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黄卓

 

 

【个人介绍】

黄卓研究员,博士生导师,中组部青年拔尖人才,教育部新世纪人才,现任北京大学药学院副院长,兼任药理系党支部书记,中国药理学会理事,北京药理学会理事,北京药学会理事。中国药理学会神经精神药理专业委员会、分子与生化药理学专业委员会委员、中国神经科学学会离子通道与受体分会委员、中国抗癫痫学会药物治疗专业委员会委员。

 

【简历】

1998—2002年  北京大学药学院,药学学士学位;

2003—2008年  英国University College London,神经药理学博士学位;

2008—2013年  英国University College London,博士后,神经药理学专业;

2013年至今     北京大学药学院    研究员      

 

【研究领域关键词】

离子通道、难治性癫痫病、抑郁症、候选药物发现和临床前研究

 

【研究兴趣】

 

1. 神经元微小结构中离子通道与神经精神系统疾病;

 

2. 难治性癫痫的离子通道机制研究;

 

3. 离子通道为靶标药物筛选与临床前研究;

 

【通讯方式】

北京市海淀区学院路38号北京大学医学部药学楼131室,邮编100191

电话:82805925(办公室);82805924(实验室)

Emailhuangz@hsc.pku.edu.cn

 

【代表性论文】

2024

 

1. Lai SR, Zhang LB, Tu XY, Ma XY, Song YJ, Cao KX, Shi YQ, Yang C, Li MM, Meng JH, Wu Q, Shi J*, Ma WN*, Li SY*, Xue YX* and Huang Z* (2024) Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams. Science Advances, 10(12):eadk9484.


2. Wang Y, Yang H, Li N, Wang L, Guo C, Ma W, Liu S, Peng C, Chen J, Song H, Chen H, Ma X, Yi J, Lian J, Kong W, Dong J, Tu X, Shah M, Tian X*, Huang Z* (2024) A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels. Adv Sci. (Weinh). e2400560.


3. Di C, Wu T, Gao K, Li N, Song HF, Sun HJ, Yi JY, Zhang XR, Chen JX, Shah MM*, Jiang YW*, Huang Z* (2024) Carvedilol inhibits neuronal hyperexcitability caused by epilepsy-associated KCNT1 mutations. British Journal of Pharmacology, Accepted


4. Chi P, Wang X, Li J, Yang H, Li K, Zhang Y, Lin S, Yu L, Liu S, Chen L, Ren R, Wu J, Huang Z*, Geng J*, Deng D* (2024) Molecular insights into the inhibition of proton-activated chloride channel by transfer RNA. Cell Res. 2024 Jun 28.


5. Yang H, Jing M, Tian C, Li B, Liao W, Wang W, Li Y, Wang X, Duan G, Sun Q*, Huang Z*, Wu L*. (2024) 1,4-Disubstituted Piperazin-2-Ones as Selective Late Sodium Current Inhibitors with QT Interval Shortening Properties in Isolated Rabbit Hearts. J Med Chem. Aug 8; 67(15):12676-12694.


6. Kong W, Zhu J, Shan PP, Ying HY, Chen TY, Zhang BW, Peng C, Wang ZH, Wang YF, Huang LT, Bi SZ, Ma WN*, Huang Z*, Zhu SJ*, Liu XY*, Li C* (2024) iSKIN: integrated application of machine learning and Mondrian conformal prediction to detect skin sensitizers in cosmetic raw materials. SmartMat. e1278.


7. Wei Y, Yu Z, Wang L, Li X, Li N, Bai Q, Wang Y, Li R, Meng Y, Xu H, Wang X, Dong Y, Huang Z*, Zhang XC, Zhao Y. (2024) Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors. Nat Commun. 15(1):2772.


8. Fan J, Guo C, Liao D, Ke H, Lei J, Xie W, Tang Y, Tominaga M, Huang Z*, Lei X* (2024) Structural Pharmacology of TRPV4 Antagonists. Adv Sci. (Weinh). e2401583.


9. Chen H, Xia Z, Dong J, Huang B, Zhang J, Zhou F, Yan R, Shi Y, Gong J, Jiang J, Huang Z*, Jiang D. (2024) Structural mechanism of voltage-gated sodium channel slow inactivation. Nat Commun. 15(1):3691.


10. Wang ZH, Zheng HR, Yang Hui, Song HF, Lian JJ, Peng C, Wang H, Zhang HB, Zheng YL, Wang QF, Ma L, Peng XD, Lan L, Huang Z* (2024) Cannabichromene from full-spectrum hemp extract exerts acute anti-seizure effects through allosteric activation of GABAA receptors, Fundamental research, Accepted


11. Kong WK, Lian JJ, Peng C, Zhu J, Zheng YL, Huang WR, Zhang BW, Duan GF, Ma L, Peng XD, Ma WN, Zhu SJ, Huang Z* (2024) Multistep-wise virtual screening identifies novel GABAA receptor positive allosteric modulators with new scaffolds, Acta Physico-Chimica Sinica, 40 (1) 2302044.
 

 

2023

1. Zhang J, Liu S, Fan J, Yan R, Huang B, Zhou F, Yuan T, Gong J, Huang Z*, Jiang D.* (2023) Structural basis of human Slo2.2 channel gating and modulation. Cell Rep. 42(8):112858.


