Personal Introduction

Dr. Nan-Jie Xu received his B.S. (1994), M.S. (1997) and PhD. degree (2001) from Shengyang Pharmaceutical University. From 2001 to 2012, he completed postdoctoral training at Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and University of Texas Southwestern Medical Center. In 2012, he joined Department of Anatomy and physiology at Shanghai Jiao Tong University School of Medicine as Principal Investigator and group leader of the Laboratory of Neural Development and Brain Dysfunction.

His major research interests are receptor signaling in neuronal connections and synaptic formation, and the pathogenesis of neurological disorders.

• 1.Adult neural stem cell dormancy and reactivation

• Neural stem cells/progenitor cells and neural progenitor cells play a key role in the maintenance and renewal of neural circuits. Our works aim to clarify how adult neural stem cells transit from quiescent state to activated state, and elucidate the regulatory effect of environmental stimuli on the fate of neural stem cells.

• 2.Formation and function of neural circuits

• Our study is to clarify how long-distance neural circuits integrate external signals into cognitive and emotional nuclei in the brain and how these nuclei communicate to modulate higher neural activities such as emotion, reward, social behavior, learning and memory.

• 3. Molecular and cellular mechanisms for mental disorders

• By using the models of neurodevelopmental and neurodegenerative diseases, we investigate the key roles of Eph/ephrin receptors mediated signals, which could reveal the neural and molecular mechanisms of brain diseases.

Scientific Research Projects

• Science and Technology Innovation 2030：Neural clusters and neural circuits in brain regions associated with instinctive emotion. (2021-2026)

• National Natural Science Foundation of China: Mechanism of synaptogenesis and circuit formation for innate social behavior. (2021-2025)

• Science and Technology Commission of Shanghai Municipality: Construction and regulation of neural circuit for social behavior. (2021-2024)

• National Natural Science Foundation of China: Mechanism for early abnormal emotion representation and modulation of cognitive circuits in Alzheimer's disease. (2019-2022)

• National Natural Science Foundation of China: Mechanism for PDZ protein Lnx1 in development and plasticity of hippocampal neural circuits. (2017-2022)

• National Basic Research Program of China: Microenvironment analysis of regulating development of forebrain neural progenitor cells. (2014-2018)

• National Natural Science Foundation of China: Mechanism for EphB receptor signaling mediating neural stem cell differentiation. (2014-2017)

• National Natural Science Foundation of China: Mechanisms of Eph-ephrin receptor-mediated neural circuits related to emotion and memory. (2013-2015)

• National Natural Science Foundation of China: Eph-ephrin bidirectional signal transduction by neuronal axon splicing. (2012-2012)

Publications

1. He LN, Chen S, Yang Q, Wu Z, Lao ZK, Tang CF, Song JJ, Liu XD, Lu J, Xu XH, Chen JJ, Xu TL, Sun S*, Xu NJ*. EphB2 dependent prefrontal cortex activation promotes long-range social approach and partner responsiveness. Pro Nat Acad Sci U S A, 120(9): e2219952120 (2023)

2. Zou HY#, Guo L#, Zhang B#, Chen S, Wu XR, Liu XD, Xu XY, Li BY, Chen SD, Xu NJ*, Sun SY*. Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice. J Clin Invest, 132(8): e149160 (2022).

3. Liu XD#, Ai PH#, Zhu XN, Pan YB, Halford MM, Henkemeyer M, Feng DF, Xu TL, Sun SY*, Xu NJ*. Hippocampal Lnx1-NMDAR multi-protein complex mediates initial social memory. Mol Psychiatry, 26:3956–3969 (2021).

4. Xu M, Zhu JY, Liu XD, Luo MY, Xu NJ*. Roles of physical exercise in neurodegeneration: reversal of epigenetic clock. Transl Neurodegener, 10:30 (2021).

5. Wu XR#, Zhang Y#, Liu XD, Han WB, Xu NJ*, Sun SY*. EphB2 mediates social isolation-induced memory forgetting. Transl Psychiatry, 10:389 (2020).

6. Ai PH#, Chen S#, Liu XD, Zhu XN, Pan YB, Feng DF, Chen SD, Xu NJ*, Sun SY*. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice. Transl Neurodegener, 9:18 (2020).

7. Dong J, Pan YB, Wu XR, He LN, Liu XD, Feng DF, Xu TL, Sun SY*, Xu NJ*. A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells. Sci Adv, 5: eaav4416 (2019).

8. Liu XD, Zhu XN, Halford MM, Xu TL, Henkemeyer M, Xu NJ*. Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1. J Cell Biol, 217: 4007-4024 (2018).

9. Huang GH#, Guo L#, Zhu L, Liu XD, Sun ZL, Li HJ, Xu NJ*, Feng DF*. Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth. Cell Mol Life Sci, 75: 4207-4222 (2018).

10. Zhu XN, Liu XD, Zhuang H, Henkemeyer M, Yang JY*, Xu NJ*. Amygdala EphB2 signaling regulates glutamatergic neuron maturation and innate fear. J Neurosci, 36(39):10151-10162 (2016).

11. Zhu XN, Liu XD, Sun SY*, Zhuang H, Yang JY, Henkemeyer M, Xu NJ*. Ephrin-B3 mediates timed axon targeting and amygdala spinogenesis for innate fear behaviour. Nat Commun, 7:11096 (2016).

12. Xu NJ, Sun S, Gibson J and Henkemeyer M*. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat Neurosci, 14: 1421-1429 (2011).

13. Xu NJ, Henkemeyer M*. Ephrin-B3 reverse signaling through Grb4 and downstream cytoskeletal regulators mediates axon pruning. Nat Neurosci, 12: 268-276 (2009).

14. Xu NJ#, Yu YX#, Zhu JM, Liu H, Shen L, Zen R, Zhang X, Pei G*. Inhibition of SNAP-25 phosphorylation at Ser187 is involved in chronic morphine-induced down-regulation of SNARE complex formation. J Biol Chem, 279: 40601-8 (2004).

15. Xu NJ, Bao L, Fan HP, Bao GB, Pu L, Lu YJ, Wu CF, Zhang X, Pei G*. Morphine withdrawal increases neuronal glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J Neurosci, 23: 4775-4784 (2003).