个人简介

罗雪莲博士1990年获得北京大学化学学士学位；1997年获得塔夫茨大学医学院生物化学博士学位；1997-1999年在哈佛医学院从事博士后研究，1999-2001年在德克萨斯大学西南医学中心从事博士后研究；2001年、2004年历任德克萨斯大学西南医学中心讲师、助理教授。罗雪莲博士2006年在德克萨斯大学西南医学中心药理学系开始其独立研究生涯，2015年晋升为终身副教授。罗雪莲博士将于2024年11月加入西湖大学并担任正教授,博士生导师。

学术成果及研究方向

罗雪莲博士的实验室致力于利用生化、结构和细胞学方法相结合的研究手段，来了解细胞内信号传导途径的分子机制。她目前的研究工作重点在调控器大小和维持组织稳态的Hippo途径的机制和调控上。该研究为核心MST-LATS激酶级联和TEAD-YAP在Hippo信号传导过程中的激活机制和调控提供了重要的见解：1）工作阐明了MOB1介导MST依赖的LATS激活的机制，这是Hippo信号传导过程中的一个关键。展示了LATS的激活需要依次进行多步骤的MST依赖的磷酸化。MOB1通过动态支架和变构机制介导LATS的激活。2）研究揭示了MST被SAV1激活的关键机制，通过拮抗STRIPAK-PP2A磷酸酶。STRIPAK是Hippo途径的一个关键负调控因子。最近确定了人类STRIPAK-PP2A复合物的冷冻电镜结构。研究揭示了STRIPAK在蛋白质磷酸酶中处于巅峰地位，具有一个异常复杂的蛋白质网络，可调节多样的细胞信号传导。3）研究发现TEAD转录因子具有功能上重要的自酰化修饰。发现表明TEAD具有类酶活性，这表明先前被认为无法靶向的TEAD-YAP实际上是一种吸引人的癌症治疗分子靶点。罗雪莲博士的研究旨在推动人们对Hippo信号传导网络调控的基础认识，并揭示利用Hippo途径缺陷治疗人类疾病的新途径。

代表论文

1.Luo, X., Tang, Z., Xia, G., Wassmann, K., Matsumoto, T., Rizo, J., & Yu, H. (2004) The Mad2 Spindle Checkpoint Protein Has Two Distinct Natively Folded States.Nat. Struct. Mol. Biol.,4, 338-45.

2.Yang, M., Li, B., Tomchick, DR., Machius, M., Rizo, J., Yu, H. &Luo, X. (2007) p31^comet Blocks Mad2 Activation through Structural Mimicry.Cell,131, 744-755. PMCID: PMC2144745

3.Yang, M., Li, B., Liu, C., Tomchick, D.R., Machius, M., Rizo, J., Yu, H. &Luo, X. (2008) Insights into Mad2 Regulation in the Spindle Checkpoint Revealed by the Crystal Structure of the Symmetric Mad2 dimer.PLoS Biol.,6, 643-655. PMCID: PMC2270309

4.Tian, W., Yu, J., Tomchick, D., Pan, D. &Luo, X. (2010) Structural and Functional Analysis of the YAP-binding Domain of Human TEAD2.Proc. Natl. Acad. Sci. U.S.A.,107, 7293-8. PMCID: PMC2867681

5.Kim, S., Sun, H., Tomchick, D.R., Yu, H., &Luo, X. (2012) Structure of Human Mad1 C-terminal Domain Reveals Its Kinetochore-Targeting Function.Proc. Natl. Acad. Sci. U.S.A., 109, 6549-54. (covered in Research Highlights article, “Mad1 attachment” by M. Montoya, Nat. Struct. Mol. Biol. 19 (2012): 470). PMCID: PMC3340083

6.Tian, W., Li, B., Warrington, R., Tomchick, D.R., Yu, H. &Luo, X. (2012) Structural Analysis of Human Cdc20 Supports Multi-site Degron Recognition by APC/C.Proc. Natl. Acad. Sci. U.S.A.,109, 18419-24. PMCID: PMC3494910

