张哲，Ph.D，Tenure-track 副教授，研究员，博士生导师，天然药物及仿生药物全国重点实验室PI

地址：北京市海淀区学院路38号北京大学医学部药学楼106室

（邮编：100191）电话：010-62750148            邮箱：zzhang01@pku.edu.cn

实验室网站: https://zzlab.zjwzht.com/

教育经历:

2008年9月-2015年1月，博士，中国科学院上海生命科学研究院生物化学与细胞生物学研究所 2004年9月-2008年6月，本科，山东大学生命科学学院

研究经历:

2026年4月-至今，研究员，北京大学药学院

2019年7月-至今，研究员，北大-清华生命科学联合中心

2019年7月-2026年3月，研究员，北京大学生命科学学院 2015年2月-2019年6月，博士后，美国洛克菲勒大学

研究方向：

课题组长期致力于神经系统疾病及肿瘤相关的膜转运蛋白与受体蛋白的结构与药理机制研究。研究方向聚焦于溶质转运蛋白（SLC）介导的跨膜物质转运，以及膜受体介导的生长与发育信号转导，旨在从分子层面揭示其生理功能与病理机制，并针对关键靶点开展小分子药物筛选与设计，推动神经退行性疾病及癌症等领域的创新药物研发。

在跨膜物质转运方面，系统研究了神经递质与代谢分子的转运机制：揭示了单胺类神经递质和乙酰胆碱的囊泡装载及相关药物的作用机理（Nature 2023; Cell Res. 2024a; Structure 2026）；阐明了多种维生素转运蛋白（如SLC19、SLC33A1）的底物识别与转运机制（Cell Discov. 2022; Cell Res. 2024b; Cell Discov. 2025）；并解析了葡萄糖-6-磷酸转运蛋白SLC37A4的底物转运机制及其小分子抑制剂的作用机理（Nat. Struct. Mol. Biol. 2026）。

在跨膜信号转导方面，聚焦于生长发育与死亡信号的调控机制：解析了轴突退行关键调控蛋白SARM1的分子病理机制（Nature 2020）; 阐明了潜伏态TGF-β1（L-TGF-β1）的呈递与激活过程（Nat. Commun. 2022）；并揭示了EGFR/HER2异源二聚体的组装与信号传导机制（Cell Discov. 2023）及非经典WNT信号复合物VANGL-PRICKLE的组装与功能（Nat. Commun. 2025）。

课题组主要运用冷冻电镜技术解析关键膜蛋白的高分辨率结构，并结合生物化学、细胞生物学及计算生物学等多学科方法，系统阐明其在底物识别、跨膜转运及信号传导中的分子机制。在此基础上，开展基于结构的药物设计与筛选，为相关疾病的新药研发提供重要理论依据。

荣誉奖励:

2025 北京大学优秀共产党员 

2024 兴证全球基金奖教金杰出青年学者奖 

2023 北京大学教学优秀奖 

2022 勃林格殷格翰青年研究员奖 

2021 北京大学生命科学学院最受欢迎教师 

2021 学而思博雅青年学者

2021 中国神经科学重大进展 

2020 拜耳学者 

2019 亿方学者

2018 Blavatnik区域性杰出青年科学家最终提名奖 

2018 Tri-Institutional青年科学家突破奖

代表性论文：

At PKU

#Co-first author, *Corresponding author

- Representative papers

1.Dong Zhou#, Yang Zhang#, Nanhao Chen#, Shitang Huang, Chen Song, and Zhe Zhang; Structural basis of G6P/Pi transport and inhibition in SLC37A4 (2026); Nat. Struct. Mol. Biol. 33(1): 123-133. (doi: 10.1038/s41594-025-01711-5)

2.Yang Zhang and Zhe Zhang*; Structural basis of VAChT inhibition by spiroindolines and alkylsulfones (2026); Structure 34(1): 123-132. (doi: 10.1016/j.str.2025.10.005)

3.Dong Zhou, Nanhao Chen, Shitang Huang, Chen Song, and Zhe Zhang*; Mechanistic insights into the acetyl-CoA recognition by SLC33A1 (2025); Cell Discov. 11(1): 36. (doi: 10.1038/s41421-025-00793-1)

4.Yanyi Song#, Shuyi Jian#, Junlin Teng, Pengli Zheng, and Zhe Zhang; Structural basis of human VANGL-PRICKLE interaction (2025); Nat. Commun. 16(1): 132. (doi: 10.1038/s41467-024-55396-3)

