研究员
张金伟
职  称: 研究员
学  历: 博士研究生
电  话: 021-54925377
职  务: 课题组长
传  真:
电子邮件: jinweizhang@sioc.ac.cn
个人网页:
通信地址: 上海市零陵路345号
个人简历

2023年12月-至今:研究员,课题组长,中国科学院上海有机所-生命过程小分子调控全国重点实验室

2017年7月-2023年12月:Principal Investigator,博士生导师,终身教职(高级职称),英国埃克塞特大学医学院(英格兰)

2016年7月-2017年6月:Research Investigator, 英国医学研究理事会(MRC)蛋白质磷酸化与泛素化研究所(PPU),英国邓迪大学(苏格兰)

2015年7月-2016年6月:Research Investigator, 耶鲁大学医学院,美国康涅狄格州纽黑文市

2011年7月-2015年6月:博士后研究员,英国医学研究理事会(MRC)蛋白质磷酸化与泛素化研究所(PPU),英国邓迪大学(苏格兰)

2008年3月-2011年5月:博士研究生,生物化学专业,英国纽卡斯尔大学(英格兰)

2004年9月-2007年7月:硕士研究生,海洋生物学专业,国家海洋局第三海洋研究所

1999年9月-2003年7月:本科学生,生物工程专业,福建师范大学生命科学学院


研究方向

主要研究方向

1. 研究主要集中在细胞信号转导和药物作用机制上。探究激酶、转录因子、离子通道、离子共转运蛋白等在信号传导中的作用,比如WNK-SPAKTLR4-NF-κB通路,也研究离子共转运蛋白(CCCsSLC12家族,包括SLC12A1(NKCC2)SLC12A2(NKCC1)SLC12A3(NCC)SLC12A5(KCC2)SLC12A6(KCC3)等成员)在维持细胞内外钠、钾、氯离子稳态与细胞膜电势变化在细胞正常生理和各种疾病状态(病理)中的功能。目前对多种激酶和转运蛋白等的细胞信号转导和药物作用机制的研究进一步拓展到肿瘤炎症、肿瘤微环境和免疫机制、细胞凋亡的调控,以及相关疾病的生物学特征。此外,进行小分子药物和天然微生物产物的活性分析与鉴定。这些研究旨在揭示疾病的发生和发展机制,为诊断和治疗提供科学依据,并推动新药研发。

其他研究方向

1. 利用下一代测序技术(如外显子测序)解析重要临床疾病的突变分子,并通过CRISPR-Cas9等技术构建相应的细胞和动物模型,以深入研究疾病生物学。

2. 在微生物研究领域,致力于海洋微生物新种的鉴定、工业微生物育种、及其酶的开发和发酵工程,以及筛选海洋放线菌来源的抗菌小分子活性分子。此外,研究化学难合成或化学合成成本高的长链不饱和脂肪酸,如EPA(二十碳五烯酸)和DHA(二十二碳六烯酸)的生物合成。

3. 在绿色能源领域,包括对电化学和微生物电池的研究开发。


社会任职
兼任Medicinal Research Reviews (Editorial Board)、Journal of Modern Biology and Drug Discovery (Editor in Chief)、 Frontiers in Pharmacology (Associate Editor)、 Frontiers in Microbiology (Associate Editor)、和 Frontiers in Physiology (Associate Editor)等10多个国际权威杂志的Editor或 Editorial Board Member;
受邀担任Chem、 Advanced Science、Pharmacology & Therapeutics、和Clinical and Translational Medicine等60多本国际权威杂志的审稿人;
受邀担任英国MRC Neurosciences and Mental Health Board Member、英联邦奖学金委员会(Commonwealth Scholarship Commission,CSC) Panel Adviser、和the MRC Impact Acceleration Account (IAA) Panel Member;
受邀为英国MRC、BBSRC、British Heart Foundation(BHF)、苏格兰Carnegie Trust、奥地利科学基金(FWF)、中国科学院国际合作局-澳门科技基金、和国家自然科学基金等的基金通讯评审专家。
获奖及荣誉

Fellow of the Higher Education Academy UK (FHEA, 英国高等教育学会会士);

Fellow of the Royal Society of Biology (FRSB, 英国皇家生物学会会士);

Member of Sigma Xi,The Scientific Research Honor Society (美国Sigma Xi科学研究荣誉学会会员);

2024年,Biochemical Society (英国生物化学学会) Travel Award 参加国际会议旅行奖;

