Zhaofa Wu

The brain, the most structurally complex and functionally powerful organ in living organisms, boasts nearly 86 billion neurons in humans. Each neuron can form up to 10,000 synapses with other neurons or target cells, creating a vast and intricate network. Tools are essential for studying the complex brain, and how to develop and apply new tools for achieving breakthroughs is a major challenge in the neuroscience field. The W-lab is dedicated to combining fluorescent probe development, in vivo imaging, optogenetic/CRISPR-Cas manipulation, and chemical biology approaches to explore the communication mechanisms between brain cells and brain functions, primarily in mice. Our specific research areas include:

1)    Detecting key neural metabolites (nucleotides and lipids) and elucidating their roles in physiological processes (such as sleep and emotion) and pathological processes (such as epilepsy and stroke).

2)    Investigating the energy metabolism patterns and regulatory mechanisms of different cell types in the brain.

3)    Probing the communication between neural, tumor, and immune systems.

The W-lab is currently recruiting associate researchers, assistant researchers, postdoctoral researchers (special research assistants), PhD students, and visiting graduate students. Welcome ambitious young people interested in neuroscience to join us (email: wuzhaofa@genetics.ac.cn).

1. Wei, Q.#, Bai, Z.#, Wang, L.#, ... Li, Y.*, Wu, Z.*, & Wang, J.* (2025). A high-performance fluorescent sensor spatiotemporally reveals cell-type specific regulation of intracellular adenosine in vivo. Nature Communications, 16(1), 1-18.

 

2. Zhou, X.#, He, Y.#, Xu, T.#, Wu, Z.#, Guo, W., Xu, X., ... & Chen, J. F.* (2024). 40 Hz light flickering promotes sleep through cortical adenosine signaling. Cell Research, 1-18.

 

3. Wu, Z.#, Cui, Y.#, Wang, H.#, …, Xu, M., Luo, M.* & Li, Y.* (2023), Neuronal activity-induced, ENT-dependent, somatodendritic adenosine release revealed by a GRAB sensor. PNAS, 120(14), e2212387120.

 

4. Wu, Z.*, He, K., Chen, Y., …, Du, J., Jing, M., & Li, Y.* (2022). A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo. Neuron, 110, 770-782 e775.

—Selected as the “Best of Neuron 2021-2022”.

 

5. Wu, Z., Lin, D., & Li, Y.* (2022), Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience, 23, 257–274 (Invited Review).

 

6. Peng, W.#, Wu, Z.#, Kun, S.#, Zhang, S., Li, Y. & Min, X.* (2020). Regulation of sleep homeostasis mediator adenosine by basal forebrain glutamatergic neurons. Science, 369, 1208.

—Highlights by Whalley K., Nature Reviews Neuroscience. 2020 Nov;21(11):593-593.

 

7. Wu, Z.*, & Li, Y.* (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience Research, 35-43. (Cover Review).

 

8. Wu, Z.#, Feng, J.#, Jing, M., & Li, Y.* (2019). G protein-assisted optimization of GPCR-activation based (GRAB) sensors. Neural Imaging and Sensing 2019, vol. 10865, p. 108650N. International Society for Optics and Photonics.

 

9. Xin, Q.#, Wang, J.#, …, Wu, Z, …, Hu, H.* (2025). Neuron-astrocyte coupling in lateral habenula mediates depressive-like behaviors. Cell.

 

10. Park, G.#, Lee, G.#, …, Wu, Z., Li, Y., & Choi M.* (2025). Glia-like taste cells mediate an intercellular mode of peripheral sweet adaptation. Cell, 188(1), 141-156

 

11. Zhang, Z.#, Wang, Y.#, ... Wu, Z., & Qin, W.* (2025). Spatiotemporally-resolved mapping of extracellular proteomes via in vivo-compatible TyroID. Nature Communications, 16, 2553

 

12. Li, H., Zhao, Y., …, Wu, Z., Li, Y., & Luo, M.* (2024). Astrocytes release ATP/ADP and glutamate in flashes via vesicular exocytosis. Molecular Psychiatry, 1-15.

 

13. Umpierre, A. D.#, Li, B.#, …, Wu, Z., ... & Wu, L.* (2024). Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis. Neuron, 112(12), 1959-1977.

