation of presenilin 1 and presenilin 2 complexes. Acta Neurol. Scand. Suppl. 176:6-11.
   
6. Fraser P, Yu G, Levesque L, Nishimura M, Yang DS, Mount H, Westaway D, St George-Hyslop P (2001). Presenilin function: connections to Alzheimer's disease and signal transduction. Biochem. Soc. Symp. 67, 89-100. [Also in Neuronal Signal Transduction and Alzheimer's Disease (Ed. C. O'Neill and B. Anderton), Portland Press, London, 2001]
   
7. Chen F, Yu G, Arawaka S, Nishimura M, Kawarai T, Yu H, Tandon A, Supala A, Song YQ, Rogaeva E, Milman P, Sato C, Janus C, Lee J, Song L, Zhang L, Fraser P, St George-Hyslop P. Further analysis of the Nicastrin:Presenilin Complex. In Notch from Neurodevelopment to Neurodegeneration: Keeping the Fate (Eds. Israel, De Strooper, Checler, and Christen). Springer-Verlag, Berlin, pp.109-117, 2002.

 Current Lab Staff                 Top

Dr. Yu’s laboratory currently has positions open for graduate students and postdoctoral fellows. Interested candidates with strong background in biochemistry, mouse genetics, cell biology, molecular and cellular biology, and/or other areas of biomedical research are encouraged to apply.

Rooms NA4.508
Telephone: 214-648-4119

Postdoctoral Fellows

Students