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许华曦 教授

点击次数:更新时间:2021年11月17日

重庆医科大学杰出教授、博士生导师、300深夜看黄禁用免费院长                                                           

美国科学促进会会士(AAAS Fellow)

海外高层次人才、国家(海外)杰出青年科学基金获得者

厦门大学神经科学研究所荣誉所长


     办公电话:023-68480608

     邮    箱:Huaxi.Xu@MolecularNeurodegeneration.org


研究方向:

阿尔茨海默病等脑疾病相关的神经分子及细胞生物学、神经信号转导、神经突触毒性、神经免疫功能等。


个人简介:

许华曦教授是国际顶级神经科学期刊Molecular Neurodegeneration杂志(SCI影响因子18.907)创办人/(共同)主编,1993年获爱因斯坦医学院博士学位、1994-1998年在诺贝尔奖得主Greengard教授指导下从事博士后研究,1998-2003年任洛克菲勒大学助理教授,2003-2019年任Sanford Burnham Prebys医学研究所教授、神经科学部/计划主任、Jeanne & Gary Herberger讲席教授。

许华曦教授是国际阿尔兹海默病研究的权威专家之一,在国际学术杂志(SCI)发表论文190多篇,被引用25600余次,H指数79,入选2021爱思唯尔“中国高被引学者”。担任独立PI二十三年多,主持过数千万美元的科研经费项目;近两年来获得国家自然科学基金委重大研究计划集成项目、重点项目的支持,科技创新2030-"脑科学与类脑研究"重大项目(脑衰老机制及调控研究)首席科学家。其实验室先后培养了一百多名博士研究生、博士后或其他研究人员,其中多人已在国际知名大学/研究机构担任正教授、副/助理教授或各医药、生物技术公司任职,培养了多名国家杰青、优青等国家级人才。荣获包括美国老年痴呆症协会的首届Courage and Hope奖和Zenith Fellow (协会顶尖会员)奖、Ellison医学基金会杰出青年学者奖、Ruth Salta青年成就奖、中国侨联第九届“侨界贡献奖”等奖项。受邀担任国际学术会议大会主席或在国际知名研究机构做学术报告(约200次)。先后为世界多个基金委员会评审科研基金,多次担任国家自然科学基金委面上项目、重点项目以及各类国家级人才项目函/会评专家,为多个国际顶级期刊审稿和撰写综述。


代表性成果:

1. Zheng Q, Song B, Li G, Cai F, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang XF, Luo H, Zhang X, Zhang H, Zeng Z, Huang TY, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H*, Song W*, Wang X*.  (2022) USP25 inhibition ameliorates Alzheimer's pathology through the regulation of APP processing and Aβ generation. J Clin Invest. 2022 Mar 1;132(5):e152170. doi: 10.1172/JCI152170. PMID: 35229730. (*Co-corresponding authors)

2. Zhang Q, Zhang J, Ye J, Li X, Liu H, Ma X, Wang C, He K, Zhang W, Yuan J, Zhao Y, Xu H*, Liu Q*. (2021) Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing. Mol. Neurodegener. 16(1):66. doi: 10.1186/s13024-021-00485-w. PMID: 34551807. (*Co-corresponding authors)

3. Xu P, Chang JC, Zhou X, Wang W, Bamkole M, Wong E, Bettayeb K, Jiang LL, Huang T, Luo W, Xu H, Nairn AC, Flajolet M, Ip NY, Li YM, Greengard P. (2021) GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease.J. Exp. Med. 218(8):e20202446. doi: 10.1084/jem.20202446. PMID: 34156424

4. Zheng, Q., Li, Q., Wang, S., Zhou, Y., Liu, K., Yue Gao; Zhou, Y., Zheng, L., Zhu, L. Deng, Q. Wu, M., Di, A., Zhang, L, Zhao, Y., Zhang, H., Sun, H. Dong, C., Xu, H., and Wang, X. (2020) Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25. Science Advances. 7(1):eabe1340. doi: 10.1126/sciadv.abe1340. PMID: 33523861.

5. Liu, T., Zhu, B., Liu, Y., Zhang, X., Yin, J.  Li, X., Jiang, L-L., Hodges, A., Rosenthal, S.B., Zhou, L., Yancey, J., Ms. McQuade, A., Blurton-Jones, M., Tanzi, R.E., Huang, T.Y. and Xu, H. (2020) Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE. J. Exp. Med. 7;217(12):e20200474. doi: 10.1084/jem.20200474.

6. Guo, T.T., Zhang, D., Zeng, Z., Huang, T., Xu, H.* and Zhao, Y*. (2020) Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol. Neurodegener. 15(1):40. doi: 10.1186/s13024-020-00391-7.*co-correspondent authors

7. Jiang, L-L., Zhu, B., Zhao, Y., Li, X., Liu, T., Piña-Crespo, J.C., Zhou, L., Xu, W., Rodriguez, M.J., Yu, H.Y., Cleveland, D.W., Ravits, J.M., Da Cruz, S., Long, T., Huang, T.Y, and Xu, H. (2019) Membralin deficiency dysregulates astrocytic glutamate homeostasis leading to ALS-like impairment. J. Clin. Invest. 130:3103-3120.

8. Huang, T.Y. and Xu, H. (2019) Bringing Order Out of Chaos: Establishing an Epistatic Relationship Between CD33 and TREM2. Neuron. 103:747-749.

9. Du, Y., Zhao, Y., Li, C., Zheng, Q., Tian, J., Li, Z., Huang, T.Y., Zhang, W., and Xu, H. (2018) Inhibition of PKCδ reduces amyloid-beta levels and reverses Alzheimer Disease phenotypes. J. Exp. Med. 215(6):1665-1677.