 

14. Chen, Y.#, Luan, P.#, Liu, J.#, …, Wu, Z., & Jing, M.* (2024). Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice. Nature Neuroscience, 1-12.

 

15. Berki, P.#, Cserép, C.#, Környei, Z.#, …, Wu, Z., ... & Dénes, Á.* (2024). Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices. Nature Communications, 15(1), 5402.

 

16. Roy, K.#, Zhou, X.#, Otani, R.#, Yuan, P. C.#, …, Wu, Z., ... & Lazarus, M.* (2024). Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors. Nature Communications, 15(1), 3661.

 

17. Bayazitov, I. T., Teubner, B. J., Feng, F., Wu, Z., Li, Y., Blundon, J. A., & Zakharenko, S.* (2024). Sound-evoked adenosine release in cooperation with neuromodulatory circuits permits auditory cortical plasticity and perceptual learning. Cell Reports, 43(2).

 

18. Ji, E., Zhang, Y., Li, Z., Wei, L., Wu, Z., Li, Y., Yu, X.*, & Song, T. J.* (2024). The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking. Neuroscience Bulletin, 1-18.

 

19. Peng, W.#*, Liu, X.#, Ma, G.#, Wu, Z., … Zhang, S.*, & Min, X.* (2023). Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity. Cell Discovery, 9(1), 16.

 

20. Li, X., Li, Y., Zhou, Y., …, Wu, Z., ... & Dai, Q.* (2023). Real-time denoising of fluorescence time-lapse imaging enables high-sensitivity observations of biological dynamics beyond the shot-noise limit. Nature Biotechnology, 41, 282–292.

 

21. Hatashita, Y., Wu, Z., …, & Inoue, T.* (2023). Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses. Glia, 71(9), 2250-2265.

 

22. Lin, R.#*, Zhou, Y.#, Yan, T.#, Wang, R.#, Li, H., Wu, Z., ... & Luo, M.* (2022). Directed evolution of adeno-associated virus for efficient gene delivery to microglia. Nature Methods, 1-10.

 

23. Pittolo, S., Yokoyama, S., Willoughby, D., ... Wu, Z., … & Poskanzer, K.* (2022). Dopamine Activates Astrocytes in Prefrontal Cortex via α1-Adrenergic Receptors. Cell Reports, 40.

 

24. Roberts, B., Lambert, E., Livesey, J., Wu, Z., Li, Y. & Cragg, S.* (2022). Dopamine release in nucleus accumbens is under tonic inhibition by adenosine A1 receptors regulated by astrocytic ENT1 and dysregulated by ethanol. The Journal of Neuroscience, 42, 1738-1751.

 

25. Lu, C.#, Ren, J.#, Mo J., …, Wu, Z., Li, Y., Gao, T., Cao, X.* (2022). Glucocorticoid receptor-dependent astrocytes mediate stress vulnerability. Biological Psychiatry, 92(3), 204-215.

 

26. Dai, R., Yu, T., Weng, D., Li, H., Cui, Y., Wu, Z., ... & Luo, M.* (2022). A neuropsin-based optogenetic tool for precise control of Gq signaling. Sci. China Life Sci., 1-14.

 

27. Qian, C., Wu, Z.#, Sun, R.#, …, & Li, Y.* (2021). Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose. eLife, 10, e65417.

 

28. Wang, Q.#, Kong, Y.#, Wu, D. Y., ..., Wu, Z., Li, Y., Yang, J.*, & Gao, T.* (2021). Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice. Nature Communications, 12(1), 1-13.

 

29. Feng, J., Zhang, C., Lischinsky, J. E., …, Wu, Z., ... Lin, D., Du, J., & Li, Y.* (2019). A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine. Neuron, 102(4), 745-761.

 

30. Yu, H., Zhao, T., Liu, S., Wu, Q., Johnson, O., Wu, Z., …, Lei, X., Luo, W.* & Li, Y.* (2019). MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife, 8, e48431.

 

31. Guo, Q. #, Hou, T.#, Xie, W.#, ... Wu, Z., … & Wang, S.* (2024). Calcium Homeostasis Modulator 2 Constitutes an ATP-regulation Pore in Mitochondria. bioRxiv, 2024-09.