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研究员

于海波

职 称:研究员

所属科室:药理学研究室

导师类别:博士生导师

联系方式:haiboyu@www.myhortonhome.com

所属重点实验室:天然药物活性物质与功能国家重点实验室
新药作用机制研究与药效评价北京市重点实验室

个人简介

2005年毕业于北京协和医学院bobapp官方中国有限公司 ,获药理学专业理学博士学位; 2008年至2013年在美国约翰霍普金斯大学医学院神经科学系、离子通道中心进行博士后研究。2014年3月以引进人才方式加入bobapp官方下载 。 主要围绕疾病相关的离子通道,建立离子通道药物研发平台,发现新颖离子通道药物以及开展小分子调控机制研究。先后主持国家自然科学基金3项,科技部重大新药创制-科技重大专项1项,此外还获得天然药物活性物质与功能国家重点实验室自主课题、教育部留学回国人才启动金以及bobapp官方下载 “引进人才”启动基金的资助。在PNAS等国际学术期刊共发表文章近20余篇。

研究方向

离子通道是一类重要的跨膜蛋白,参与许多重要的生理过程。离子通道功能异常,与疾病的发生息息相关。本课题组围绕疾病相关的离子通道,围绕癫痫、疼痛以及焦虑抑郁等疾病相关靶点,建立了较完备的离子通道筛选平台资源体系,在研究中不断丰富离子通道靶点细胞株的亚型种类和相应的功能筛选评价体系,开展药物筛选和创新药物研究。 本课题组围绕与神经系统疾病相关的离子通道,主要开展以下工作:
1. 以离子通道为靶点的新颖调节剂的发现;
2. 开发靶向癫痫、疼痛以及焦虑抑郁等神经系统疾病的创新药物;
3. 探索和挖掘小分子化合物的新颖作用机制,为疾病治疗寻找新的思路。