2021年,国家相关人才计划;

2021年,英国埃克塞特大学“学术团队建设”方面获得优秀奖;

2019年,福建省“闽江学者奖励计划”;

2019年,英国埃克塞特大学“科研原创性方面处于世界领先的质量”方面获得超越奖;

2012年,英国帕金森病协会Travel Award 参加会议旅行奖;

2011年,英国医学研究理事会MRC-Career Development Award职业生涯发展奖;

2010年,美国油脂化学家协会(American Oil Chemists' Society, AOCS)优秀青年科学家奖;

2010年,美国油脂化学家协会(American Oil Chemists' Society, AOCS)优秀论文一等奖;

2008年,英国政府生物技术与生物科学研究理事会(BBSRC)”多萝西·霍奇金博士研究生奖(DHPA), 全额博士奖学金”(多萝西·霍奇金为英国首位女科学家在1964年获得诺贝尔化学奖);

2008年,国家海洋局极地研究优秀论文三等奖(两项研究成果);

2006年,中国酶制剂及生物催化产品技术开发与产业化会议,获得诺维信(Novozymes,中国)投资有限公司资助参加会议奖;

2005年,福建省海洋学会优秀论文二等奖;

2005年,中国酶工程学会优秀青年论文奖;

2002年,福建省大学生创业大赛三等奖(作为团队负责人);

2001年,大学生记念建党八十周年暨第五次邓小平理论研讨会优秀论文三等奖。

代表论著

(1) Li, L.; Huang, W.; Ren, X.; Wang, Z.; Ding, K.; Zhao, L.; Zhang, J.* Unlocking the potential: advancements and future horizons in ROR1-targeted cancer therapies. Sci China Life Sci 2024, 67(12), 2603–2616.

(2) McMoneagle, E.; Zhou, J.; Zhang, S.; Huang, W.; Josiah, S. S.; Ding, K.; Wang, Y.; Zhang, J.* Neuronal K(+)-Cl(-) cotransporter KCC2 as a promising drug target for epilepsy treatment. Acta Pharmacol Sin 2024, 45, 1–22.  

(3) Geng, W.; Thomas, H.; Chen, Z.; Yan, Z.; Zhang, P.; Zhang, M.; Huang, W.; Ren, X.; Wang, Z.; Ding, K.; Zhang, J.* Mechanisms of acquired resistance to HER2-Positive breast cancer therapies induced by HER3: A comprehensive review. Eur J Pharmacol 2024, 977, 176725.

(4) Trinder, A.; Ding, K.; Zhang, J.*The therapeutic significance of HER3 in non-small cell lung cancer (NSCLC): A review study. Curr Med Chem 2024, 31:CMC-EPUB-137360. 

(5) Zhang, J.* Microbial stars: shedding light on gut microbes' role in insulin resistance and innovative diabetes therapies. Gut Microbes 2024, 16 (1), 2307581.

(6) Zhang, J.* Hereditary causes of hypertension due to increased sodium transport. Curr Opin Pediatr 2024, 36 (2), 211-218.

(7) Zhang, J.*;Sabatier, J.-M.; Chahine, M.; Tricarico, D. Editorial: Reviews in pharmacology of ion channels and channelopathies. Front Pharmacol 2024, 15.

(8) Pracucci, E.; Graham, R. T.; Alberio, L.; Nardi, G.; Cozzolino, O.; Pillai, V.; Pasquini, G.; Saieva, L.; Walsh, D.; Landi, S.; Zhang, J.; et al. Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability. Nat Commun 2023, 14 (1), 7108.

(9) . Zhang, J.* Commentaries: Lecanemab: pioneering the way as the first approved drug for Alzheimer's disease treatment. Inflamm Res 2023, 72 (9), 1873-1876.

(10) Zhang, S.; Meor Azlan, N. F.; Josiah, S. S.; Zhou, J.; Zhou, X.; Jie, L.; Zhang, Y.; Dai, C.; Liang, D.; Li, P.; et al. Zhang, J.* The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies. J Pharm Anal 2023, 13 (12), 1471-1495.

(11) Zhang, J.*; Hartmann, A. M.; Guo, J. Editorial: Chloride homeostasis in animal cell physiology. Front Physiol 2023, 14, 1227565.

(12) Zhang, J.*; Wang, J.; Labes, A.; Zeng, R. Marine microbial-derived molecules and their potential medical and cosmetic applications, volume II. Front Microbiol 2023, 14, 1188008.

