师资队伍 | 鲁白,PhD

鲁白

长聘教授,博士生导师

鲁白教授于1982年在华东师范大学本科毕业。1990年获美国康乃尔(Cornel)大学医学院博士学位,师从著名神经生物学家,美国神经科学会主席Ira Black教授。1990至1993年美国洛克菲勒(Rockefeller)大学博士后,师从诺贝尔奖得主 Paul Greengard。 1993 至1996年任美国罗氏分子生物学研究所及哥伦比亚大学生物系助理教授。1996至2009年任美国国立健康研究院(NIH),儿童发育研究所神经发育研究室主任。2003至2009年任NIH精神健康研究所(NIMH)基因、认知与精神研究部(GCAP)副主任。2009年至2013年任葛兰索史克中国研发部副总裁,负责整个生物部门学战略发展决策、神经退行性疾病的药物研发,以及包括商业发展和学术合作在内的对外交流工作。2013年10月起,全职到清华大学工作,任医学院药学系教授;2016年,任清华大学药学院教授。鲁白教授长期致力于神经营养因子和突触可塑性、以及神经与精神疾病方面的研究,他是该领域具有国际知名神经生物学家。

 

研究方向

鲁白教授的实验室主要运用多种研究手段包括分子与细胞生物学,电生理,光遗传学,行为学,显微活体成像以及遗传学等,研究脑认知功能的神经环路,突触可塑性,神经与精神疾病、神经修复的分子生物学基础以及多种神经系统疾病的药物研发。重点涵盖以下几个方面:
(1)BDNF在神经退行性疾病中的基础和转化研究;
(2)神经营养因子运用于神经系统疾病的药物研究;
(3)BDNF和突触可塑性参与的高级脑功能的研究;
(4)前额皮层的认知功能研究;
(5)非人灵长类动物模型。
 

科学贡献

鲁白教授的研究兴趣涵盖神经科学与神经,精神疾病、模式动物、发育生物学、遗传学与人类基因组研究等方面,发表科学论文100多篇。他长期从事神经发育与突触可塑性的研究,有多项重要发现。
(1)1996年发现神经营养因子(BDNF)对学习记忆机制的促进作用,与国际上几位学者一起,开创了神经营养因子调控突触和神经可塑性的新领域;
(2) 2003年与Weinberger教授一起发现人BDNF基因上的一个单核甘酸变异(SNP) 能影响BDNF在脑中的释放,从而改变学习记忆功能。该工作被Science杂志列为2003年世界十大科技进展中的第二位;
(3)2004-2005年,鲁白等发现了BDNF前体proBDNF的剪切对长时记忆机制的促进作用,及proBDNF对脑中突触可塑性的抑制作用;
(4)基于BDNF和proBDNF之间的既互相对立又彼此联系的关系,鲁白教授提出了“神经营养因子作用中的阴阳机制” 假说;
(5)揭示了 “activity-dependent” 的BDNF转录所介导的神经生物学功能;
(6)发现proBDNF到BDNF的转化是神经电活动依赖性突触竞争的一种重要机制,为解决这一发育神经生物学基本问题提供了方向;
(7)提出了BDNF为基础的突触修复治疗神经退行性疾病的新策略。
 

荣誉和奖励

2014年:汤森路透集团神经科学和行为学“高被引科学家”
2007年:吴瑞奖
2006年:NIH院长奖
2003年:APAO奖
2003年:Mathilde Solowey奖
2001-2003年:Staff Recognition Award, NICHD.
1998年:白玉兰杰出科技人才奖
1989年:殷志浩大陆杰出青年科学家奖

