科研队伍

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。

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,联合使用高通量实时荧光检测分析系统和细胞电生理记录等体外和体内模型方法,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。

1. Identification of WP1066, an inhibitor of JAK2 and STAT3, as a Kv1.3 potassium channel blocker. Li, M., Yu, H.* Bri J Pharmacol. 2021, 178(13):2617-2631.
2. 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. Sheng,N., Zheng, H., Li,M., Li, M., Wang,Z., Peng, Y., Yu, H.*, Zhang, J*. Pharmacological Research 152 (2020) 104636.
3. 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. Huang,L.*, Ding,J., Li,M., Hou, Z., Geng,Y., Li,X. and Yu, H*. Eur J Med Chem. 2020;185:111824.
4. Three new phenylspirodrimane derivatives with inhibitory effect towards potassium channel Kv1.3 from the fungus Stachybotrys chartarum. Feng, JM., Li, M., Zhao, JL., Jia, XN., Liu, JM., Zhang, M., Chen, RD., Xie, KB., Chen, DW., Yu, HB*, Dai, JG*. J Asian Nat Prod Res. 2019 Sep;21(9):887-894.
5. Identification of WB4101, an alpha1-adrenoceptor antagonist, as a sodium channel blocker. Li, M.#, Wu, Y.#, Zou,B., Wang,XL, Li,M. and Yu, HB*. Mol Pharmacol. 2018, 94(2):896-906. (#,co-first authors)
6. Loperamide inhibits sodium channels to alleviate inflammatory hyperalgesia. Wu, Y#., Zou, B#., Liang, L., Li, M., Tao, Y.-X., Yu, H*., Wang, X*., Li, M*., Neuropharmacology. 2017, 117: 282-291. (#,co-first authors)
7. High throughput screening technologies for ion channels. Yu,HB.*, Li, M., Wang, WP., Wang, XL*. Acta Pharmacol Sin. 2016,37(1):34-43.
8. Investigation of miscellaneous hERG inhibition in large diverse compound collection using automated patch-clamp assay. Yu,HB.*, Zou,BY.*, Wang,XL., Li,M. Acta Pharmacol Sin. 2016,37(1):111-23.
9. Effect of Tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels. Yu, H.*, Zou, B., Wang, X., Li, M. Brit J Pharmacol. 2015, 172(13):3370-82
10. Dynamic Subunit Stoichiometry Confers a Progressive Continuum of Pharmacological Sensitivity by KCNQ Channels. Yu, H., Lin, Z., Mattmann, M., Zou, B., Terrenoire.C., Zhang, H., Wu, M., McManus, O. B., Kass, R. S., Lindsley, C. W., Hopkins, C. R.*, and Li, M*. Proc Natl Acad Sci U S A 110, 2013, 8732-8737.
11. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel. Zhang, H.#, Zou, B. #, Yu, H. #, Moretti, A., Wang, X., Yan, W., Babcock, J. J., Bellin, M., McManus, O. B., Tomaselli, G., Nan, F., Laugwitz, K. L., and Li, M*. Proc Natl Acad Sci U S A. 2012,109, 11866-11871. (# Cofirst author)
12. Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels. Peters,CJ., Yu,H., Tien,J., Jan,YN., Li,M., Jan,LY.*. Proc Natl Acad Sci U S A. 2015 112(11):3547-52.
13. Global analysis reveals families of chemical motifs enriched for HERG inhibitors. Du,F., Babcock,JJ., Yu,H., Zou,B., Li,M*. PLoS One. 2015, 10(2):e0118324.
14. PIP2 alters pharmacological selectivity for epilepsy-causing KCNQ channels. Zhou, P., Yu, H., Gu, M., Nan, F., Gao, Z*, and Li, M*. Proc Natl Acad Sci U S A 110, 8726-8731, 2013.
15. 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. Yu, H., Wu, M., Townsend, S. D., Zou, B., Long, S., Daniels, J. S., McManus, O. B., Li, M*, Lindsley, C. W., and Hopkins, C. R*. ACS chem neurosci 2011, 2, 572-577.
16. 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. Cheung, Y. Y., Yu, H., Xu, K., Zou, B., Wu, M., McManus, O. B., Li, M.*, Lindsley, C. W., and Hopkins, C. R*. J Med Chem 2012, 55, 6975-6979.
17. 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. Mattmann, M. E., Yu, H., Lin, Z., Xu, K., Huang, X., Long, S., Wu, M., McManus, O. B., Engers, D. W., Le, U. M., Li, M.*, Lindsley, C. W., and Hopkins, C. R*. Bioorg Med Chem Lett 2012, 22, 5936-5941.
18. 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. Du, F., Yu, H., Zou, B., Babcock, J., Long, S., and Li, M*.Assay Drug Dev Technol 2011, 9, 580-588.
19. 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. Wang, H. R. #, Wu, M. #, Yu, H., Long, S., Stevens, A., Engers, D. W., Sackin, H., Daniels, J. S., Dawson, E. S., Hopkins, C. R., Lindsley, C. W.*, Li, M.*, and McManus, O. B. ACS Chem Biol 2011, 6, 845-856.
20. Profiling diverse compounds by flux- and electrophysiology-based primary screens for inhibition of human Ether-a-go-go related gene potassium channels. Zou, B., Yu, H., Babcock, J. J., Chanda, P., Bader, J. S., McManus, O. B., and Li, M*. Assay Drug Dev Technol 2010, 8, 743-754.
21. 离子通道作为糖尿病神经性疼痛药物靶点的现状研究。周宇,王晓良,于海波*。药学学报 (Acta Pharmaceutica Sinica) 2017, 52 (3): 355 −361。
22. 大麻二酚在神经精神疾病中的作用与分子机制研究进展。吴军,于海波*。药学学报 (Acta Pharmaceutica Sinica) 2020, 55(12): 2800-2810。
23. 神经病理性疼痛的治疗和药物发现现状。宋佳男,刘玉梅*,于海波*。药学学报 (Acta Pharmaceutica Sinica) 2021, 56(3): 679 −688。
24. 癫痫的治疗和药物发现现状。刘颖,孔令飞*,于海波*。药学学报 (Acta Pharmaceutica Sinica) 2021, 56(4): 924 −938。

1. High throughput methods for ion channels. Handbook of Ion Channels. Yu, H., and Li, M. Edited by Jie Zheng and Matthew C. Trudeau. CRC Press, Pages 199-210. Print ISBN: 978-1-4665-5140-4.
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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