研究中(zhōng)心 - 江門市新會區威信高技術科學研究所

張旭

研究員(yuán)，研究組組長，博士生(shēng)導師

Email：xu.zhang@@gdiist.cn

個人簡介：

張旭，神經科學家，中(zhōng)國科學院院士，發展中(zhōng)國家科學院院士，中(zhōng)國醫學科學院學部委員(yuán)。1994年7月在瑞典卡羅琳斯卡醫學院神經科學系獲博士學位。1994年先後在第四軍醫大(dà)學神經科學研究所任講師、副教授和研究員(yuán)、神經科學研究所副所長。1999年12月任中(zhōng)國科學院上海生(shēng)命科學研究院神經科學研究所研究員(yuán)、感覺系統研究組組長。2021年2月任中(zhōng)國科學院上海高等研究院研究員(yuán)，2021年3月任上海腦-智工(gōng)程中(zhōng)心主任，2021年6月任江門市新會區威信高技術科學研究所院長。兼任中(zhōng)國神經科學學會理事長、中(zhōng)國細胞生(shēng)物(wù)學學會副理事長、中(zhōng)華醫學會疼痛分(fēn)會副主任委員(yuán)，上海腦-智工(gōng)程中(zhōng)心理事長等職。

軀體(tǐ)感覺神經網絡研究組：

本研究組主要從事軀體(tǐ)感覺的神經網絡研究。軀體(tǐ)感覺包括了痛、癢、溫度等感覺，背根節的初級感覺神經元是軀體(tǐ)感覺傳入的第一(yī)站，其外(wài)周支投射到皮膚、肌肉等組織，感受外(wài)界的痛、癢、溫度等信息，其中(zhōng)樞支投射到脊髓，再經大(dà)腦的不同區域傳向大(dà)腦皮層，從而實現軀體(tǐ)感覺的感受。我(wǒ)(wǒ)們以往的研究發現了成纖維細胞生(shēng)長因子13（FGF13）和内源性鈉鉀泵激動劑濾泡素抑制素樣蛋白(bái)1（FSTL1）等新的痛覺信息調控系統，爲臨床鎮痛及藥物(wù)研發提供了新的理論基礎。近年來，我(wǒ)(wǒ)們發展了背根節初級感覺神經元的單細胞測序技術，對初級感覺神經元進行了新的分(fēn)類，确定了一(yī)些标記性分(fēn)子，建立了細胞類群與在體(tǐ)功能的相互關系。目前我(wǒ)(wǒ)們緻力于發現各類群初級感覺神經元對痛、癢等軀體(tǐ)感覺調制具有重要意義的感覺神經傳遞網絡，研究中(zhōng)樞神經系統中(zhōng)痛、癢等軀體(tǐ)感覺神經網絡的交互作用。

外(wài)周神經損傷和持續炎症可以引起病理性痛，早期我(wǒ)(wǒ)們在實驗室發展了來自大(dà)鼠背根節的 cDNA 微陣列技術，系統性地闡述了慢(màn)性痛的背根節和脊髓基因表達譜，發現在外(wài)周神經損傷後背根節和脊髓背角中(zhōng)離(lí)子通道、受體(tǐ)和信号轉導分(fēn)子的基因表達發生(shēng)了顯著的變化，爲外(wài)周神經損傷後引起背根節和脊髓背角獨特的基因表達譜提供了證據。2021年我(wǒ)(wǒ)們利用單細胞測序技術進一(yī)步揭示了神經損傷導緻的神經病理性痛引起的初級感覺神經元細胞類群的變化以及相應的功能改變。目前我(wǒ)(wǒ)們緻力于發現神經病理性痛發生(shēng)時的神經環路結構改變，并揭示其與神經病理性痛發生(shēng)的相關性，解析其對認知(zhī)等大(dà)腦功能的影響及環路機制。

代表論著：

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.

張旭