代表性论文

Research Papers(Selected):
1. J. Guo, Y. Ji, Y. Ding, W. Jiang, Y. Sun, B. Lu (co-corresponding author) and G. Nagappan. (2016) BDNF pro-peptide regulates dendritic spines via caspase-3. Cell Death and Disease 7, e2264; doi:10.1038/cddis. 2016. 166 Published online 16 June 2016
2. P.Pang, G. Nagappan, W. Guo, B. Lu. (2016). Extracellular and intracellular cleavages of proBDNF required at two distinct stages of late-phase LTP.  npj Science of Learning. 1, 16003; doi:10.1038/npjscilearn.2016.3; published online 11 May 2016
3. W. Guo, Y. Ji, S. Wang, Y. Sun, B. Lu (2014) Neuronal activity alters BDNF- TrkB signaling kinetics and downstream functions. J. Cell Sci. 127, 2249-2260.
4. K. Sakata, K. Martinowich (co-first author), N. H. Woo, R. Schlosser, L. Shen, B. Lu (2013) Activity-dependent BDNF transcription regulates hippocampal late-phase LTP and behavioral perseverance. Proc. Natl. Acad. Sci. USA.  110(37):15103-8.
5. H. –S. Je, F. Yang, Y. Ji, G. Nagappan, B. Hempstead, and B. Lu (2012). Role of proBDNF to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses. Proc. Natl. Acad. Sci. USA.  109, 15924-15929.
6. J. Y. Kim, C. Liu, F. Zhang, X. Duan, Z. Wen, J. Song, E. Feighery, B. Lu, D. Rujescu, D. S. Clair, K. Christian, J. H. Callicott, D. R. Weinberger, H. Song and G. -l. Ming (2012) Interplay between DISC1 and GABA Signaling Regulates Neurogenesis in Mice and Risk for Schizophrenia. Cell. 5, 1051-1064.
7. K. Zheng, J. J. An, F. Yang, W. Xu, Z. Xu, J. Wu, T. Hökfelt, A. Fisahn, B. Xu, and B. Lu (2011) TrkB Signaling in Parvalbumin-Positive Interneurons Is Critical for gamma-band network synchronization in hippocampus. Proc. Natl. Acad. Sci. USA. 108, 17201-17206.
8. Y. Jiao, Z. Zhang, C. Zhang, X. Wang,  K. Sakata, B. Lu, (co-corresponding author), and Q. -Q. Sun (2011) A key mechanism underlying sensory experience-dependent maturation of neocortical GABAergic circuits in vivo. Proc. Natl. Acad. Sci. USA. 108, 12131-12136.
9. Y. Ji, Y. Lu, F. Yang, W. Shen, T. T. Tang, L. Feng, S. Duan, and B. Lu (2010) Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nature Neuroscience 13, 302-309.
10. B. Fritsch, J. Reis, K. Martinowich, H. M. Schambra, Y. Ji, L. Cohen, and B. Lu (2010) Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning. Neuron 66, 198-204.
11. T. T. Tang, F. Yang, B. Chen, Y. Lu, Y. Ji, K. Roche (co-corresponding author), and B. Lu (2009) Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. Proc. Natl. Acad. Sci. USA 106, 21395-400.
12. Y. Ji, F. Yang, F. Papaleo (co-first author), H. Wang, W. Gao, D. R. Weinberger, and B. Lu (2009) Role of dysbindin in dopamine receptor trafficking and cortical GABA function. Proc. Natl. Acad. Sci. USA 106, 19593–98.
13. S. J, Huffaker, J. Chen, K. Nicodemus, F Sambataro, F. Yang, V. Mattay, B. Lipska, T. M. Hyde, J. Song, D. Rujescu, I. Giegling, K. Mayilyan, M. J. Proust, A. Soghoyan, G. Caforio, J. H. Callicott, A. Bertolino, A. Meyer-Lindenberg, J. Chang, Y. Ji , M. Egan, T. Goldberg, K. E. Kleinman, B. Lu, D. R. Weinberger (2009) A novel, primate-specific brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nature Medicine 5, 509-518. Commented in the same issue by Horvath and Mirnics, 488-590.
14. K. Sakata, N. H. Woo, K. Martinowich, J. S. Greene, R. Schlosser, L. Shen, B. Lu (2009) Critical role f promoter-IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex. Proc. Natl. Acad. Sci. USA 106, 5942–5947.
15. G. Nagappan, E. Zaitsev, V. V. Senatorov, Jr., J. Yang, B. Hempstead, B. Lu (2009) Control of extracellular cleavage of proBDNF by high-frequency neuronal activity. Proc. Natl. Acad. Sci. USA. 106, 1267-1272. Highlights by Katherine Whalley, Nature Rev. Neuroscie. 10, 168-169.  Commented in Alzheimer Research Forum by Lucia Tapia-Arancibia as well as Margaret Fahnestock.
16. J. J. An, K. Gharami, G. –Y. Liao, N. H. Woo, A. G. Lau, F. Vanevski, E. R. Torre, K. R. Jones, Y. Feng, B. Lu, B. Xu (2008) Distinct role of long 3’UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134, 175-187.
17. X. Duan, J. H. Chang, S. Ge, R. L. Faulkner, J. Y. Kim, Y. Kitabatake, X. –b. Liu, C-H. Yang, D. Jordan, D. K. Ma, C. Y. Liu, H.-J. Cheng, G. –l. Ming, B. Lu (co-corresponding author), and H. Song (2007) Disrupted-In-Schizophrenia 1 regulates development of newly generated neurons in the adult brain. Cell. 130; 1146-1158.
18. N. H. Woo, H.K. Teng, C. –J. Siao, C. Chiaruttini, P. T. Pang, T. A. Milner, B. L. Hempstead, and B. Lu (2005) Activation of p75 NTR by proBDNF facilitates hippocampal long-term depression. Nature Neuroscience 8, 1069-1077. Highlights by Morgan Sheng, Nature. 442, 4.
19. Y. Ji, P. T. Pang, L. Feng, and B. Lu (2005) Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Nature Neuroscience. 8, 164-172. Feature article in AfCS Nature the signaling gateway, Feb, 2005, commented by Myrto Raftopoulous.
20. P. T. Pang, H. K. Teng, E. Zaitsev, N. Woo, K. Sakata, S. Zhen, K. K. Teng, W.-H. Yung, B. L. Hempstead, and B. Lu (2004) Cleavage of ProBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science. 306, 487-491. Highlights by Rachel Jones, Nature Rev. Neuroscie. 5, 898.  Commented in Sci STKE, 255 tw378. Worldwide news coverage.
21. M. F. Egan, M. Kojima, J. H. Callicott, T. E. Goldberg, B. S. Kolachana, A. Bertolino, E. Zaistev, B. Gold, D. Goldman, M. Dean, B. Lu, (co-corresponding author) and D. R. Weinberger (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257-269. With Preview by John Garbriele and Alison Preston, Cell 112, 144-145; News article by Jean Marx, Science, 299, 639-640. and Highlights by Magdalena Skipper, Nature Rev. Genetics. 4, 163.  Worldwide news coverage.
22. C. Wang, F. Yang, X. He, A. Chow, J. Du, J. Russell, and B. Lu (2001) Ca2+-binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release. Neuron  32, 99-112.
23. F. Yang, L. Feng, Z. Fang, S. W. Johnson, J. Du, L. Shen, C. -P. Wu, and B. Lu (2001) GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons.  Nature Neurosci. 4, 1071-1078.
24. F. Yang, X. He, L. Feng, K. Mizuno, X. Liu, J. Russell, W. Xiong, and B. Lu (2001) PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation.  Nature Neurosci.  4, 19-28. With News and Views comments by David Kaplan and Ellis Copper, 4, 5-7.
25. A. Figurov, L. Pozzo-Miller, T. Wang, P. Olafsson, and B. Lu (1996) Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus.  Nature  381, 706-709.           
26. P. Olafsson, T. Wang, and B. Lu (1995)  Molecular cloning and functional characterization of Xenopus Ca2+- binding protein frequenin.  Proc. Natl. Acad. Sci. USA   92, 8001-8005.
27. T. Wang, Z. Xie, and B. Lu (1995) Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses.  Nature  374, 262-266. 
28. H. G. Kim, T. Wang, P. Olafsson, and B. Lu (1994)  Neurotrophin-3 potentiates neuronal activity and inhibits g-aminobutyratergic synaptic transmission in cortical neurons.  Proc. Natl. Acad. Sci. USA  91, 12341-12345.   
29. B. Lu, W. -m. Fu, P. Greengard and M. -m. Poo (1993) Calcitonin gene-related peptide potentiates synaptic responses at developing neuromuscular junction.  Nature  363, 76-79.
30. J. Alder, .B. Lu, F. Valtorta, P. Greengard and M. -m. Poo (1992) Calcium-dependent transmitter secretion reconstituted in Xenopus oocytes: Requirement for synaptophysin. Science 257, 657-661.
31. B. Lu, P. Greengard and M. -m. Poo (1992) Exogenous synapsin I promotes functional maturation of developing neuromuscular synapses. Neuron  8, 521-529.        
32. B. Lu, M. Yokoyama, C. F. Dreyfus and I. B. Black (1991) Depolarizing stimuli regulate nerve growth factor gene expression in cultured hippocampal neurons. Proc. Natl. Acad. Sci. USA. 88, 6289-6292.      
 