发表论文

1. Keliang Chen# , Tao Wang# , Yong Li# , Jun Wu# , Cheng-Xiao Zhao , Sheng Liu , Fengrun Sun , Yehong Fang , Jiahuan Hu , Jinping Hu , Chong-Jing Zhang* , Haibo Yu* , Chao Ma* , Shi-Shan Yu*. Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain. Acta Pharm Sin B. 2023 Mar;13(3):1326-1336.
2. Shaohua Li , Yuchen Jin , Min Li , Haibo Yu*.NAN-190, a 5-HT1A antagonist, alleviates inflammatory pain by targeting Nav1.7 sodium channels. Life Sci . 2023 Apr 15;319:121520.
3. Jianan Song# , Mengyuan Jiang# , Yuchen Jin# , Hongrui Li , Yanhong Li , Yumei Liu , Haibo Yu* , Xiangzhong Huang*. Phytol from Faeces Bombycis alleviated migraine pain by inhibiting Nav1.7 sodium channels. J Ethnopharmacol. 2023 Apr 24;306:116161. doi: 10.1016/j.jep.2023.116161. Epub 2023 Jan 14. PMID: 36646158
4. Qingfei Meng , Xue Ren , Rui Wang , Yu Han , Xiufen Li , Qin Zhang , Zhenpeng Li , Yuexing Wang , Longjiang Huang *, Haibo Yu*.Design, synthesis, anticonvulsant activity and structure-activity relationships of novel 7-Azaindole derivatives. Bioorganic Chemistry . 2023 Apr;133:106430.
5. Jun Wu#, Zhipeng Hou#, Yan Wang, Liping Chen, Chengxi Lian, Qingfei Meng, Chaoying Zhang, Xiufen Li, Longjiang Huang*, Haibo Yu*,Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity, Bioorganic Chemistry, Volume 119, 2022, 105565, ISSN 0045-2068.
6. Min Li, Haibo Yu *. Identification of WP1066, an inhibitor of JAK2 and STAT3, as a Kv1.3 potassium channel blocker. Bri J Pharmacol . 2021, 178(13):2617-2631.
7. Ning Sheng, Hao Zheng, Min Li, Menglin Li, Zhe Wang, Ying Peng, Haibo Yu*, Jinlan Zhang*. 4,5 caffeoylquinic acid and scutellarin, identified by integrated metabolomics and proteomics approach as the active ingredients of Dengzhan Shengmai, act against chronic cerebral hypoperfusion by regulating glutamatergic and GABAergic synapses. Pharmacological Research 152 (2020) 104636.
8. Longjiang Huang*,Jing Ding, Min Li, Zhipeng Hou, Yanru Geng, Xiufen Li and Haibo Yu*.Discovery of [1,2,4]-triazolo [1,5-a]pyrimidine-7(4H)-one derivatives as positive modulators of GABAA1 receptor with potent anticonvulsant activity and low toxicity. Europe Journal of Medicinal Chemistry. 2020 Jan 1;185:111824.
9. Jiamin Feng, Min Li, Jinlian Zhao, Xiaona Jia, Jimei Liu, Min Zhang, Ridao Chen, Kebo Xie , Dawei Chen, Haibo Yu*, Jungui Dai*. Three new phenylspirodrimane derivatives with inhibitory effect towards potassium channel Kv1.3 from the fungus Stachybotrys chartarum. J Asian Nat Prod Res. 2019 Sep;21(9):887-894.
10. Min Li#, Ying Wu#, Beiyan Zou, Xiaoliang Wang, Min Li and Haibo Yu*. Identification of WB4101, an alpha1-adrenoceptor antagonist, as a sodium channel blocker. Mol Pharmacol. 2018, 94(2):896-906. (#,co-first authors)
11. Ying Wu#., Beiyan Zou#., Lingli Liang, Min Li, Yuanxiang Tao, Haibo Yu*., Xiaoliang Wang*., Min Li*, Loperamide inhibits sodium channels to alleviate inflammatory hyperalgesia, Neuropharmacology. 2017, 117: 282-291. (#,co-first authors)
12. Haibo Yu*, Min Li, Weiping Wang, Xiaoliang Wang*. High throughput screening technologies for ion channels. Acta Pharmacol Sin. 2016,37(1):34-43.
13. Haibo Yu*, Beiyan Zou*, Xiaoliang Wang, Min Li. Investigation of miscellaneous hERG inhibition in large diverse compound collection using automated patch-clamp assay. Acta Pharmacol Sin. 2016,37(1):111-23.
14. Haibo Yu*., Beiyan Zou, Xiaoliang Wang, Min Li. Effect of Tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels. Brit J Pharmacol. 2015, 172(13):3370-82
15. Christian J Peters, Haibo Yu, Jason Tien, Yuh Nung Jan, Min Li, Lily Yeh Jan*. Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels. Proc Natl Acad Sci U S A. 2015 112(11):3547-52.
16. Haibo Yu, Zhihong Lin, Margrith E Mattmann, Beiyan Zou, Cecile Terrenoire, Hongkang Zhang, Meng Wu, Owen B McManus, Robert S Kass, Craig W Lindsley, Corey R Hopkins*, Min Li*. Dynamic Subunit Stoichiometry Confers a Progressive Continuum of Pharmacological Sensitivity by KCNQ Channels. Proc Natl Acad Sci U S A 110, 2013,8732-8737.
17. Pingzheng Zhou, Haibo Yu, Min Gu, Fa-jun Nan, Zhaobing Gao, Min Li. PIP2 alters pharmacological selectivity for epilepsy-causing KCNQ channels. Proc Natl Acad Sci U S A 110, 8726-8731, 2013.
18. Hongkang Zhang#, Beiyan Zou#, Haibo Yu#, Alessandra Moretti, Xiaoying Wang, Wei Yan, Joseph J Babcock, Milena Bellin, Owen B McManus, Gordon Tomaselli, Fajun Nan, Karl-Ludwig Laugwitz, Min Li*. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel. Proc Natl Acad Sci U S A 2012,109, 11866-11871.
19. Haibo Yu, Meng Wu, Steven D Townsend, Beiyan Zou, Shunyou Long, J Scott Daniels, Owen B McManus, Min Li*, Craig W Lindsley, Corey R Hopkins*. Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS chem neurosci 2011, 2, 572-577.
20. Yiu-Yin Cheung, Haibo Yu, Kaiping Xu, Beiyan Zou, Meng Wu, Owen B McManus, Min Li*, Craig W Lindsley, Corey R Hopkins*. Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor. J Med Chem 2012, 55, 6975-6979.
21. Margrith E Mattmann , Haibo Yu, Zhihong Lin, Kaiping Xu, Xiaofang Huang, Shunyou Long, Meng Wu, Owen B McManus, Darren W Engers, Uyen M Le, Min Li*, Craig W Lindsley, Corey R Hopkins*. Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1 -tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K(v)7.1 (KCNQ1) potassium channel activator. Bioorg Med Chem Lett 2012, 22, 5936-5941.
22. Fang Du, Haibo Yu, Beiyan Zou, Joseph Babcock, Shunyou Long, Min Li*. hERGCentral: a large database to store, retrieve, and analyze compound-human Ether-a-go-go related gene channel interactions to facilitate cardiotoxicity assessment in drug development. Assay Drug Dev Technol 2011, 9, 580-588.
23. Hao-Ran Wang, Meng Wu, Haibo Yu, Shunyou Long, Amy Stevens, Darren W Engers, Henry Sackin, J Scott Daniels, Eric S Dawson, Corey R Hopkins, Craig W Lindsley, Min Li, Owen B McManus. Selective inhibition of the K(ir)2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR, and pharmacological characterization of ML133. ACS Chem Biol 2011, 6, 845-856.
24. Beiyan Zou, Haibo Yu, Joseph J Babcock, Pritam Chanda, Joel S Bader, Owen B McManus, Min Li*. Profiling diverse compounds by flux- and electrophysiology-based primary screens for inhibition of human Ether-a-go-go related gene potassium channels. Assay Drug Dev Technol 2010, 8, 743-754.
25. 宋佳男,刘玉梅*,于海波*。神经病理性疼痛的治疗和药物发现现状。药学学报 (Acta Pharmaceutica Sinica) 2021, 56(3): 679 −688。
26. 刘颖,孔令飞*,于海波*。癫痫的治疗和药物发现现状。药学学报 (Acta Pharmaceutica Sinica) 2021, 56(4): 924 −938。
27. 吴军,于海波*。大麻二酚在神经精神疾病中的作用与分子机制研究进展。药学学报 (Acta Pharmaceutica Sinica) 2020, 55(12): 2800-2810。
28. 周宇,王晓良,于海波*。离子通道作为糖尿病神经性疼痛药物靶点的现状研究。药学学报 (Acta Pharmaceutica Sinica) 2017, 52 (3): 355 −361。

