张旭

研究员,研究组组长,博士生导师

Email:xu.zhang@@gdiist.cn

个人简介:

张旭,神经科学家,中国科学院院士,发展中国家科学院院士,中国医学科学院学部委员。1994年7月在瑞典卡罗琳斯卡医学院神经科学系获博士学位。1994年先后在第四军医大学神经科学研究所任讲师、副教授和研究员、神经科学研究所副所长。1999年12月任中国科学院上海生命科学研究院神经科学研究所研究员、感觉系统研究组组长。2021年2月任中国科学院上海高等研究院研究员,2021年3月任上海脑-智工程中心主任,2021年6月任广东省智能科学与技术研究院院长。兼任中国神经科学学会理事长、中国细胞生物学学会副理事长、中华医学会疼痛分会副主任委员,上海脑-智工程中心理事长等职。

躯体感觉神经网络研究组:

本研究组主要从事躯体感觉的神经网络研究。躯体感觉包括了、痒、温度等感觉,背根节的初级感觉神经元是躯体感觉传入的第一站,其外周支投射到皮肤、肌肉等组织,感受外界的痛、痒、温度等信息,其中枢支投射到脊髓,再经大脑的不同区域传向大脑皮层,从而实现躯体感觉的感受。我们以往的研究发现了成纤维细胞生长因子13(FGF13)和内源性钠钾泵激动剂滤泡素抑制素样蛋白1(FSTL1)等新的痛觉信息调控系统,为临床镇痛及药物研发提供了新的理论基础。近年来,我们发展了背根节初级感觉神经元的单细胞测序技术,对初级感觉神经元进行了新的分类,确定了一些标记性分子,建立了细胞类群与在体功能的相互关系。目前我们致力于发现各类群初级感觉神经元对痛、痒等躯体感觉调制具有重要意义的感觉神经传递网络,研究中枢神经系统中痛、痒等躯体感觉神经网络的交互作用。

外周神经损伤和持续炎症可以引起病理性痛,早期我们在实验室发展了来自大鼠背根节的 cDNA 微阵列技术,系统性地阐述了慢性痛的背根节和脊髓基因表达谱,发现在外周神经损伤后背根节和脊髓背角中离子通道、受体和信号转导分子的基因表达发生了显著的变化,为外周神经损伤后引起背根节和脊髓背角独特的基因表达谱提供了证据。2021年我们利用单细胞测序技术进一步揭示了神经损伤导致的神经病理性痛引起的初级感觉神经元细胞类群的变化以及相应的功能改变。目前我们致力于发现神经病理性痛发生时的神经环路结构改变,并揭示其与神经病理性痛发生的相关性,解析其对认知等大脑功能的影响及环路机制。

代表论著:

1. Chen Y., Song Y-R., Wang H-D., Zhang Y-Y., Hu Y., Wang K-K., Lu Y-J., Zhang Z., Li S., Li A., Bao L., Xu F-Q., Li C-L., and Zhang X. (2022) Distinct neural networks derived from galanin-containing nociceptors and neurotensin-expressing pruriceptors. PNAS, 119: e2118501119.

2. Zhang S., Cai B., Li Z., Wang K-K., Bao L., Li C-L., and Zhang X. (2022) Fibroblastic SMOC2 suppresses mechanical nociception by inhibiting coupled activation of primary sensory neurons. J. Neurosci. 42: 4069-4086.

3. Wu D., Chen Y., Li Z., Xie H., Wang S-S., Lu Y-J., Bao L., Zhang X., and Li C-L. (2022) Zcchc12-containing nociceptors are required for noxious heat sensation. J. Neurosci. 42: 2690-2700.

4. Pan X-Y., Zhao J-R., Zhou Z-Y., Chen J-J., Yang Z-X., Wu Y-X., Bai M-Z., Jiao Y, Yang Y, Hu X-Y., Cheng T-L., Lu Q-Y., Wang B, Li C-L, Lu Y-J, Diao L, Zhong Y-Q, Pan J, Zhu J-M., Xiao H-S, Qiu Z-L, Li J, Wang Z-F., Hui J-Y., Bao L, Zhang X. (2021) 5’-UTR SNP of FGF13 causes translational defect and intellectual disability. eLife, 10: e63021.