7.Ni, L., Li, S., Yu, J., Min, J., Brautigam, C.A., Tomchick, D.R., Pan, D. & Luo, X. (2013) Structural Basis for Autoactivation of Human Mst2 Kinase and Its Dual Regulation by RASSF5.Structure,21, 1757-68. PMCID: PMC3797246

8.Sackton, K., Dimova, N., Zeng, X., Tian, W., Zhang, M., Sackton, T., Meaders, J., Pfaff, K., Sigoillot, F., Yu, H.,Luo, X., & King, R.W. (2014) Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C.Nature,514, 646-649. PMCID: PMC4214887

9.Ni, L., Zheng, Y., Hara, M., Pan, D. &Luo, X. (2015) Structural Basis for Mob1-Dependent Activation of the Core Mst-Lats Kinase Cascade in Hippo Signaling.Genes Dev.,29, 1416-31. PMCID: PMC4511216

10.Hara, M., Ozkan, E., Sun, H., Yu, H. &Luo, X. (2015) Structure of an Intermediate Conformer of the Spindle Checkpoint Protein Mad2.Proc. Natl. Acad. Sci. U.S.A.,112, 11252-7. PMCID: PMC4568698

11.Pobbati, A.V.*, Han, X., Hung, A.W., Weiguang, S., Huda, N., Chen, G., Kang, C., Chia, C.,Luo, X.*, Hong, W. & Poulsen, A.* (2015) Targeting the Central Pocket in Human Transcription Factor TEAD as a Potential Cancer Therapeutic Strategy.Structure,23, 2076-86. PMCID: PMC4660270 (*Corresponding authors)

12.Chan, P., Han, X., Zheng, B., DeRan, M., Yu, J., Jarugumilli, G.K., Deng, H., Pan, D.,Luo, X.* & Wu, X.* (2016) Autopalmitoylation of TEAD Proteins Regulates Transcriptional Output of the Hippo Pathway.Nat Chem Biol.,12, 282-9.PMCID: PMC4798901 (*Corresponding authors)

13.Lin, Z.,Luo, X. & Yu, H. (2016) Structural Basis of Cohesin Cleavage by Separase.Nature,532, 131-4. PMCID: PMC4847710

14.Ouyang, Z., Zheng, G., Tomchick, D.R.,Luo, X. & Yu, H. (2016) Structural Basis and IP₆ Requirement for Pds5-Dependent Cohesin Dynamics.Mol. Cell,62, 248-59. PMID:26971492

15.Bae, S.J., Ni, L., Osinski, A., Tomchick, D.R., Brautigam, C.A. &Luo, X. (2017) SAV1 Promotes Hippo Kinase Activation through Antagonizing the PP2A Phosphatase STRIPAK.Elife,6:e30278. PMCID: PMC5663475

16.Brulotte, M.L., Jeong, B., Li, F., Li, B., Yu, E.B., Wu, Q., Brautigam, C.A., Yu, H. &Luo, X. (2017) Mechanistic Insight into TRIP13-catalyzed Mad2 Structural Transition and Spindle Checkpoint Silencing.Nat Commun., 8:1956. PMCID: PMC5717197

17.Bae, S.J., Ni, L. &Luo, X. (2020) STK25 Suppresses Hippo Signaling by Regulating SAV1-STRIPAK.Elife, doi:10.7554/eLife.54863. PMCID: PMC7182433

18.Jeong, B., Bae, S.J., Ni, L., Zhang, X., Bai, X. & Luo, X. (2021) Cryo-EM Structure of the Hippo Signaling Integrator Human STRIPAK.Nat Struct Mol Biol., 28:290-299. PMCID: PMC8315899 (Featured in News & Views)

19.Hu, L., Sun, Y., Liu, S., Erb, H., Singh, A., Mao, J., Luo, X.* & Wu, X.* (2022) Discovery of a new class of reversible TEA domain transcription factor inhibitors with a novel binding mode.Elife, doi: 10.7554/eLife.80210. PMCID: PMC9728997 (*Corresponding authors)

联系方式

luoxuelian@westlake.edu.cn