游慧娟

游慧娟

职称及职务：教授，博士硕士生导师

研究方向：分子药理学，单分子生物物理,核酸的结构和功能。

邮箱：youhuijuan@@hust.edu.cn

地址：武汉市航空路13号同济医学院060net永利三号楼206室

工作经历

2016.12-至今永利官网同济060net永利教授

2013.6-2016.12新加坡国立大学博士后导师：严洁

2011.10-2013.3东京大学研究助理导师：Noji, Hiroyuki

教育经历：

2001.9-2006.7北京大学理学学士(生命科学)

2006.10-2008.9大阪大学工学硕士（生物技术）

2008.10-2012.11大阪大学工学博士（生物技术）

近五年科研项目：

国家自然科学基金面上项目,32571415,单分子磁镊研究超稳定的RNA G-四链体折叠动态及细胞微环境调控折叠的分子机理, 2026-2029, 50万元,主持

国家自然科学基金面上项目, 32171225,天然产物来源DNA加合物的不同结合模式导致DNA损伤机制的单分子力谱研究, 2022-2025, 58万元,主持

简介：

G-四链体核酸的结构和功能及靶向G-四链体的小分子化合物：G-四链体DNA和RNA是一种富含鸟嘌呤的四链核酸二级结构。具有生物功能的G-四链体核酸是癌症和衰老，病毒，以及神经退行性疾病的有前景的药物靶点。课题组发展了单分子磁镊方法实现对单个核酸分子纳米精度折叠动态的长时间的连续观察,系统地研究G-四链体的折叠动态,并拓展了单分子方法在新颖活性天然产物的新药发现研究中的应用。在JACS, Nucleic Acids Research, J. Phys. Chem. Lett.，JBC等期刊发表学术论文多篇。

发表论文（#同等贡献；*通讯作者）

1. Cheng Y., Wang X., Yang X.,Zhang, Y.,You, H.Impact of a single 8-oxoguanine lesion on Watson–Crick and Hoogsteen base pair hybridization in telomeric DNA quantified using single-molecule force spectroscopy. Nucleic Acids Research, 2025, 53(11): gkaf508.

2. Zhang, Y., Cheng, Y., Luo, Q., Wu, T., Huo, J., Yin, M., Peng, H., Xiao, Y., Tong, Q^*.,You, H^*. Distinguishing G-Quadruplexes Stabilizer and Chaperone for c-MYC Promoter G-Quadruplexes through Single-Molecule Manipulation.Journal of the American Chemical Society,2024,146(6), 3689-3699.

3. Liu, T., Cai, T., Huo, J., Liu, H., Li, A., Yin, M.,Mei,Y., Zhou, Y., Fan, S., Lu, Y., Wan, L.,You, H^*., Cai, X^*.. Force-enhanced sensitive and specific detection of DNA-intercalative agents directly from microorganisms at single-molecule level.Nucleic Acids Research, 2024,52(18), e86-e86.

4. Li, Z., Hu, R., Li, T., Zhu, J.,You, H., Li, Y.,Liu, B., Li, C., Li, Y., Yang, Y. A TeZla micromixer for interrogating the early and broad folding landscape of G-quadruplex via multistage velocity descending.Proceedings of the National Academy of Sciences of the United States of America, 2024, 121(4),e2315401121-e2315401121.

5. Liu, T., Wu, Y., Qin, L., Luo, Q., Li, W., Cheng, Y.,Tu, Y^*.,You, H^*. Nonselective Intercalation of G-Quadruplex-Targeting Ligands into Double-Stranded DNA Quantified by Single-Molecule Stretching.The Journal of Physical Chemistry B, 2023,127(26), 5859-5868.

6. Liu, Y.,Pei, Y.,Xu, J.,Cheng, Y.,Tong, Q.,You, H^*; Force-Dependent Intercalative Bulky DNA Adduct Formation Detected by Single-Molecule Stretching.Analytical Chemistry, 2022, 94(39),13623-30.

7. Zhang, Y., Cheng, Y., Chen, J., Zheng K*.,You, H*. Mechanical diversity and folding intermediates of parallel-stranded G-quadruplexes with a bulge.Nucleic Acids Research, 2021, 49(12), 7179-7188

8. Cheng, Y.,Zhang,Y., Gong, Z., Zhang, X., Li,Y., Shi, X., Yufeng Pei.,You, H*.High Mechanical Stability and Slow Unfolding Rates Are Prevalent in Parallel-Stranded DNA G-Quadruplexes.The Journal of Physical Chemistry Letters, 2020, 11(19),7966-7971.

9. Pei, Y., Liu, Y., Xie, C., Zhang, X.,You, H*.Detecting the Formation Kinetics of Doxorubicin-DNA Interstrand Cross-link at the Single-Molecule Level and Clinically Relevant Concentrations of Doxorubicin.Analytical Chemistry. 2020, 92 (6), 4504-4511.

