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号同济医学院药学院三号楼206室
工作经历
2016.12-至今 华中科技大学同济药学院 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, 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
国家自然科学基金青年项目, 21708009,端粒和癌基因启动子G-四链体特异性的靶向药物的单分子研究, 2018-2020, 23万元，主持
讲授课程：
《药理学》《药学导论》《应用药理学》
主要研究内容：
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。课题组用单分子生物物理的方法研究G-四链体核酸的结构与功能（JACS2024,NAR2021，JPCL2020，JBC2019，JACS2015，NAR2014），解旋酶对G-四链体的调控（NAR2017）。
靶向核酸的抗肿瘤药物的单分子研究：课题组致力于开发基于单分子操作技术的检测分子间的相互作用的方法，并且将其应用于药理学研究，药物检测筛选。在这一领域的具体工作参见天然产物中发现的新活性化合物的抗癌作用机制研究（NAR2018）。单分子检测阿霉素链间交联DNA及对这一机制在抗肿瘤中作用的重新评价（Anal Chem2020,Anal Chem2022）。
发表论文（#同等贡献；*通讯作者）
1. Zhang, Y., Cheng, Y., Luo, Q., Wu, T., Huo, J., Yin, M., Peng, H., Xiao, Y., Tong, Q*. andYou, 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.
2. 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.
3. 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.
4. 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
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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).
14. 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.
15. 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.
16. 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.
17. 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
18. 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
19. 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.
20. 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.
21. Cheng, Y., Zhang, Y., &You, H*. (2021) Characterization of G-Quadruplexes Folding/Unfolding Dynamics and Interactions with Proteins from Single-Molecule Force Spectroscopy.Biomolecules, 11(11), 1579.
英文专著
1. 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. In RNA Remodeling Proteins (pp. 175-191). Humana, New York, NY.
