Principal Investigator

黄卓
脑疾病的离子通道机制、癫痫病、抑郁症、离子通道药物筛选

联系电话:
通信地址: 北京市海淀区学院路38号北京大学医学部医学科技楼1501,邮编100191
电子邮件:huangz@hsc.pku.edu.cn

 

研究兴趣:

神经元微小结构中(树突、轴突、树突棘和轴突起始段等)离子通道的表达、分布与功能。神经元的兴奋性取决于细胞表面离子通道的亚细胞分布、表达数量及其生物物理学特征。神经细胞兴奋性失常会导致许多神经或精神系统疾病,如癫痫病,抑郁症,神经痛等。本研究组主要利用膜片钳电生理技术,结合生物化学、分子生物学、药理学等方法,揭示离子通道在不同亚细胞结构中的表达水平及其生理学功能,探索其在特定神经精神系统疾病中的病理学变化,并开展基于离子通道靶标的活性化合物筛选工作。

 

代表性科研论文:

 

  1. Yuan T, Wang YF, Jin YC, Xu S, Zhang H, Chen Q, Li N, Ma XY, Song HF, Peng C, Yang H, Geng Z, Dong J, Duan GF, Sun Q, Yang Y, Yang F, Huang Z* (2023) Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development. eLife. 12:RP87559
  2. Fan MH, Liu YQ, Shang YF, Xue YX, Liang J, Huang Z* (2022) JADE2 is essential for hippocampal synaptic plasticity and cognitive, Biological Psychiatry. 2022 Nov 15;92(10):800-814.
  3. Liu YQ, Li MH, Fan MH, Song Y, Yu HJ, Zhi XJ, Xiao K, Lai SR, Zhang JL, Jin XQ, Shang YF, Liang J*, and Huang Z* (2019) CDYL-mediated histone crotonylation regulates stress-induced depressive behaviors, Biological Psychiatry, 85(8):635-649
  4. Liu YQ, Lai SR, Ma WN, Ke W, Zhang C, Liu SM, Zhang Y, Pei F, Li SY, Yi M, Shu YS, Shang YF, Liang J*, and Huang Z* (2017) CDYL suppresses epileptogenesis through repression of axonal Nav1.6 sodium channel expression. Nature Communications, 8(1):355.
  5. Gao, Y., Xu, S., Cui, X., Xu H., Qiu Y., Wei Y., Dong Y., Zhu B., Peng C., Liu S., Zhang X., Sun J., Huang Z*, Zhao Y. (2023) Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3.  Nature Communications. 14, 516 (2023). https://doi.org/10.1038/s41467-023-36260-2
  6. Qu Y, Lu Y, Zhang D, Liu X, Fan P, Chen J, Zhang H, Yang K, Tian T, Zhou Y, Zhang Q, Zhang Y, Wang L, Huang Z*, Liu Y*, Hu A*, Zhou X*. (2023) Identification of a novel frameshift mutation in the SCNN1B causing Liddle syndrome. Science Bulletin (Beijing). 2023 Feb 7:S2095-9273(23)00091-9. doi: 10.1016/j.scib.2023.02.006. Epub ahead of print. PMID: 36774301.
  7. Li Y., Yuan T., Huang B., Zhou F., Peng C., Li X., Qiu Y., Yang B., Zhao Y., Huang Z.*, and Jiang D.* (2023) Structure of human NaV1.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin. Nature Communications.
  8. Zhang J, Shi Y, Fan J, Chen H, Xia Z, Huang B, Jiang J, Gong J, Huang Z*, Jiang D*. (2022) N-type fast inactivation of a eukaryotic voltage-gated sodium channel. Nature Communications. 2022 May 17; 13(1):2713.
  9. Zhang ZL, Chen HW, Geng Z, Yu ZY, Li H, Dong YL, Zhang HW, Huang Z*, Jiang JQ*, Zhao Y* (2022) Structural basis of ligand binding modes of human EAAT2, Nature Communications. Jun 9;13(1):3329.
  10. Dong Y, Gao Y, Xu S, Wang Y, Yu Z, Li Y, Li B, Yuan T, Yang B, Zhang XC, Jiang D*, Huang Z*, Zhao Y*. (2021) Closed-state inactivation and pore-blocker modulation mechanisms of human CaV2.2. Cell Rep. Nov 2;37(5):109931.
  11. Li Z, Cai G, Fang F, Li W, Fan M, Lian J, Qiu Y, Xu X, Lv X, Li Y, Zheng R, Wang Y, Li Z, Zhang G, Liu Z, Huang Z*, Zhang L*. Discovery of Novel and Potent Methyl-d-aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models (2021). J Med Chem. 13;64(9):5551-5576.
  12. Zhang J, Zhang C, Chen X, Wang B, Ma W, Yang Y, Zheng R*, Huang Z* (2021) PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice. Communication Biology, 4(1):263.
  13. Ma Y, Xie H, Du X, Wang L, Jin X, Zhang Q, Han Y, Sun S, Wang L, Li X, Zhang C, Wang M, Li C, Xu J, Huang Z*, Wang X*, Chai Z*, Deng H*. (2021) In vivo chemical reprogramming of astrocytes into neurons. Cell Discovery 7(1):12.
  14. Kong W, Tu X, Huang W, Yang Y, Xie Z* & Huang Z * (2020) Prediction and Optimization of NaV1.7 Sodium Channel Inhibitors Based on Machine Learning and Simulated Annealing. Journal of chemical information and modeling, 60(6), 2739–2753.
  15. Chi XM, Jin XQ, Chen Y, Lu XL, Tu XY, Li XR, Zhang YY, Lei JL, Huang J, Huang Z*, Zhou Q* and Pan XJ* (2020) Structural insights into the gating mechanism of human SLC26A9 mediated by its C-terminal sequence, Cell Discovery, 6:55
  16. Yang L, Liu Y, Fan M, Zhu G, Jin H, Liang J, Liu Z, Huang Z*, Zhang L* (2019) Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL, Eur J Med Chem., 15;182:111656
  17. Huang Z, Lujan R, Kadurin I, Uebele VN, Renger JJ, Dolphin AC, Shah MM. (2011) Presynaptic HCN1 channels regulate Ca(V)3.2 activity and neurotransmission at select cortical synapses, Nature Neuroscience, 14(4):478-86 
  18. Huang Z, Lujan R, Martinez-Hernandez J, Lewis AS, Chetkovich DM, Shah MM. (2012) TRIP8b-Independent Trafficking and Plasticity of Adult Cortical Presynaptic HCN1 Channels. Journal of Neuroscience, 32(42):14835-48. 
  19. Huang Z, Walker MC, Shah MM. (2009) Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis, Journal of Neuroscience, 29(35):10979-88. 

 

实验室网站:

http://dmcp.sps.bjmu.edu.cn/szdw_20180115155901250603/tpyjy_20180115155901250603/192175.htm