北京大学药学院分子与细胞药理学系

【个人介绍】

黄卓，博士，特聘研究员，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药理系副主任、党支部书记。兼任中国药理学会理事，北京药理学会理事。中国药理学会神经精神药理专业委员会和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年毕业于北京大学药学院，获学士学位；

2003—2008 年毕业于英国University College London，获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主要从事离子通道药物筛选与确证、神经精神系统疾病新靶标发现、抗癫痫药物药理学的科研和教学工作。

【研究领域关键词】

脑疾病的离子通道机制、癫痫病、抑郁症、树突离子通道、轴突离子通道、药物筛选、脑片电生理、蛙卵电生理、高通量离子通道药物筛选

【研究兴趣】

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。本研究组主要应用离体脑切片和整体动物模型，通过采用细胞体电生理记录（somatic patch-clamping）、树突电生理记录（dendritic patch-clamping）、双光子显微钙离子荧光成像（two-photon calcium imaging）及谷胱氨酸释放（glutamate uncaging）等技术以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。

【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）

Email：huangz@hsc.pku.edu.cn

【课题组研究方向】

1. 神经元微小结构中离子通道的表达、分布、调控及其功能；

2. 离子通道为靶标的药物筛选与临床前研究；

3. 神经精神系统疾病新靶标发现与确证；

【代表性论文】

2023

1. 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
2. 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.
3. 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.

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. 2022 Apr 19;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. 2022 May 17; 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. Jun 9;13(1):3329. doi: 10.1038/s41467-022-31031-x.
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. 2022 Nov 15;92(10):800-814. doi: 10.1016/j.biopsych.2022.05.021.
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. 2022 Jun 15; 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. 2022 Oct 13:102599. doi: 10.1016/j.jbc.2022.102599. Epub ahead of print.
8. Kong WK, Huang WR, Peng C, Zhang BW, Duan GF, Ma WN*, Huang Z* (2022) Multiple machine learning methods aided virtual screening of NaV1.5 inhibitors. Journal of Cellular and Molecular Medicine. 27(2):266-276.

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. Nov 2;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. 13;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, 27;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., 15;182:111656

2018

1. 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 Neurophysiology, 120 (3):1404-1414
2. 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. Journal of Physiology, 596(19):4729-4752.

Before 2017

1. 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.
2. Huang Z, Li G, Aguado C, Lujan R, Shah MM. (2016) HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals. Scientific Reports 7:40257.
3. 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.
4. 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
5. 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.
6. Huang Z, Walker MC, Shah MM. (2009) Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis, Journal of Neuroscience, 29(35):10979-88.
7. 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
8. Sun ZM and Huang Z* (2015) Progress in Research of Hyperpolarization-activated Cation Non-selective Channels and Antiepileptic Drugs Targeting the Channels. Progress in Pharmaceutical Science, 39(2): 98-104. (Invited review)

【参与研究】

2022

1. Zhang X, Kong W, Gao M, Huang W, Peng C, Huang Z, Xie Z, Guo H. Robust prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer. J Cell Mol Med. 2022 Jul;26(13):3659-3674. doi: 10.1111/jcmm.17360. Epub 2022 Jun 23. PMID: 35735060; PMCID: PMC9258710.

2021

1. Zhang J, Chen X, Eaton M, Wu J, Ma Z, Lai S, Park A, Ahmad TS, Que Z, Lee JH, Xiao T, Li Y, Wang Y, Olivero-Acosta MI, Schaber JA, Jayant K, Yuan C, Huang Z, Lanman NA, Skarnes WC, Yang Y. * Severe deficiency of the voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice. Cell Rep. 2021 Aug 3;36(5):109495. doi: 10.1016/j.celrep.2021.109495. PMID: 34348148;
2. Que Z, Olivero-Acosta MI, Zhang J, Eaton M, Tukker AM, Chen X, Wu J, Xie J, Xiao T, Wettschurack K, Yunis L, Shafer JM, Schaber JA, Rochet JC, Bowman AB, Yuan C, Huang Z, Hu CD, Trader DJ, Skarnes WC, Yang Y. * (2021) Hyperexcitability and pharmacological responsiveness of cortical neurons derived from human iPSCs carrying epilepsy-associated sodium channel Nav1.2-L1342P genetic variant. J Neurosci. 41(49):10194-10208.
3. Zhu J, Wang J, Wang X, Gao M, Guo B, Gao M, Liu J, Yu Y, Wang L, Kong W, An Y, Liu Z, Sun X, Huang Z, Zhou H*, Zhang N*, Zheng R*, Xie Z.* (2021) Prediction of drug efficacy from transcriptional profiles with deep learning. Nat Biotechnol. 39(11):1444-1452.
4. Ma H, Li CY, Wang JP, Zhang XC, Li MY, Zhang R, Huang Z, Zhang Y* (2021) Amygdala-hippocampal innervation modulates stress-induced depressive-like behaviors through AMPA receptors, PNAS, 118(6):e2019409118.

