Research Interests
Dr. Lu's current research focuses on neural circuits underlying cognitive functions，neurodegenerative and psychiatric diseases, translational medicine, molecular pathways underlying synaptic function and neural repairs. A variety of approaches, including cellular and molecular, electrophysiological, optogenetics，behavioral, imaging and genetics, are being used.
(1) Basic and translational research of BDNF in neurodegenerative diseases.
(2) Drug discovery and development with neurotrophin in nervous system diseases.
(3) BDNF and synaptic plasticity in high brain functions.
(4) The cognitive functions of prefrontal cortex.
(5) Non-human primate models.
Scientific Contributions
Dr. Bai Lu pioneered research in the role of neurotrophins in synapse development and plasticity, and is credited for several major discoveries:
1) discovery of BDNF regulation of LTP, a cellular model for memory;
2) identification of a SNP that impacts BDNF secretion and short-term memory in human;
3) elucidation extracellular cleavage of proBDNF to mature BDNF and its role in long-term synaptic plasticity;
4) demonstration of the opposing roles of proBDNF and mature BDNF in synaptic plasticity, leading to a "Yin-Yang" hypothesis of neurotrophin actions;
5) revealing the functional role of activity-dependent BDNF transcription;
6）discovery of proBDNF to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses.
7) raising the therapeutic strategy of "BDNF-based synaptic repair" for neurodegenerative diseases.
Honors and Awards
Thomson Reuters "World's Highly Cited Researcher", Neuroscience and Behavior, 2014
Ray Wu Award, 2007
NIH Director's Mentoring Award, 2006
APAO Award for Outstanding Achievement, 2003
Mathilde Solowey Award in the Neurosciences. 2003
Staff Recognition Award, NICHD. 2001, 2002, 2003.
White Magnolia Award for outstanding contributions to the advancement of science in China. Shanghai, China. 1998.
1996 NIH Director's Lecturer Award
"Yin Zhihao Award" for outstanding Mainland Chinese Scientists in America. 1989. The first delegation of Chinese scientists to visit Taiwan.
Selected Publications
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) Ca
2+-binding protein frequenin mediates GDNF-induced potentiation of Ca
2+ 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 Ca
2+- 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.