Invited Reviews and Book Chapters (Selected):
1. B. Lu, G. Nagappan, X. Guan, P. J. Nathan and P. Wren (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nature Review Neuroscience. 14(6):401-16.
2. P. J. Nathan, S. R. Cobb, B. Lu, E. T. Bullmore, C. H. Davies (2011) Studying synaptic plasticity in the human brain and opportunities for drug discovery. Curr. Opin. Pharmacology. 11, 540-548.
3. B. Lu, N. H. Woo (2009) BDNF in synaptic plasticity and memory. In Encyclopedia of Neuroscience, Ed. Larry Squire. Academic Press. Oxford. Vol. 2, pp135-143.
4. B. Lu, and J. Chang (2009) Role of Neurotrophins in Neurogenesis: Functional Significance in Hippocampus-dependent Synaptic Plasticity and Memory. In “Beyond the Synapse: Cell-Cell Signaling in Synaptic Plasticity” R. D. Fields, (Ed.) Cambridge Univ. Press. pp153-159.
5. B. Lu, K. H. Wang and A. Nose (2009) Molecular mechanisms underlying neural circuit formation. Curr. Opin. Neurobiology. 19, 162-7.
6. G. Nagappan, N. H. Woo and B. Lu (2008) Ama“Zinc” link between TrkB transactivation and synaptic plasticity. Neuron, 57, 477-479.
7. K. Martinowich, H. Manji, and B. Lu (2007) New insights into BDNF function in depression and anxiety. Nature Neuroscience. 10, 1089-1093.
8. G. Nagappan, and B. Lu, (2005) Activity-dependent modulation of BDNF receptor TrkB: mechanism and implications. Trends in Neurosci. 9, 464-471.
9. B. Lu, P. T. Pang, and N. H. Woo (2005)The Yin and Yang of neurotrophin action. Nature Review Neuroscience. 8, 603-614.
10. Guhan N. and B. Lu, (2004) Homer-PIKE Complex: An novel link between mGluR1 and PI3 Kinase. Trends in Neurosci. 27, 645-648.
11. B. Lu, (2003) Pro-region of neurotrophins: Role in synaptic modulation.  Neuron. 39, 735-738.