(13) Robert, S. M.; Reeves, B. C.; Kiziltug, E.; Duy, P. Q.; Karimy, J. K.; Mansuri, M. S.; Marlier, A.; Allington, G.; Greenberg, A. B. W.; DeSpenza, T., Jr.; Zhang, J.; et al. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell 2023, 186 (4), 764-785 e721.

(14) Zhang, J.*; Siew, K.; Sun, D. Targeting pumps, channels and transporters for the treatments of vascular, cardiovascular and kidney diseases. Front Pharmacol 2023, 14, 1130882.

(15) Josiah, S. S.; Meor Azlan, N. F.; Oguro-Ando, A.; Zhang, J.* Study of the functions and activities of neuronal K-Cl co-transporter KCC2 using western blotting. J Vis Exp 2022,  (190), e64179.

(16) Kury, S.*; Zhang, J.*; Besnard, T.; Caro-Llopis, A.; Zeng, X.; Robert, S. M.; Josiah, S. S.; Kiziltug, E.; Denomme-Pichon, A. S.; Cogne, B.; et al. Rare pathogenic variants in WNK3 cause X-linked intellectual disability. Genet Med 2022, 24 (9), 1941-1951.

(17) D’Silva, E.; Meor Azlan, N. F.; Zhang, J.*Angiotensin II Receptor Blockers in the Management of Hypertension in Preventing Cognitive Impairment and Dementia—A Systematic Review. Pharmaceutics 2022, 14 (10).

(18) Zhang, J.*; Yao, J.; Rong, M. Role of Ion Channels in Pain. Front Pharmacol 2022, 13, 884665.

(19) Zhong, C.; Zhao, H.; Xie, X.; Qi, Z.; Li, Y.; Jia, L.*; Zhang, J.*; Lu, Y.* Protein Kinase C-Mediated Hyperphosphorylation and Lateralization of Connexin 43 Are Involved in Autoimmune Myocarditis-Induced Prolongation of QRS Complex. Front Physiol 2022, 13.

(20) Salihu, S.; Meor Azlan, N.; Josiah, S.; Wu, Z.; Wang, Y.; Zhang, J.* Role of the cation-chloride-cotransporters in the circadian system. Asian J Pharm Sci 2020, 16 (5), 589-597.

(21) Chen, Z.; Zhang, J.; Murillo-de-Ozores, A. R.; Castaneda-Bueno, M.; D'Amico, F.; Heilig, R.; Manning, C. E.; Sorrell, F. J.; D'Angiolella, V.; Fischer, R.; et al. Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase. Biochem J 2022, 479 (5), 661-675.

(22) Zhang, J.*; Zeng, R.; Labes, A. Marine Microbial-Derived Molecules and Their Potential Medical and Cosmetic Applications. Front Microbiol 2021, 12.

(23) Bertoni, A.; Schaller, F.; Tyzio, R.; Gaillard, S.; Santini, F.; Xolin, M.; Diabira, D.; Vaidyanathan, R.; Matarazzo, V.; Medina, I.; Zhang, J.; et al. Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism. Mol Psychiatry 2021, 26 (12), 7582-7595.

(24) Meor Azlan, N. F.; Koeners, M. P.; Zhang, J.* Regulatory control of the Na+-Cl- co-transporter NCC and its therapeutic potential for hypertension. Acta Pharm Sin B 2021, 11 (5), 1117-1128.

(25) Brown, A.; Meor Azlan, N. F.; Wu, Z.; Zhang, J.* WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension. Acta Pharmacol Sin 2021, 42 (4), 508-517.

(26) Josiah, S. S.; Meor Azlan, N. F.; Zhang, J.* Targeting the WNK-SPAK/OSR1 pathway and cation-chloride cotransporters for the therapy of stroke. Int J Mol Sci 2021, 22 (3), 1232.

(27) Meor Azlan, N. F.; Zhang, J.* Role of the cation-chloride-cotransporters in cardiovascular disease. Cells 2020, 9 (10), 2293.

(28) Andrews, K.; Josiah, S. S.; Zhang, J.* The therapeutic potential of neuronal K+-Cl- co-transporter KCC2 in Huntington's disease and its comorbidities. Int J Mol Sci 2020, 21 (23), 9142.

(29) Zhang, J.; Cordshagen, A.; Medina, I.; Nothwang, H. G.; Wisniewski, J. R.; Winklhofer, M.; Hartmann, A. M. Staurosporine and NEM mainly impair WNK-SPAK/OSR1 mediated phosphorylation of KCC2 and NKCC1. PLoS One 2020, 15 (5), e0232967.

