研究员

博士生导师

个人简介

我的主要研究方向为与代谢类疾病和心血管疾病密切相关的重要蛋白，特别是离子通道等膜蛋白的工作机制。我们实验室以结构生物学、生物化学、细胞生物学、生物物理、电生理等方法来研究这些蛋白工作的机理。我以通讯作者在Nature和Cell等杂志上发表论文若干篇，解析了ATP敏感的钾离子通道和一氧化氮受体可溶性鸟苷酸环化酶等蛋白的工作机制。

所授课程

本科生研究生合上：

《蛋白质结构分析》

研究生：

《离子通道门控机制研究进展》

《膜蛋白研究前沿进展研讨》

教育背景

2001-2005 清华大学生物科学与技术系 本科

2005-2010 清华大学生命科学学院 博士

工作简历

2010–2016 美国俄勒冈健康与科学大学 博士后

2016–现在  北京大学未来技术学院 研究员 博士生导师

承担项目

n 国家自然科学基金优秀青年项目 (课题负责人，项目编号31622021，“离子通道门控机制”，130万，2017.1-2019.12)

n 国家自然科学基金面上项目 （课题负责人，项目编号31870833，“KATP通道激活机制的研究”，59万，2019.1-2022.12）

n 国家自然科学基金重大研究计划重点支持项目（课题负责人，项目编号 91957201, “二型糖尿病重要药物靶点的结构机制研究”,316万，2020.1-2023.12）

代表性论文

Y. Kang and L. Chen. Structural basis for the binding of DNP and purine nucleotides onto UCP1. in Nature, 2023, 2023/06/20 edn Vol. 620 226-231.

2. Y. Yang and L. Chen. Functional dissection of KATP channel structures reveals the importance of a conserved interface. in Structure, 2023, 20231201 edn.

3. D. Ding, T. Hou, M. Wei, J. X. Wu and L. Chen. The inhibition mechanism of the SUR2A-containing K(ATP) channel by a regulatory helix. in Nat Commun, 2023, 2023/06/18 edn Vol. 14 3608.

4. W. Cui, Y. Niu, Z. Sun, R. Liu and L. Chen. Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. in Nat Commun, 2023, 2023/05/23 edn Vol. 14 2920.

5. R. Liu, Y. Kang and L. Chen. NO binds to the distal site of haem in the fully activated soluble guanylate cyclase. in Nitric Oxide, 2023, 2023/03/28 edn Vol. 134-135 17-22.

6. R. Liu, K. Song, J. X. Wu, X. P. Geng, L. Zheng, X. Gao, H. Peng and L. Chen. Structure of human phagocyte NADPH oxidase in the resting state. in Elife, 2022, 2022/11/23 edn Vol. 11.

7. Y. Niu, W. Cui, R. Liu, S. Wang, H. Ke, X. Lei and L. Chen. Structural mechanism of SGLT1 inhibitors. in Nat Commun, 2022, 2022/10/29 edn Vol. 13 6440.

8. X. He, Y. Kang and L. Chen. Identification of ASPDH as a novel NAADP-binding protein. in Biochem Biophys Res Commun, 2022, 2022/07/17 edn Vol. 621 168-175.

9. Y. Yang, M. Wei and L. Chen. Structural identification of riluzole-binding site on human TRPC5. in Cell Discov, 2022, 2022/07/13 edn Vol. 8 67.

10. M. Wang, J. X. Wu and L. Chen. Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. in Front Pharmacol, 2022, 2022/07/19 edn Vol. 13 929684.

11. D. Ding, J. X. Wu, X. Duan, S. Ma, L. Lai and L. Chen. Structural identification of vasodilator binding sites on the SUR2 subunit. in Nat Commun, 2022, 2022/05/14 edn Vol. 13 2675.

12. M. Wang, J. X. Wu, D. Ding and L. Chen. Structural insights into the mechanism of pancreatic KATP channel regulation by nucleotides. in Nat Commun, 2022, 2022/05/19 edn Vol. 13 2770.

13. Y. Kang and L. Chen. Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex. in Nat Commun, 2022, 2022/05/14 edn Vol. 13 2639.

14. W. Guo, M. Wang and L. Chen. A co-expression vector for baculovirus-mediated protein expression in mammalian cells. in Biochem Biophys Res Commun, 2022, 2022/01/26 edn Vol. 594 69-73.

15. W. Guo, Q. Tang, M. Wei, Y. Kang, J. X. Wu and L. Chen. Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. in Neuron, 2022, 2022/01/21 edn Vol. 110 1023-1035 e5.