5.Balázs Tóth#, Yuefeng Jiang#, Andras Szollosi, Zhe Zhang, and László Csanády*; A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel (2024); Proc. Natl. Acad. Sci. USA 121(46): e2415548121. (doi: 10.1073/pnas.2415548121)

6.Yang Zhang#, Fei Dai#, Nanhao Chen#, Dong Zhou, Chia-Hsueh Lee, Chen Song, Yixiao Zhang, and Zhe Zhang; Structural insights into VAChT neurotransmitter recognition and inhibition (2024); Cell Res. 34(9): 665-668. (doi: 10.1038/s41422-024-00986-5)

7.Yu Dang#, Tianyi Zhang#, Shabareesh Pidathala#, Guopeng Wang#, Yijie Wang#, Nanhao Chen#, Chen Song, Chia-Hsueh Lee, and Zhe Zhang; Substrates and drug recognition mechanisms of SLC19A3 (2024); Cell Res. 34(6): 458–461. (doi: 10.1038/s41422-024-00951-2)

8.Shabareesh Pidathala#, Shuyun Liao#, Yaxin Dai#, Xiao Li, Changkun Long, Chi-Lun Chang, Zhe Zhang, and Chia-Hsueh Lee; Mechanisms of neurotransmitter transport and drug inhibition in human VMAT2 (2023); Nature 623 (7989): 1086–1092. (doi: 10.1038/s41586-023-06727-9)

9.Fenglian Liu#, Yu Dang#, Lu Li#, Hao Feng#, Jianlin Li, Haowei Wang, Xu Zhang, Zhe Zhang, Sheng Ye, Yutao Tian, and Qingfeng Chen; Structure and mechanism of a neuropeptide-activated channel in the ENaC/DEG superfamily (2023); Nat. Chem. Biol. 19(10): 1276-1285. (doi: 10.1038/s41589-023-01401-7)

10.Xue Bai#, Pengyu Sun#, Xinghao Wang#, Changkun Long#, Shuyun Liao#, Song Dang, Shangshang Zhuang, Yongtao Du, Xinyi Zhang, Nan Li, Kangmin He, and Zhe Zhang; Structure and dynamics of the EGFR/HER2 heterodimer (2023); Cell Discov. 9(1): 18. (doi: 10.1038/s41421-023-00523-5)

11.Yu Dang, Dong Zhou, Xiaojuan Du, Hongtu Zhao, Chia-Hsueh Lee, Jing Yang, Yijie Wang, Changdong Qin, Zhenxi Guo, and Zhe Zhang*; Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022); Cell Discov. 8(1): 141. (doi: 10.1038/s41421-022-00508-w)

12.Zelin Duan#, Xuezhen Lin#, Lixia Wang#, Qiuxin Zhen, Yuefeng Jiang, Chuxin Chen, Jing Yang, Chia-Hsueh Lee, Yan Qin, Ying Li, Bo Zhao, Jianchuan Wang, and Zhe Zhang*; Specificity of TGF-β1 signal designated by LRRC33 and integrin αVβ8 (2022); Nat. Commun. 13(1): 4988. (doi: 10.1038/s41467-022-32655-9)

13.Zhaohan Lin#, Yinglin Li#, Yuqi Hang#, Changhe Wang, Bing Liu, Jie Li, Lili Yin, Xiaohan Jiang, Xingyu Du, Zhongjun Qiao, Feipeng Zhu, Zhe Zhang, Quanfeng Zhang, and Zhuan Zhou*; Tuning the size of large dense-core vesicles and quantal neurotransmitter release via secretogranin II liquid-liquid phase separation (2022); Adv. Sci. e2202263. (doi: 10.1002/advs.202202263)

14.Yuefeng Jiang, Tingting Liu, Chia-Hsueh Lee, Qing Chang, Jing Yang, and Zhe Zhang; The NAD+-mediated self-inhibition mechanism of pro-neurodegenerative SARM1 (2020); Nature 588(7839): 658-663. (doi: 10.1038/s41586-020-2862-z)

- Others

15.Meijiao Wang#, Wencheng Xia#, Dan Zhao, Zhaoyi Zhai, Rongjing Chen, Xue Bai, Zhe Zhang, Hao Fan, Jian-Ping Zhang, Cong Liu, and Fang Jiao*; Amyloid Fibrillation of a Ninjurin-1-Derived α-Helical Peptide: Structural Insights into Conformational Transition (2025); ACS Nano. 19(40): 35977-35991. (doi: 10.1021/acsnano.5c14731)