(30) Zhang, J.*; Bhuiyan, M. I. H.; Zhang, T.; Karimy, J. K.; Wu, Z.; Fiesler, V. M.; Zhang, J.; Huang, H.; Hasan, M. N.; Skrzypiec, A. E.; et al. Modulation of brain cation-Cl(-) cotransport via the SPAK kinase inhibitor ZT-1a. Nat Commun 2020, 11 (1), 78.

(31) Watanabe, M.#; Zhang, J.#; Mansuri, M. S.; Duan, J.; Karimy, J. K.; Delpire, E.; Alper, S. L.; Lifton, R. P.; Fukuda, A.; Kahle, K. T. Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. Sci Signal 2019, 12 (603), eaaw9315.

(32) Pisella, L. I.; Gaiarsa, J. L.; Diabira, D.; Zhang, J.; Khalilov, I.; Duan, J.; Kahle, K. T.; Medina, I. Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology. Sci Signal 2019, 12 (603), eaay0300.

(33) Duran, D.; Zeng, X.; Jin, S. C.; Choi, J.; Nelson-Williams, C.; Yatsula, B.; Gaillard, J.; Furey, C. G.; Lu, Q.; Timberlake, A. T.; Zhang, J.; et al. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron 2019, 101 (3), 429-443.e424.

(34) Dumon, C.; Diabira, D.; Chudotvorova, I.; Bader, F.; Sahin, S.; Zhang, J.; Porcher, C.; Wayman, G.; Medina, I.; Gaiarsa, J. L. The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice. Elife 2018, 7.

(35) Zhang, J.*; Karimy, J. K.; Delpire, E.; Kahle, K. T*. Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport. Expert Opin Ther Targets 2017, 21 (8), 795-804.

(36) Karimy, J. K. #; Zhang, J. #; Kurland, D. B.; Theriault, B. C.; Duran, D.; Stokum, J. A.; Furey, C. G.; Zhou, X.; Mansuri, M. S.; Montejo, J.; et al. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med 2017, 23 (8), 997-1003.

(37) Heubl, M.; Zhang, J.; Pressey, J. C.; Al Awabdh, S.; Renner, M.; Gomez-Castro, F.; Moutkine, I.; Eugene, E.; Russeau, M.; Kahle, K. T.; et al. GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl(-)-sensitive WNK1 kinase. Nat Commun 2017, 8 (1), 1776.

(38) Zhang, J.; Burgess, J. G. Enhanced eicosapentaenoic acid production by a new deep-sea marine bacterium Shewanella electrodiphila MAR441T. PLoS One 2017, 12 (11), e0188081.

(39) Shekarabi, M.; Zhang, J.; Khanna, A. R.; Ellison, D. H.; Delpire, E.; Kahle, K. T. WNK Kinase Signaling in Ion Homeostasis and Human Disease. Cell Metab 2017, 25 (2), 285-299.

(40) Kahle, K. T.; Schmouth, J. F.; Lavastre, V.; Latremoliere, A.; Zhang, J.; Andrews, N.; Omura, T.; Laganiere, J.; Rochefort, D.; Hince, P.; et al. Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. Sci Signal 2016, 9 (421), ra32.

(41) Zhang, J.*; Gao, G.; Begum, G.; Wang, J.; Khanna, A. R.; Shmukler, B. E.; Daubner, G. M.; de Los Heros, P.; Davies, P.; Varghese, J.; et al. Functional kinomics establishes a critical node of volume-sensitive cation-Cl(-) cotransporter regulation in the mammalian brain. Sci Rep 2016, 6, 35986.

(42) Zhang, J.; Deng, X.; Kahle, K. T. Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition. Sci Signal 2016, 9 (450), e3.

(43) Kahle, K. T.; Flores, B.; Bharucha-Goebel, D.; Zhang, J.; Donkervoort, S.; Hegde, M.; Hussain, G.; Duran, D.; Liang, B.; Sun, D.; et al. Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter. Sci Signal 2016, 9 (439), ra77.

(44) Zhang, J.*; Siew, K.; Macartney, T.; O'Shaughnessy, K. M.; Alessi, D. R. Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet 2015, 24 (16), 4545-4558.