10. Zhao, Y., Wu, X., Li, X., Jiang, L-L., Gui, X., Liu, Y., Sun, Y., Zhu, B., Pina-Crespo, C.C., Zhang, N., Chen, X., Bu, G., An, Z., Huang, T.Y., and Xu, H. (2018) TREM2 is a receptor for β-amyloid medicating microglial function. Neuron 97(5):1023-1031.

11. Zhu, B., Jiang L-L., Huang, T., Zhao, Y., Liu, T., Zhong, Y., Campos A., Pomeroy, K., Masliah, E., Zhang, D., and Xu, H. (2017) ER-associated degradation regulates γ-secretase activity, memory function and Alzheimer’s amyloid pathology. Nature Communications, 8(1):1472.

12. Huang, T., Zhao, Y., Jiang, L-L., Li, X., Liu, Y., Sun, Y., Pina-Crespo, J., Zhu, B., Masliah, E., Willnow, T.E., Pasquale, E.B., and Xu, H. (2017) SORLA attenuates EphA4 signaling and beta-amyloid-induced neurodegeneration. J. Exp. Med. 36:7996-8011.

13. Zhao, Y., Tseng, IC., Heyser, CJ. Rockenstein, E., Mante M., Adame, A., Zheng, Q., Huang, T., Wang, X., Arslan, PE., Chakrabarty P., Wu, C., Bu, G., Mobley, WC., Zhang, YW., St. George-Hyslop, P., Masliah, E., Fraser, P., and Xu, H. (2015) Appoptosin-mediated caspase-cleavage of tau contributes to progressive supranuclear palsy pathogenesis. Neuron 87(5):963-75.

14. Tu, S., Okamoto SI., Lipton, SA., and Xu, H. (2014) Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease. Mol. Neurodegener. 9(1):48. PMCID: PMC4237769.

15. Wang, X., Zhao, Y., Zhang, X., Badie, H., Zhou, Y, Mu, Y, Loo, LS., Cai, L., Thompson, R., Yang, B., Chen, Y., Johnson, PF., Wu, C., Mobley, W., Zhang, D., Gage, FH., Ranscht, B., Zhang, YW., Lipton, SA., Hong, W., and Xu, H. (2013) Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulation of glutamate receptor recycling in Down’s Syndrome. Nature Medicine 19(4):473-80.

16. Liu, CC., Kanekiyo, T., Xu, H., and Bu, G. (2013) Apolipoprotein E and Alzheimer’s disease: risk, mechanisms, and therapy. Nature Review Neurology 9(2):106-18. PMCID: PMC3726719

17. Zhang, YW., and Xu, H. (2010) Substrate check for gamma-secretase. Nat. Struct. & Mol. Biol.17(2):140-1.

18. Zhang, YW., Liu, L., 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, FF., Li, L., and Xu, H. (2009) A functional mouse retroposed gene Rps23r1 reduces Alzheimer’s beta-amyloid levels and tau phosphorylation. Neuron 64(3):328-40.

19. Zhang, YW, Wang, R., Liu, Q., Zhang, H., Liao, FF., and Xu, H. (2007) Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proc. Natl. Acad. Sci. 104(25):10613-8.

20. Cai, D., Zhong, M., Wang, R., Netner, WJ., Shields, D., Zheng, H., Sisodia SS., Foster, DA., Gorlick, SF., Xu, H.*, and Greengard, P*. (2006) Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons. Proc. Natl. Acad. Sci. 103(6):1936-40. (*, Co-correspondent Authors).

21. Gasparini, L and Xu, H. (2003) Potential roles of insulin and IGF-1 in Alzheimer's disease. Trends in Neurosciences 26(8):404-6.

22. Dou, F., Netzer, WJ., Tanemura, K., Li, F., Hartl, FU., Takashima, A., Gouras GK., Greengard, P., and Xu, H. (2003) Chaperones increase association of tau protein with microtubules.  Proc. Natl. Acad. Sci. USA 100(2):721-6.

23. Gasparini, L., Netzer, W., Greengard, P., and Xu, H. (2002) Does insulin dysfunction play a role in Alzheimer's disease? Trends in Pharmacological Sciences 23(6):288-93.

24. GK Gouras, R Wang, RS Gross, MF Beal, P Greengard, H Xu. (2001) Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneuronal β-amyloid and requires mitogen-activated protein kinase signalingL Gasparini. Journal of Neuroscience 21 (8), 2561-257

25. Greenfield, JP., Tsai, J., Gouras, GK., Hai, B., Thinakaran, G., Checler, F., Sisodia, SS., Greengard, P., and Xu, H.  (1999). Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides.  Proc. Natl. Acad. Sci. USA 96(2):742-7.

26. Xu, H., Gouras, GK., Greenfield, JP., Vincent, B, Naslund, J., Mazzarelli, L, Jovanovic, J. N, Seeger, M, Relkin, NR, Liao, F., Checler, F., Buxbaum, JD, Chait, BT., Thinakaran, G., Sisodia, S., Wang, R., Greengard, P., and Gandy, S.  (1998). Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides.  Nature Medicine 4(4):447-51.

27. Xu, H., Sweeney, D., Wang, R., Thinakaran, G., Lo, A. C. Y., Sisodia, S., Greengard, P., and Gandy, S.  (1997) Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc. Natl. Acad. Sci. USA.  94(8):3748-52.

28. Xu, H., Sweeney, D., Greengard, P., and Gandy, S.  (1996). Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system.  Proc. Natl. Acad. Sci. USA. 93(9):4081-4.