5. Wang K-K., Wang S-S., Chen Y., Wu D., Hu X-Y., Lu Y-J., Wang L-P., Bao L., Li C-L., and Zhang X. (2021) Single-Cell Transcriptomic Analysis of Somatosensory Neurons Uncovers Temporal Development of Neuropathic Pain. Cell Res., doi: 10.1038/s41422-021-00479-9.

6. Dong F., Shi H-X., Yang L., Xue H-Q., Wei M-Y., Zhong Y-Q., Bao L., and Zhang X. (2020) FGF13 is required for histamine-induced itch sensation by interaction with NaV1.7. J. Neurosci. 40: 9589-9601.

7. Li J-Y., Shi H-X., Liu H., Dong F., Liu Z-P., Lu Y-J., Chen L-N., Bao L., and Zhang X. (2020) Nerve Injury-Induced Neuronal PAP-I Maintains Neuropathic Pain by Activating Spinal Microglia. J. Neurosci., 40: 297–310.

8. Yang L., Dong F., Yang Q., Yang P-F., Wu R., Wu Q-F., Wu D., Li C-L., Zhong Y-Q., Lu Y-J., Cheng X., Xu F-Q., Chen L., Bao L., and Zhang X. (2017) FGF13 selectively regulates heat nociception by interacting with Nav1.7. Neuron, 93: 806-821.

9. Li C-L., Li K-C., Wu D., Chen Y., Luo H., Zhao J-R., Wang S-S., Sun M-M., Lu Y-J., Zhong Y-Q., Hu X-Y., Hou R., Zhou B-B., Bao L., Xiao H-S., and Zhang X. (2016) Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity. Cell Res., 26: 83-102.

10. Liu H., Wu Q-F., Li J-Y., Liu X-J., Li K-C., Zhong Y-Q., Wu D., Wang Q., Lu Y-J., Bao L., and Zhang X. (2015) Fibroblast growth factor 7 is a nociceptive modulator secreted via large dense-core vesicles. J. Mol. Cell Biol., 7: 466-475.

11. Wang F., Cai B., Li K-C., Hu X., Lu Y., Wang Q., Bao L., and Zhang X. (2015) FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation. Cell Res., 25: 318-334.

12. Zhang X., Bao L., Li S. (2015) Opioid receptor trafficking and interaction in nociceptors. Br. J. Pharmacol., 172: 364–374. (Review)

13. Wu Q-F., Yang L., Li S., Wang Q., Yuan X-B., Gao X., Bao L., and Zhang X. (2012) Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration. Cell, 149: 1549-1564. 

14. Liu X-J., Zhang F-X., Liu H., Li K-C., Lu Y-J., Wu Q-F., Li J-Y., Wang B., Wang Q., Lin L-B., Zhong Y-Q., Xiao H-S., Bao L., and Zhang X.(2012)Activin C expressed in nociceptive afferent neurons is required for suppressing inflammatory pain. Brain, 135: 391-403. 

15. Li K-C., Wang F., Zhong Y-Q., Lu Y-J., Wang Q., Zhang F-X., Xiao H-S., Bao L., and Zhang X. (2011) Reduction of follistatin-like 1 in primary afferent neurons contributes to neuropathic pain hypersensitivity. Cell Res., 21: 697-699.

16. Li K-C., Zhang F-X., Li C-L., Wang F., Yu M-Y., Zhong Y-Q., Zhang K-H., Lu Y-J., Wang Q., Ma X-L., Yao J-R., Wang J-Y., Lin L-B., Han M., Zhang Y-Q., Kuner R., Xiao H-S., Bao L., Gao X., and Zhang X. (2011) Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase. Neuron, 69: 974-987.

17. Zhao B., Wang H-B., Lu Y-J., Hu J-W., Bao L., and Zhang X. (2011) Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles. Cell Res., 21: 741-753.

