教授 博士生导师 教育部长江学者讲座教授 1983年毕业于南京大学生物系人体及动物生理学专业获理学学士学位 1986年毕业于中国科学院上海生理研究所生理学专业获生理学硕士学位 1989年毕业于美国纽约州立大学心理生物学及神经科学专业获得心理学博士 曾先后在荷兰皇家科学院Rudolf Magnus药物研究所(Rudolf Magnus奖金)学习并在美国国立卫生研究院 (NIH) 精神卫生(NIMH) 和神经病学及中风研究所(NINDS) 从事博士后及助理研究员研究。
1993年因克隆并药理学鉴定出新的多巴胺第5受体,五羟色胺第6第7受体特邀加入美国亚培实验室(Abbott Labs)神经科学部神经免疫探索研究小组 (Neuroimmunology Exploratory Group),任组长及资深分子神经药理学家, 参与制定和发展治疗神经退行性病(Alzheimer’s and Parkinson’s diseases) 药物。1997年任职于亚利桑那州太阳医学健康研究所(Sun Health Research Institute) L.J.罗伯特阿尔茨海默病研究中心(L. J. Roberts Center for Alzheimer’s Disease)主任和资深科学家(终身教授)并兼任亚利桑那州立大学分子细胞生物学教授,2000年起转任哈德曼分子及细胞神经生物学实验室主任,资深科学家及分子生物学教授工作多年。 2006年申勇教授兼任美国SunHealth亚太医学研究中心共同主任。2010年申勇教授加盟于佛罗里达州的罗斯坎普医学研究所(Roskamp Institute)担任脑疾病及治疗战略研究及治疗中心主任,资深科学家及佛罗丽达大学医学院神经病学教授继续从事神经疾病的研究。主要研究方向是阿尓茲海默、帕金森等神经退行性病及相关脑血管病的基础及转化研究,包括寻找并分子克隆脑疾病的新基因,对新蛋白的鉴定,发展新型细胞及动物模型对脑疾病病理及细胞分子机制的研究以及新药的开发。并牵头美国,欧盟多中心寻找并确定临床早期诊断老年神经退行病标记物和参与相关药物临床实验。共发表100余篇有关神经发育疾病,神经递质新受体的分子克隆和药理学鉴定,神经退变性疾病的分子机制及病理,神经免疫等方面的文章(Nature Medicine, Journal of Cell Biology, Cell Molecular Cell, JAMA Psychiatry, Neuron, Proc. Natl. Acad. Sci. USA, Brain, Neurology, Journal of Neuroscience, 等重要生物医学国际学术期刊。获得多项奖项及荣誉称号包括:阿尔茲海默病领域里的“先锋奖(Zenith Award)”以及“阿尔兹海默病研究杰出贡献奖(Outstanding Contributor to Alzheimer Research)”, 以及2009年教育部颁发的“长江学者奖励计划特聘讲座教授”。2014年回国任中国科学技术大学教授。
研究兴趣及方向:
1) 脑功能及疾病(神经退行性疾病和精神疾病)的分子机制研究包括脑内基因特别表达和调控和新基因的发现
2) 神经退行性疾病和精神疾病新治疗靶点的分子病理学鉴定以及药物发现
3) 新型脑疾病的早期临床诊断性标记物的发现和研究
主要代表论文:
1. Yang LB, Lindholm K, Yan R, Citron M, Xia W, Beach T, Sue L, Wong P, Price D, Li R, Shen Y. (2003). Elevated β-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nature Medicine, 9(1): 3-4.
2. Li R, Yang LB, Lindholm K, Yan R, Citron M, Beach T, Sue L, Subbagh M, Cai H, Wong P, Price D, Shen Y. (2004). Aβ load is correlated with elevated BACE activity in sporadic Alzheimer patients. Proc Natl Acad Sci USA, 101(10), 3632-3637.
3. Li R., Lindholm K, Yang LB, Konishi Y, Hampel H, Zhang, D. Shen Y. (2004). TNF death receptor signaling cascade is required for amyloid-protein induced neuron death. Journal of Neuroscience, 28(7):1760-1771.
4. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, Harada N, Zhong Z, Shen Y, Li R. (2005). Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci USA, 102(52):19198-203.
5. Zhong, Z., Ewers, M., Teipel, S., Büger, K., Wallin, A., Blennow, K., Hampel, H., and Shen Y.(2007). High Levels of β-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment, the early stage of Alzheimer’s Disease, JAMA Psychiatry(Archives of General Psychiatry), 64(6):718-2.