(45) Kazlauskaite, A.; Martínez-Torres, R. J.; Wilkie, S.; Kumar, A.; Peltier, J.; Gonzalez, A.; Johnson, C.; Zhang, J.; Hope, A. G.; Peggie, M.; et al. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. EMBO Rep 2015, 16 (8), 939-954.

(46) Hatcher, J. M.; Zhang, J.; Choi, H. G.; Ito, G.; Alessi, D. R.; Gray, N. S. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett 2015, 6 (5), 584-589.

(47) Friedel, P.#; Kahle, K. T.#; Zhang, J.#; Hertz, N.; Pisella, L. I.; Buhler, E.; Schaller, F.; Duan, J.; Khanna, A. R.; Bishop, P. N.; et al. WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Sci Signal 2015, 8 (383), ra65.

(48) Schumacher, F. R.#; Siew, K.#; Zhang, J.; Johnson, C.; Wood, N.; Cleary, S. E.; Al Maskari, R. S.; Ferryman, J. T.; Hardege, I.; Yasmin; et al. Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia. EMBO Mol Med 2015, 7 (10), 1285-1306. DOI: 10.15252/emmm.201505444.

(49) Zhang, J.; Burgess, J. G. Shewanella electrodiphila sp. nov., a psychrotolerant bacterium isolated from Mid-Atlantic Ridge deep-sea sediments. Int J Syst Evol Microbiol 2015, 65 (9), 2882-2889.

(50) de Los Heros, P.; Alessi, D. R.; Gourlay, R.; Campbell, D. G.; Deak, M.; Macartney, T. J.; Kahle, K. T.; Zhang, J.* The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J 2014, 458 (3), 559-573.

(51) Alessi, D. R.; Zhang, J.; Khanna, A.; Hochdorfer, T.; Shang, Y.; Kahle, K. T. The WNK-SPAK/OSR1 pathway: Master regulator of cation-chloride cotransporters. Sci Signal 2014, 7 (334), re3.

(52) Choi, H. G.#; Zhang, J.#; Deng, X.#; Hatcher, J. M.; Patricelli, M. P.; Zhao, Z.; Alessi, D. R.; Gray, N. S. Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett 2012, 3 (8), 658-662.

(53) Zhang, J.; Deng, X.; Choi, HG.; Alessi, DR.; Gray, NS. Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorg Med Chem Lett 2012, 22 (5), 1864-1869.

(54) Zhang, J.; Zhang, E.; Scott, K.; Burgess, J. G. Enhanced electricity production by use of reconstituted artificial consortia of estuarine bacteria grown as biofilms. Environ Sci Technol 2012, 46 (5), 2984-2992.

(55) Zhang, J.*; Zeng, R. Molecular cloning and expression of an extracellular α-amylase gene from an Antarctic deep sea psychrotolerant Pseudomonas stutzeri strain 7193. World J Microbiol Biotechnol 2011, 27 (4), 841-850.

(56) Zhang, J.; Zeng, R. Purification and characterization of a cold-adapted alpha-amylase produced by Nocardiopsis sp. 7326 isolated from Prydz Bay, Antarctic. Mar Biotechnol (New York, N.Y.) 2008, 10 (1), 75-82.

(57) Zhang, J.; Zeng, R. Molecular cloning and expression of a cold-adapted lipase gene from an Antarctic deep sea psychrotrophic bacterium Pseudomonas sp. 7323. Mar Biotechnol (New York, N.Y.) 2008, 10 (5), 612-621.

(58) Zhang, J.; Zeng, R. Psychrotrophic amylolytic bacteria from deep-sea sediment of Prydz Bay, Antarctic: diversity and characterization of amylases. World J Microbiol Biotechnol 2007, 23 (11), 1551-1557

(59) Zhang, J.; Lin, S.; Zeng, R. Cloning, expression, and characterization of a cold-adapted lipase gene from an antarctic deep-sea psychrotrophic bacterium, Psychrobacter sp 7195. J Microbiol Biotechnol 2007, 17 (4), 604-610.  From NLM.

(60) Zhang, J.*; Zeng, R.* Cloning, expression and characterization of the cold Active lipase (Lip3) from metagenomic DNA of an Antarctic deep-sea sediment. Prog Biochem Biophys 2006, 33 (12), 1207-1214.

承担科研项目情况

中国科学院相关人才计划项目(2024-2026)

国家相关人才计划项目(2024-2026)

国家自然科学基金面上项目(2022-2025)

国家自然科学基金-英国皇家学会国际交流项目 (2021-2022)

国家自然科学基金面上项目(2020-2023)