
2014.09–2018.06??山東大學生命科學學院 本科
2018.09–2023.06??清華大學生命科學學院 博士 (導師:施一公)
2023.07–2025.07??清華大學生命科學學院 博士后 (合作導師:施一公)
2025.10–2025.12??德國法蘭克福大學 博士后?(導師:Ivan Dikic)
2026.05–至今??中國科學院上海有機化學研究所 研究員
膜蛋白在細胞中的精確定位與質量控制至關重要,其異常可導致多種疾病的發(fā)生與發(fā)展。本課題組主要利用生物化學與結構生物學手段,系統(tǒng)解析膜蛋白的細胞定位過程及其質量控制系統(tǒng)的分子機制,重點關注膜相關蛋白酶等關鍵因子;并在此基礎上,開發(fā)靶向膜蛋白定位及質量控制過程的小分子化學藥物或大分子蛋白藥物,為相關疾病的治療提供新策略。
2025 清華大學優(yōu)秀博士后
2023 清華大學“水木學者”基金
2018?清華大學“未來學者”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

