Luo, Wenjie

Wenjie Luo, Ph.D.
Associate Professor of Neuroscience

 https://appel.weill.cornell.edu/profiles/dr-wenjie-luo

Overview 

My research investigates the mechanism of brain pathologies and deregulated cellular cascades that have important implications for understanding Alzheimer’s disease (AD) progression. I am currently exploring the mechanism of Apolipoprotein E (the most influential genetic risk factor for the late-onset familial Alzheimer’s disease) mediated amyloid metabolism in search for therapeutic tools against AD. In addition, I am investigating the role of Hsp90 in AD; specifically the molecular mechanisms of how Hsp90 regulates tau aggregation, amyloid deposition and aberrant cellular events in AD-related cell models and animal models. In addition, my research focuses on brain amyloid, which is generated by sequential cleavages from its precursor protein APP in specific intracellular compartments. Deregulated intracellular trafficking of APP is one of the important risk factors for brain amyloid accumulation. I study protein factors regulating the intracellular trafficking of APP and its cleavage enzymes, beta-secretase and gamma-secretase while addressing some fundamental aspects of how the intracellular trafficking influences amyloid accumulation in AD brain. I am to understand the molecular basis of pathogenic processes in Alzheimer’s disease

Achievements & Publications

Pioneer in identifying the role of Hsp90 in regulating tau aggregation; Pioneer in revealing and exploring the therapeutic role of PU-class Hsp90 inhibitor using neurodegenerative mouse models.

1. Luo W, Wang H, Li H, Kim BS, 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(10):7850 7854. PMID: 12522139
2. Wang H., Luo W, Li YM., Thinakaran G., Greengard P., and Xu H. (2004) Presenilin 1 and γ-secretase inhibitors affect intracellular trafficking and cell surface accumulation of the g-secretase complex components. J Biol Chem. 279(39):40560-6. PMID: 15247291
3. Zhang YW, Luo, W., Wang H., Lin, P., Vetrivel, P.S., Li, F., Wong, P.C., Farquhar, M.G., Thinakaran, G., Xu, H., (2005) Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem., 280(17):17020-6. PMID: 19914182
4. Luo W, Dou F., Rodina A., Chip S., Kim J., Zhao Q., Moulick K., Aguirre J., Wu N., Greengard P., and  Chiosis G., (2007) Roles of Hsp90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies, Proc Natl Acad Sci U S A., 104(22):9511-6. PMID: 17517623
5. Luo W,  Rodina A., Chiosis G. (2008) Heat shock protein 90: translation from cancer to Alzheimer’s disease treatment? BMC Neuroscience, 9 Suppl 2:S7. PMID: 19090995
6. Zhang YW, Liu S., Zhang X., Li Wb., Chen Y., Huang X., Sun L., Luo, W., Netzer WJ., Threadgill R., Wiegand G., Wang R., Cohen SN., Greengard P., Liao F., Li L., Xu H., (2009) A functional mouse retroposed gene fg01 inhibits Alzheimer's β-amyloid generation and tau phosphorylation. Neuron., 64(3):328-340. PMID: 19914182
7. Ahn J.H., Luo W., Kim J., Rodina A., Clement CC., Aguirra J., Sun W., Kang Y., Maharaj R., Moulick K., Zatorska D.,  Brodsky J., Chiosis G. (2010) Assay platform for discovery and evaluation of pharmacologic heat shock protein modulators. ASSAY and Drug Development Technologies, Dec 6. [Epub ahead of print] PMID: 21133677.
8. He G, Luo W, Li P, Remmers C, Netzer W, Flajolet M, Gorelick F, Wennogle LP, Greengard P.(2010) Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature. Sep 2;467(7311):95-8. PMID: 20811458
9. Luo, W, Sun W, Toldone T, Rodina A, Chiosis G (2010) Heat shock protein 90 in neurodegenerative diseases. Molecular Neurodegeneration 5:24. 
10. Bettayeb K, Oumata N, Zhang Y, Luo W, Bustos V, Galons H, Greengard P, Meijer L, Flajolet M. (2012) Small-molecule inducers of Aβ-42 peptide production share a common mechanism of action. FASEB J. 26(12):5115-23. PMID:22972917.