2020

1. Chen X, Zhang J, Song Y, Yang P, Yang Y, Huang Z & Wang K*. (2020) Deficiency of anti-inflammatory cytokine IL-4 leads to neural hyperexcitability and aggravates cerebral ischemia-reperfusion injury. Acta Pharm Sin B. 10(9):1634-1645.
2. Eaton M, Zhang J, Ma Z, Park AC, Lietzke E, Romero CM, Liu Y, Coleman ER, Chen X, Xiao T, Que Z, Lai S, Wu J, Lee JH, Palant S, Nguyen HP, Huang Z, Skarnes WC, Koss WA, Yang Y* (2020) Generation and basic characterization of a gene-trap knockout mouse model of Scn2a with a substantial reduction of voltage-gated sodium channel Nav1.2 expression, Genes, Brain and Behavior, 25:e12725.

Before 2019

1. Wang X, Su Y, Yan H, Huang Z, Huang Y, Yue W. (2019) Association Study of Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia. Front Psychiatry, 10:633.
2. Li W, Liu J, Fan M, Li Z, Chen Y, Zhang G, Huang Z, Zhang L*. (2018) Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder. Molecules. 24;23(5)
3. Li X, Liu D, Ma Y, Du X, Jing J, Wang L, Xie B, Sun D, Sun S, Jin X, Zhang X, Zhao T, Guan J, Yi Z, Lai W, Zheng P, Huang Z, Chang Y, Chai Z, Xu J, Deng H.（2017）Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State. Cell Stem Cell. S1934-5909(17) 30185-6.
4. Martinello K, Huang Z, Lujan R, Tran B, Watanabe M, Cooper EC, Brown DA, Shah MM. (2015) Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells, Neuron, 85: 346-363
5. Zhou J, Tang Y, Zheng Q, Li M, Yuan T, Chen L, Huang Z, Wang K. (2015) Different KChIPs compete for heteromultimeric assembly with pore-forming Kv4 subunits. Biophysical Journal, 108(11):2658-69.
6. Shah MM*, Huang Z, Martinello K. (2013) HCN and K(V)7 (M-) channels as targets for epilepsy treatment. Neuropharmacology, 69:75-81. (Invited review)
7. Ren LB, Wang XY, Xie Q, Liu JX, Huang Z, Du Ying, Wang JY (2007) Study on correlation of contents of light rare earth elements in rats’brains, Chinese Journal Of Analysis Laboratory, 26: 108-111
8. Ren LB, Wang XY, Xie Q, Liu JX, Huang Z, Du Ying, Wang JY (2007) Study on correlation of contents of light rare earth elements in rats’brains, Chinese Journal of Analysis Laboratory, 26: 108-111
9. Liu JX, Wang XY, Xie Q, Liu Y, Zhang JH, Huang Z, Ren LB, Du Y, Wang JY (2007) Study on the characteristics of content and distribution of light rare earth elements in rat testis, Journal of Hygiene Research, 06: 734-736
10. Wang JY, Ouyang L, Liu YQ, Xie Q, Huang Z, Tu P F, Guo XL, Liu HS (2004), Preliminary attempt at the speciation of 25-elements in the chinese medicinal herb, China Journal of Chinese Materia Medica, 29: 753-759
11. Wang JY, Zhu HD, Ouyang L, Liu YQ, Wang XY, Huang Z, Wang NF, Liu HS (2004), Determination of trace Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS, Specroscopy and Spectral Analysis, 24: 1117-1120

师资队伍

黄卓