18. He S-Q., Zhang Z-N., Guan J-S., Liu H-R., Zhao B, Wang H-B., Li Q., Yang H., Luo J., Li Z-Y., Wang Q., Lu Y-J., Bao L., and Zhang X. (2011) Facilitation of μ-opioid receptor activity by preventing δ-opioid receptor-mediated codegradation. Neuron, 69: 120-131.

19. Zhang F-X., Liu X-J., Gong L-Q., Yao J-R., Li K-C., Li Z-Y., Lin L-B., Lu Y-J., Xiao H-S., Bao L., Zhang X-H., and Zhang X. (2010) Inhibition of inflammatory pain by activating B-Type natriuretic peptide signal pathway in nociceptive sensory neurons. J. Neurosci., 30: 10927-10938.

20. Wang H-B., Zhao B., Zhong Y-Q., Li K-C., Li Z-Y., Wang Q., Lu Y-J., Zhang Z-N., He S-Q., Zheng H-C., Wu S-X., Hökfelt T-G., Bao L., and Zhang X. (2010) Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons. Proc. Natl. Acad. Sci. USA, 107: 13117-13122.

21. Zhang X., Bao L., and Ma G-Q. (2010) Sorting of neuropeptides and neuropeptide receptors into secretory pathway. Prog. in Neurobiol., 90: 276-283. (Review)

22. Zhang X., Bao L., and Guan J-S. (2006) Role of delivery and trafficking of δ-opioid peptide receptors in opioid analgesia and tolerance. Trends in Pharmacol. Sci., 27: 324-329. (Review)

23. Zhang X. and Bao L. (2006) The development and modulation of nociceptive circuitry. Curr. Opin. Neurobiol., 16: 460-466 (Review)

24. Guan J-S., Xu Z-Z., Gao H., He S-Q., Ma G-Q., Sun T., Wang L-H., Zhang Z-N., Lena I., Kitchen I., Elde R., Zimmer A., He C., Pei G., Bao L. and Zhang X. (2005) Interaction with vesicle luminal protachykinin regulates surface expression of δ-opioid receptors and opioid analgesia. Cell, 122: 619-631.

25. Zhang X. and Xiao H-S. (2005) Gene array analysis to determine the components of neuropathic pain signaling. Curr. Opin. Mol. Ther., 7: 532-537. (Review)

26. Yang L., Zhang F-X., Huang F., Lu Y-J., Li G-D., Bao L., Xiao H-S., and Zhang X. (2004) Peripheral axotomy induces trans-synaptic modification of channels, receptors and signaling pathways in rat dorsal spinal cord. Eur. J. Neurosci., 19: 871-883.

27. Bao L., Jin S-X., Zhang C., Wang L-H., Xu Z-Z., Zhang F-X., Wang L-C., Ning F-S., Cai H-J., Guan J-S., Xiao H-S., Xu Z-Q., He C., Hökfelt T., Zhou Z., and Zhang X. (2003) Activation of delta-opioid receptors induces receptor insertion and neuropeptide secretion. Neuron, 37: 121–133.

28. Xiao H-S., Huang Q-H., Zhang F-X., Bao L., Lu Y-J., Guo C., Yang L., Huang W-J., Fu G., Xu S-H., Cheng X-P., Yan Q., Zhu Z-D., Zhang X., Chen Z., Han Z-G., and Zhang X. (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc. Natl. Acad. Sci. USA., 99: 8360-8365.

29. Bao L., Wang H-F., Cai H-J., Tong Y-G., Jin S-X., Lu Y-J., Grant G., Hökfelt T., and Zhang X. (2002) Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur. J. Neurosci., 16: 175-185.

30. Tong Y-G., Wang H-F., Ju G., Grant G., Hökfelt T., and Zhang X. (1999) Increased uptake and transport of cholera toxin B-subunit in dorsal root ganglion neurons after peripheral axotomy: possible implications on sensory sprouting. J. Comp. Neurol., 404: 143-158. 



张旭研究组