10. Li, X., Pei, Y., Zhang, Y., Liu, Y., Fu, W., Li, J.,You,H*., Huang, J*. (2020). Single-Molecule Mechanical Unfolding of AT-Rich Chromosomal Fragile Site DNA Hairpins: Resolving the Thermodynamic and Kinetic Effects of a Single GT Mismatch.The Journal of Physical Chemistry B, 124(42), 9365-9370.

11. Cheng, Y., Tang, Q., Li, Y., Zhang, Y., Zhao, C., Yan, J.,You, H*. Folding/unfolding kinetics of G-quadruplexes upstream of the P1 promoter of the human BCL-2 oncogene.Journal of Biological Chemistry. 2019, 294 (15), 5890-5895.

12. Tong, Q^#.,You, H^#., Chen, X., Wang, K., Sun, W., Pei, Y., Zhao, X.,Yuan, M., Zhu, H., Luo, Z^*., Zhang, Y^*. ZYH005, a novel DNA intercalator, overcomes all-trans retinoic acid resistance in acute promyelocytic leukemia.Nucleic Acids Research. 2018,46(7): 3284-3297.

13. You, H^#., Guo, S^#., Le, S., Tang, Q., Yao, M., Zhao, X., & Yan, J. Two-State Folding Energy Determination Based on Transition Points in Non-Equilibrium Single-Molecule Experiments.The journal of physical chemistry letters.2018, 9 (4), 811–816.

14. You, H^#., Lattmann, S^#., Rhodes, D^*., Yan, J^*. RHAU helicase stabilizes G4 in its nucleotide-free state and destabilizes G4 upon ATP hydrolysis.Nucleic Acids Research, 2017, 45(1): 206-214.

15. Iino, R^*., Iida, T., Nakamura, A.,You, H^*., Saita, E., Sako, Y^*. Single-molecule imaging and manipulation of biomolecular machines and systems.Biochimica et Biophysica Acta (BBA) - General Subjects, 2018.2.1, 1862(2): 241~252.

16. You, H^#*., Le, S^#., Chen, H., Qin, L., & Yan, J^*. Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers.Journal of visualized experiments: JoVE, 2017 (127).

17. You, H., Wu, J., Shao, F., & Yan, J.Stability and kinetics of c-MYC promoter G-quadruplexes studied by single-molecule manipulation.Journal of the American Chemical Society, 2015, 137 (7), 2424-2427.

18. You, H., Zeng, X., Xu, Y., Lim C.J, Efremov, A., Phan A.T, Yan J. Dynamics and stability of polymorphic human telomeric G-quadruplex under tension.Nucleic Acids Research.2014, 42 (13), 8789-8795.

19. You, H., Iino, R., Watanabe, R., Noji, H. Winding single-molecule double-stranded DNA on a nanometer-sized reel.Nucleic Acids Research.2012 40 (19): e151.

20. Yang, Y.,Song, L.,Zhao, X., Zhang, C., Wu, W.,You, H., Fu, H., Zhou, E., Zhang, X. A Universal Assay for Making DNA, RNA, and RNA-DNA Hybrid Configurations for Single-Molecule Manipulation in Two or Three Steps without Ligation.ACS synthetic biology. 2019, 8 (7), 1663-1672

21. Zhang, C., Fu, H., Yang, Y., Zhou, E., Tan, Z.,You, H., Zhang, X. The mechanical properties of RNA-DNA hybrid duplex stretched by magnetic tweezers.Biophysical journal. 2019, 116 (2), 196-204

22. Guo, S., Tang, Q., Yao, M.,You, H., Le, S., Chen, H., & Yan, J. Structural-elastic determination of the force-dependent transition rate of biomolecules.Chemical Science. 2018, 9, 5871-5882.

23. Watanabe, R., Koyasu, K.,You, H., Tanigawara, M., Noji, H. Torque transmission mechanism via DELSEED loop of F1-ATPase.Biophysical Journal2015, 108 (5), 1144-1152.

24. Cheng, Y., Zhang, Y., &You, H^*. Characterization of G-Quadruplexes Folding/Unfolding Dynamics and Interactions with Proteins from Single-Molecule Force Spectroscopy.Biomolecules, 2021，11(11), 1579.

25. Yang, J., Wan, S. Y., Song, Q. Y., Xie, Y. H., Wan, J., Zhou, Y. H., ... & Huang, K. Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates.Cell Death &Differentiation, 2025，32(4), 672-688.

    英文专著

    You, H., Zhou, Y., & Yan, J. (2021). Using Magnetic Tweezers to Unravel the Mechanism of the G-quadruplex Binding and Unwinding Activities of DHX36 Helicase. InRNA Remodeling Proteins(pp. 175-191). Humana, New York, NY.