6. HeP, ZhongZ, LindholmK, BerningL, LeeW, LemereC, StaufenbielM, LiR and Shen Y. (2007). Deletion of TNF death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer’s mice. Journal of Cell Biology, 178(5): 829-841.(Highlighted by Nature Oct. 2007: Death receptor takes centrestage ; Hot story news by Science, 2007 : Death receptor and Alzheimer.
7. Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, Hiltunen M, Yang SH, Zhong Z, Shen Y, Simpkins JW, Tanzi RE. (2007). Depletion of GGA3 stabilizes BACE and enhances β-secretase activity. Neuron. 54(5): 721-37.
8. Ewers M, Zhong Z, Bürger K, Wallin A, Blennow K, Teipel SJ, Shen Y, Hampel H. (2008). Increased CSF-BACE1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment (MCI) and Alzheimer's disease. Brain, 131(Pt 5): 1252-8.
9. He, P. and Shen Y. (2008).Interruption of β-catenin signaling reduces neurogenesis in Alzheimer’s disease’s brains.Journal of Neuroscience. (2009), 29(20): 6545-57.
10. Xia W., Yang T., Imelda M. Smith I. M., Shen Y., Walsh D. M. and Selkoe, D. J. (2009). A specific ELISA for measuring amyloid β-protein oligomers in human plasma and the brains of Alzheimer patients. JAMA Neurology(Archives of Neurology), 66(2): 190-9.
11. Min S-W, Cho S-H, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Huang EJ, Shen Y, Masliah E, Mukherjee C, Meyers D, Cole PA, Ott M, Li Gan L (2010). Acetylation of tau inhibits Its degradation and contributes to tauopathy. Neuron, 67: 953-966.
12. HeP, LiuQ, WuJ and Shen Y (2011). Genetic Deletion of TNF Receptor Suppresses Excitatory Synaptic Transmission via Reducing AMPA Receptor Synaptic Localization in Cortical Neurons. FASEB Journal. 26(1): 334-45.
13. Walker KR, Kang EL, Whalen MJ, Shen Y and Tesco G. (2012). Depletion of GGA1 and GGA3 mediates post-injury elevation of BACE1. Journal of Neuroscience. 32(30): 10423-37.
14. JiangH, HeP, AdlerCH,ShillH,BeachTG, Li, R, and ShenY. (2012). Bid Signal Pathway Components are identified in the Temporal Cortex in Brains with Parkinson’s disease dementia. Neurology, 79(17): 1767-73.
15. Wang H, Li R and Shen Y (2013). β-secretase: Its Biology as a Therapeutic Target in Diseases.Trends in Pharmacological Sciences. 34(4):215-25.
16. HeP, ChengX, StaufenbielM, LiR and Shen Y (2013). Long-term treatment of TNF inhibitor, thalidomide, ameliorates Alzheimer-like pathology through inhibition of β-secretasein a mouse model of Alzheimer’s disease. PLoS One, 8(2): e55091.
17. Cho HJ, Jin SM, Ding J, Xie C, Yu J, Parisiadou L, Sun L, Vancraenenbroeck R, Lobbestael E, Baekelandt V, Taymans J-M, He P, Troncoso J, Shen Y, Cai H (2013). MicroRNA-205 regulates the Expression of Parkinson’s disease-related Leucine-rich Repeat Kinase 2 Protein. Human Molecular Genetics, 22(3):608-20.
18. Cheng X, He P, Yao H, Dong Q, Li R, Shen Y (2014). Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy. Neurology. 82(19): 1707-1715.
19. Jiang H, He P, Xie J, Staufenbiel M, Li R, Shen Y. (2014). Genetic deletion of TNFRII gene enhances the Alzheimer-like pathology in an APP transgenic mouse model via reduction of phosphorylated IκBα. Human Molecular Genetics. 23(18):4906-4918.
20. KonishiY, YangLB, HeP, LindholmK, LuB, Li Rand Shen Y. (2014). Deficiency of GDNF receptor GFRα1 in Alzheimer Neurons Results In Neuronal Death. Journal of Neuroscience, Sept. 24, 34(39):13127-13138.
21. Cheng X, Shen Y and Li R (2014). Targeting TNF: A therapeutic strategy for Alzheimer’s disease. Drug Discovery Today, Jul 3. pii: S1359-6446(14)00271-2.
联系方式:yongshen@ustc.edu.cn
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