2014.09–2018.06  山东大学生命科学学院 本科

2018.09–2023.06  清华大学生命科学学院 博士 （导师：施一公）

2023.07–2025.07  清华大学生命科学学院 博士后 （合作导师：施一公）

2025.10–2025.12  德国法兰克福大学 博士后 （导师：Ivan Dikic）

2026.05–至今  中国科学院上海有机化学研究所 研究员

膜蛋白在细胞中的精确定位与质量控制至关重要，其异常可导致多种疾病的发生与发展。本课题组主要利用生物化学与结构生物学手段，系统解析膜蛋白的细胞定位过程及其质量控制系统的分子机制，重点关注膜相关蛋白酶等关键因子；并在此基础上，开发靶向膜蛋白定位及质量控制过程的小分子化学药物或大分子蛋白药物，为相关疾病的治疗提供新策略。

2025 清华大学优秀博士后

2023 清华大学“水木学者”基金

2018 清华大学“未来学者”基金

1. Xuefei Guo, Haotian Li, Chuangye Yan, Jianlin Lei, Rui Zhou*, and Yigong Shi*. "Molecular Mechanism of Substrate Recognition and Cleavage by Human Gamma-Secretase." Science 384, no. 6700 (Jun 7 2024): 1091-95. https://doi.org/10.1126/science.adn5820.

2. Xuefei Guo#, Haotian Li, Xiaoli Lu, Hao Liu, Kaicheng U, Chuangye Yan, Jianlin Lei, Jing Huang, Rui Zhou#* and Yigong Shi*. "Structural Basis of Human Gamma-Secretase Inhibition by Anticancer Clinical Compounds." Nat Struct Mol Biol  (Dec 9 2024). https://doi.org/10.1038/s41594-024-01439-8.

3. Xuefei Guo#, Yumeng Wang#, Jiaoyao Zhou, Chen Jin, Jiaoni Wang, Bojun Jia, Dan Jing, Rui Zhou#*, and Yigong Shi*. "Molecular Basis for Isoform-Selective Inhibition of Presenilin-1 by MRK-560." Nat Commun 13, no. 1 (Oct 22 2022): 6299. https://doi.org/10.1038/s41467-022-33817-5.

4. Guanghui Yang#, Rui Zhou#, Xuefei Guo#, Chuangye Yan, Jianlin Lei, and Yigong Shi*. "Structural Basis of Gamma-Secretase Inhibition and Modulation by Small Molecule Drugs." Cell 184, no. 2 (Jan 21 2021): 521-33 e14. https://doi.org/10.1016/j.cell.2020.11.049. #co-first author

5. Gaoxingyu Huang#, Xuefei Guo#, Jiaoni Wang#, et al. Structural insights into human signal peptide peptidase. Proc Natl Acad Sci U S A. 2025;122(51):e2528340122. https://doi.org/10.1073/pnas.2528340122 

6. Rui Zhou#, Guanghui Yang#, Xuefei Guo, Qiang Zhou, Jianlin Lei, and Yigong Shi*. "Recognition of the Amyloid Precursor Protein by Human Gamma-Secretase." Science 363, no. 6428 (Feb 15 2019). https://doi.org/10.1126/science.aaw0930.

7. Guanghui Yang#., Rui Zhou#, Qiang Zhou, Xuefei Guo, Chuangye Yan, Meng Ke, Jianlin Lei, and Yigong Shi*. "Structural Basis of Notch Recognition by Human Gamma-Secretase." Nature 565, no. 7738 (Jan 2019): 192-97. https://doi.org/10.1038/s41586-018-0813-8.

8. Scholes, N. S., Bertoni, M., Comajuncosa-Creus, A., Kladnik, K., Guo, X., Frommelt, F., … Winter, G. E. (2025). Inhibitors supercharge kinase turnover through native proteolytic circuits. Nature, 10.1038/s41586-025-09763-9. Advance online publication. https://doi.org/10.1038/s41586-025-09763-9