专著

1. Yu, H., and Li, M*. High throughput methods for ion channels. Handbook of Ion Channels. Edited by Jie Zheng and Matthew C. Trudeau. CRC Press 2015, Pages 199–210.Print ISBN: 978-1-4665-5140-4. eBook ISBN: 978-1-4665-5142-8. 1万字,2015.
2. Yu, H., Lin, Z., Xu, K., Huang, X., Long, S., Wu, M., McManus, O. B., Engers, J. L., Mattmann, M. E., Engers, D. W., Le, U. M., Lindsley, C. W., *Hopkins, C. R., and *Li, M. Identification of a novel, small molecule activator of KCNQ1 channels. Probe Reports from the NIH Molecular Libraries Program. PMID: 23762928 [PubMed] , 2012.
3. Yu, H., Wu, M., Long, S., *Hopkins, C. R., Engers, J. L., Townsend, S. D., Lindsley, C. W., McManus, O. B., and *Li, M. A small molecule activator of KCNQ2 and KCNQ4 channels. Probe Reports from the NIH Molecular Libraries Program. PMID: 23658954 [PubMed], 2011.
4. Yu, H., Xu, K., Zou, B., Wu, M., McManus, O. B., Engers, J. L., Cheung, Y. Y., Salovich, J. M., *Hopkins, C. R., Lindsley, C. W., and *Li, M. Identification of a novel, small molecule inhibitor of KCNQ2 channels. Probe Reports from the NIH Molecular Libraries Program. PMID: 23658963 [PubMed], 2011.
5. Wu, M., Wang, H., Yu, H., Makhina, E., Xu, J., Dawson, E. S., Hopkins, C. R., *Lindsley, C. W., McManus, O. B., and *Li, M. A potent and selective small molecule Kir2.1 inhibitor. Probe Reports from the NIH Molecular Libraries Program. PMID: 21433384 [PubMed], 2010.

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