16. Y. Niu, R. Liu, C. Guan, Y. Zhang, Z. Chen, S. Hoerer, H. Nar and L. Chen. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. in Nature, 2021, 2021/12/08 edn Vol. 601 280-284.

17. R. Liu, Y. Kang and L. Chen. Activation mechanism of human soluble guanylate cyclase by stimulators and activators. in Nat Commun, 2021, Vol. 12 5492.

18. K. Song, M. Wei, W. Guo, L. Quan, Y. Kang, J. X. Wu and L. Chen. Structural basis for human TRPC5 channel inhibition by two distinct inhibitors. in Elife, 2021, 2021/03/09 edn Vol. 10.

19. J. X. Wu, R. Liu, K. Song and L. Chen. Structures of human dual oxidase 1 complex in low-calcium and high-calcium states. in Nat Commun, 2021, 2021/01/10 edn Vol. 12 155.

20. C. Guan, Y. Niu, S. C. Chen, Y. Kang, J. X. Wu, K. Nishi, C. C. Y. Chang, T. Y. Chang, T. Luo and L. Chen. Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. in Nat Commun, 2020, 2020/05/20 edn Vol. 11 2478.

21. Y. Kang, J. X. Wu and L. Chen. Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex. in Nat Commun, 2020, 2020/12/05 edn Vol. 11 6199.

22. J. X. Wu and L. Chen. Recent Progress on The Studies of OSCA/TMEM63 Family Ion Channels. in Progress in Biochemistry and Biophysics, 2020, Vol. 47 123-130.

23. Y. Kang, R. Liu, J. X. Wu and L. Chen. Structural insights into the mechanism of human soluble guanylate cyclase. in Nature, 2019, 2019/09/13 edn Vol. 574 206-210.

24. W. Guo and L. Chen. Recent progress in structural studies on canonical TRP ion channels. in Cell Calcium, 2019, 2019/09/07 edn Vol. 83 102075.

25. D. Ding, M. Wang, J. X. Wu, Y. Kang and L. Chen. The Structural Basis for the Binding of Repaglinide to the Pancreatic KATP Channel. in Cell Rep, 2019, 2019/05/09 edn Vol. 27 1848-1857 e4.

26. M. Zhang, D. Wang, Y. Kang, J. X. Wu, F. Yao, C. Pan, Z. Yan, C. Song and L. Chen. Structure of the mechanosensitive OSCA channels. in Nat Struct Mol Biol, 2018, 2018/09/08 edn Vol. 25 850-858.

27. J. X. Wu, D. Ding, M. Wang, Y. Kang, X. Zeng and L. Chen. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels. in Protein Cell, 2018, 2018/03/30 edn Vol. 9 553-567.

28. Q. Tang, W. Guo, L. Zheng, J. X. Wu, M. Liu, X. Zhou, X. Zhang and L. Chen. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. in Cell Research, 2018, 2018/04/28 edn Vol. 28 746-755.

29. N. Li, J. X. Wu, D. Ding, J. Cheng, N. Gao and L. Chen. Structure of a Pancreatic ATP-Sensitive Potassium Channel. in Cell, 2017, 2017/01/14 edn Vol. 168 101-110 e10.

30. K. L. Durr, L. Chen, R. A. Stein, R. De Zorzi, I. M. Folea, T. Walz, H. S. McHaourab and E. Gouaux. Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. in Cell, 2014, 2014/08/12 edn Vol. 158 778-792.

31. L. Chen, K. L. Durr and E. Gouaux. X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. in Science, 2014, 2014/08/12 edn Vol. 345 1021-6.

32. L. Chen, F. J. Xin, J. Wang, J. Hu, Y. Y. Zhang, S. Wan, L. S. Cao, C. Lu, P. Li, S. F. Yan, D. Neumann, U. Schlattner, B. Xia, Z. X. Wang and J. W. Wu. Conserved regulatory elements in AMPK. in Nature, 2013, 2013/06/15 edn Vol. 498 E8-10.

33. L. Chen, J. Wang, Y. Y. Zhang, S. F. Yan, D. Neumann, U. Schlattner, Z. X. Wang and J. W. Wu. AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. in Nature Structural and Molecular Biology, 2012, 2012/06/05 edn Vol. 19 716-8.

34. L. Chen, Z. H. Jiao, L. S. Zheng, Y. Y. Zhang, S. T. Xie, Z. X. Wang and J. W. Wu. Structural insight into the autoinhibition mechanism of AMP-activated protein kinase. in Nature, 2009, 2009/05/29 edn Vol. 459 1146-9.