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Bai LU, Ph.D.

Dr. Bai Lu is currently a tenured Professor in the School of Pharmaceutical Sciences at Tsinghua University. After postdoctoral training with the Nobel laureate Paul Greengard at Rockefeller Univ., Dr. Lu became an Assistant Professor at Roche Institute of Molecular Biology/Columbia Univ. He joined National Institutes of Health (NIH) in 1996, and became the Chief of the Neural Development and Plasticity Section in 2001 (tenured). In 2004, he was named the Associate Director of Gene, Cognition and Psychosis Program (GCAP), the largest translational medicine program at NIH at that time. Dr. Lu was recruited to the GlaxoSmithKlein (GSK) R&D Center as the vice president in China in July, 2009. In Oct., 2013, Dr. Lu became a professor of Department of Pharmacology and Pharmaceutical Science, and the Executive Vice Dean, in charge of Tsinghua Univ. Medical School, until Jan. 2016.

  • Research Interests

  • Scientific Contributions

  • Honors and Awards

  • Selected Publications

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.

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.

  • 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.

Research Papers(Selected):

1. H. Liu, F. Mei, R. Ye, S. Wang, Y. Ding, X. Han, Y. Zhi, K. Pang, B. Lu (2024) APOE3ch alleviates Aβ and tau pathology and neurodegeneration in the human APPNL-G-F cerebral organoid model of Alzheimer’s disease. Cell Res. 34(6):451-454. doi: 10.1038/s41422-024-00957-w.

2. F. Mei, C. Zhao, S. Li, Z. Xue, Y. Zhao, Y. Xu, R. Ye, H. You, P. Yu, X. Han, G. Carr, D. R. Weinberger, F. Yang, B. Lu (2024) Ngfr+ cholinergic projection from SI/nBM to mPFC selectively regulates temporal order recognition memory. Nature Communication. 15(1):7342. doi: 10.1038/s41467-024-51707-w.

3. F. Yang, H. You, T. Mizuia, (co-first author), K. Kiyosuea, K. Takao, T. Miyakawa, X. Li, T. Bai, K. Xia, L. Zhang, D. Pang, Y. Xu, C. Zhu, M. Kojima, B. Lu (2024) Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo. Mol. Psychiatry. doi: 10.1038/s41380-024-02595-5.

4. F. W. Pun, B. H. M Liu, X. Long, J. D. Rothstein, M. E. Cudkowicz, I. V. Ozerov, H. W. Leung, G. H. D. Leung, A. Shneyderman, J. Wang, F. Ren, A. Aliper, X. Guan, B. Lu (co-corresponding author), A. Zhavoronkov, (2022) Identification of therapeutic targets and drug repurposing candidates for amyotrophic lateral sclerosis using PandaOmicsTM – an AI-enabled biological target discovery platform. Frontier in Aging Neuroscie. 14: 914017.

5. X. Qin, Y. Zhao, Y. Xu, T. Zhang, C. Yin. J. Qiao, W. Guo, B Lu (2022) TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice. Nature Communication. 13(1): 914.

6. K. Pang, R. Jiang, W. Zhang, Z. Yang, L. Li, M. Shimozawa, S. Tambaro, J. Mayer, B. Zhang, M. Li, J. Wang, H. Liu, A. Yang, X. Chen, J. Liu, B. Winblad, H. Han, T. Jiang, W. Wang, P. Nilsson, W. Guo, B. Lu (2021) An App knock-in rat model for Alzheimer’s disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments. Cell Research. 32(2): 157–175.

7. J. Liu, Q. Chen, S. Yang, Y. Li, Y. Dou, Y-Q. Deng, J. Bi, Y. Tan, H. Wang, W. Gong, X. Xu, Z. Li, G. Lang, C-F. Qin, B. Lu (co-corresponding author), W. Jiang (2021) hACE2 Fc-neutralization antibody cocktail provides synergistic protection against SARS-CoV-2 and its spike RBD variants. Cell Discovery. 7(1):54.

8. S. Wang, H. Yao, Y. Xu, R. Hao, W. Zhang, H. Liu, Y. Huang, W. Guo, B. Lu (2020). Therapeutic potential of a TrkB agonist antibody for Alzheimer’s disease. Theranostics. 10: 6854-6874.

9. W. Guo, Y. Chen, K. Pang, H. Li, S. Wang, H. Yao1, Y. Xu, H. Liu, V. Lopes-Rodrigues, W. Wu, B. Lu (2019). TrkB agonist antibodies with unique properties superior to BDNF: Utility in treating motoneuron degeneration. Neurobiology of Diseases. 132：104590.[bl1]

10. F. Han, X. M. Guan, W. Guo, B. Lu (2019) Therapeutic potential of a TrkB agonistic antibody for ischemic brain injury. Neurobiology of Diseases. 127:570-581.

11. 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(6):e2264
12. 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.
[bl2] 13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.          
36. 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 .
37. T. Wang, Z. Xie, and B. Lu (1995) Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses.  Nature  374, 262-266.
38. 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.  
39. 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.
40. 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.
41. B. Lu, P. Greengard and M. -m. Poo (1992) Exogenous synapsin I promotes functional maturation of developing neuromuscular synapses. Neuron  8, 521-529.        
42. 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.



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