2. Guo LK, Su Y, Zhang YY, Yu H, Lu Z, Li WQ, Yang YF, Xiao X, Yan H, Lu TL, Li J, Liao YD, Kang ZW, Wang LF, Li Y, Li M, Liu B, Huang HL, Lv LX, Yao Y, Tan YL, Breen G, Everall I, Wang HX, Huang Z*, Zhang D*, Yue WH*. (2023) Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis. Mil Med Res. 10(1):24.


3. 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


4. 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(1):516.


5. 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). 68(4):383-387


6. 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. 14(1):1030


7. Kong WK, Huang WR, Peng C, Zhang BW, Duan GF, Ma WN*, Huang Z* (2023) Multiple machine learning methods aided virtual screening of NaV1.5 inhibitors. Journal of Cellular and Molecular Medicine. 27(2):266-276.

 

2022

1. He L, Yu Z, Geng Z, Huang Z*, Zhang C, Dong Y, Gao Y, Wang Y, Chen Q, Sun L, Ma X, Huang B, Wang X, Zhao Y. (2022) Structure, gating and pharmacology of human CaV3.3 channel. Nature Communications. 13(1):2084


2. 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. 13(1):2713.


3. 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. 13(1):3329.


4. Fan MH, Liu YQ, Shang YF, Xue YX, Liang J, Huang Z* (2022) JADE2 is essential for hippocampal synaptic plasticity and cognitive, Biological Psychiatry. 92(10):800-814. 


5. Zhang JT#, Shi YQ#, Huang Z#, Li Y, Yang B, Gong JK, Jiang D* (2022) Structural basis for NaV1.7 inhibition by pore blockers, Nature Structural & Molecular Biology. 29(12):1208-1216.


6. Ma Z, Eaton M, Liu Y, Zhang J, Chen X, Tu X, Shi Y, Que Z, Wettschurack K, Zhang Z, Shi R, Chen Y, Kimbrough A, Lanman NA, Schust L, Huang Z*, Yang Y*. (2022) Deficiency of autism-related Scn2a gene in mice disrupts sleep patterns and circadian rhythms. Neurobiol Dis. 168:105690. 


7. Wang H#, Wu T#, Huang Z#, Huang J, Geng Z, Cui B, Yan Y, Zhang Y, Wang Y. Channel HCN4 mutation R666Q associated with sporadic arrhythmia decreases channel electrophysiological function and increases protein degradation. (2022) J Biol Chem. 13:102599.

 

2021

1. 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. 37(5):109931.


2. 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. 64(9):5551-5576.


3. 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.


4. 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.
 

2020

1. 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.


2. Gao M, Kong W, Huang Z* & Xie Z* (2020) Identification of Key Genes Related to Lung Squamous Cell Carcinoma Using Bioinformatics Analysis. International Journal of Molecular Sciences, 21(8), 2994.


3. Kong W, Gao M, Jin Y, Huang W, Huang Z* & Xie Z* (2020) Prognostic model of patients with liver cancer based on tumor stem cell content and immune process. Aging, 12(16):16555-16578


4. 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

 

2019

1. Jin XQ, Chen Q, Song Y, Zheng J, Xiao K, Shao S, Fu ZB, Yi M, Yang Y, and Huang Z* (2019) Dopamine D2 Receptors Regulate the Action Potential Threshold by Modulating T-type Calcium Channels in Stellate Cells of the Entorhinal Cortex, Journal of Physiology, 597(13):3363-3387. 


2. 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


3. 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. 182:111656

  

Before 2018

1. Xiao K, Sun Z, Jin X, Ma W, Song Y, Lai S, Chen Q, Fan M, Zhang J, Yue W, Huang Z* (2018) ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice. J Physiol. 596(19):4729-4752.


2. Zhang J, Chen X, K?rb? M, Zhao Y, An L, Wang R, Wang K, Huang Z* (2018) Anticonvulsant effect of dipropofol by enhancing native GABA currents in cortical neurons in mice. J Neurophysiol. 120(3):1404-1414.


3. 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.


4. Huang Z, Li G, Aguado C, Lujan R, Shah MM. (2017) HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals. Sci Rep. 10;7:40257


5. Huang Z* and Gibb A.J.* (2014) Mg2+ block properties of NMDA receptors in neonatal rat substantia nigra pars compacta dopaminergic neurones. Journal of Physiology, 592(10): 2059-78.


6. Huang Z, Lujan R, Kadurin I, Uebele VN, Renger JJ, Dolphin AC, Shah MM (2011) Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses. Nat Neurosci. 14(4):478-86.


7. Huang Z, Lujan R, Martinez-Hernandez J, Lewis AS, Chetkovich DM, Shah MM. (2012) TRIP8b-independent trafficking and plasticity of adult cortical presynaptic HCN1channels. J Neurosci. 32(42):14835-48


8. Huang Z, Walker MC, Shah MM (2009) Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis. J Neurosci. 29(35):10979-88.


9. Huang Z, Wang Q, Wang JY (2003) RP-HPLC Method for Determination of Propofol in Human Serum, The Chinese Journal of Clinical Pharmacology, 19: 293-296