16.Jing Wang#, Zhengyang An#, Zhongsheng Wu#, Wei Zhou#, Pengyu Sun, Piyu Wu, Song Dang, Rui Xue, Xue Bai, Yongtao Du, Rongmei Chen, Wenxu Wang, Pei Huang, Sin Man Lam, Youwei Ai, Suling Liu, Guanghou Shui, Zhe Zhang, Zheng Liu, Jianyong Huang, Xiaohong Fang, and Kangmin He; Spatial organization of PI3K-PI(3,4,5)P3-AKT signaling by focal adhesions (2024); Mol. Cell 84(22): 4401-4418. (doi: 10.1016/j.molcel.2024.10.010)

17.Xuehui Lyu#, Yingzi Cui#, Yinfei Kong#, Min Yang, Hui Shen, Shuyun Liao, Shiyu Li, Chenrui An, Haoyi Wang, Zhe Zhang, Jennie Ong, Yan Li, and Peng Du*; A transient transcriptional activation governs unpolarized-to-polarized morphogenesis during embryo implantation (2024); Mol. Cell 84(14): 2665-2681. (doi: 10.1016/j.molcel.2024.06.005)

18.Yansong Zhang#, Siyuan Lin#, Jingyu Peng#, Xiaojuan Liang, Qi Yang, Xue Bai, Yajuan Li, Jinhua Li, Wei Dong, Yue Wang, Ying Huang, Yumeng Pei, Jiabao Guo, Wanni Zhao, Zhe Zhang, Min Liu, and Alan Jian Zhu; Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination (2022); Mol. Cell 82(8): 1528-1542. (doi: 10.1016/j.molcel.2022.01.021)

19.Yingdi Wang, Yiming Niu, Zhe Zhang, Kenneth Gable, Sita D Gupta, Niranjanakumari Somashekarappa, Gongshe Han, Hongtu Zhao, Alexander G Myasnikov, Ravi C Kalathur, Teresa M Dunn, and Chia-Hsueh Lee*; Structural insights into the regulation of human serine palmitoyltransferase complexes (2021); Nat. Struct. Mol. Biol. 28(3): 240-248. (doi: 10.1038/s41594-020-00551-9)

Before PKU

20.Fangyu Liu#, Zhe Zhang#, Anat Levit, Jesper Levring, Kouki K. Touhara, Brian K. Shoichet, and Jue Chen*; Structural identification of a hotspot on CFTR for potentiation (2019); Science 364(6446): 1184-1188. (doi: 10.1126/science.aaw7611)

21.Zhe Zhang#, Fangyu Liu#, and Jue Chen*; Molecular structure of the ATP-bound, phosphorylated human CFTR (2018); Proc. Natl. Acad. Sci. USA 115(50): 12757-12762. (doi: 10.1073/pnas.1815287115)

22.Zhe Zhang#, Balazs Tóth#, Andras Szollosi, Jue Chen, and Laszló Csanady; Structure of a TRPM2 channel in complex with Ca2+ explains unique gating regulation (2018); eLife 7: e36409. (doi: 10.7554/eLife.36409)

23.Zhe Zhang, Fangyu Liu, and Jue Chen*; Conformational changes of CFTR upon phosphorylation and ATP binding (2017); Cell 170(3): 483-491.e8. (doi: 10.1016/j.cell.2017.06.041)

24.Fangyu Liu#, Zhe Zhang#, Laszló Csanady, David C Gadsby, and Jue Chen*; Molecular structure of the human CFTR ion channel (2017); Cell 169(1): 85-95.e8. (doi: 10.1016/j.cell.2017.02.024)

25.Zhe Zhang, and Jue Chen*; Atomic structure of the cystic fibrosis transmembrane conductance regulator (2016); Cell 167(6): 1586-1597.e9. (doi: 10.1016/j.cell.2016.11.014)

26.Zhe Zhang#, Shanshan Wang#, Tong Shen, Jiangye Chen, and Jianping Ding*; Crystal structure of the Rab9A-RUTBC2 RBD complex reveals the molecular basis for the binding specificity of Rab9A with RUTBC2 (2014); Structure 22(10): 1408-1422. (doi: 10.1016/j.str.2014.08.005)

27.Zhe Zhang, Tianlong Zhang, Shanshan Wang, Zhou Gong, Chun Tang, Jiangye Chen, and Jianping Ding*; Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5 (2014); eLife 3: e02687. (doi: 10.7554/eLife.02687)

课题组长期招聘博士研究生与博士后，提供系统的科研训练、活跃的学术氛围、具有竞争力的薪酬待遇以及良好的职业发展平台。欢迎有志于膜蛋白结构与药理研究的青年学者申请！有意者请将简历及个人陈述发至zzhang01@pku.edu.cn