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個人簡介
羅雪蓮博士1990年獲得北京大學化學學士學位；1997年獲得塔夫茨大學醫學院生物化學博士學位；1997-1999年在哈佛醫學院從事博士后研究，1999-2001年在德克薩斯大學西南醫學中心從事博士后研究；2001年、2004年歷任德克薩斯大學西南醫學中心講師、助理教授。羅雪蓮博士2006年在德克薩斯大學西南醫學中心藥理學系開始其獨立研究生涯，2015年晉升為終身副教授。羅雪蓮博士于2024年11月加入西湖大學并擔任正教授,?博士生導師。
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學術成果及研究方向
羅雪蓮博士的實驗室致力于利用生化、結構和細胞學方法相結合的研究手段，來了解細胞內信號傳導途徑的分子機制。她目前的研究工作重點在調控器大小和維持組織穩態的Hippo途徑的機制和調控上。該研究為核心MST-LATS激酶級聯和TEAD-YAP在Hippo信號傳導過程中的激活機制和調控提供了重要的見解：1）工作闡明了MOB1介導MST依賴的LATS激活的機制，這是Hippo信號傳導過程中的一個關鍵。展示了LATS的激活需要依次進行多步驟的MST依賴的磷酸化。MOB1通過動態支架和變構機制介導LATS的激活。2）研究揭示了MST被SAV1激活的關鍵機制，通過拮抗STRIPAK-PP2A磷酸酶。STRIPAK是Hippo途徑的一個關鍵負調控因子。最近確定了人類STRIPAK-PP2A復合物的冷凍電鏡結構。研究揭示了STRIPAK在蛋白質磷酸酶中處于巔峰地位，具有一個異常復雜的蛋白質網絡，可調節多樣的細胞信號傳導。3）研究發現TEAD轉錄因子具有功能上重要的自酰化修飾。發現表明TEAD具有類酶活性，這表明先前被認為無法靶向的TEAD-YAP實際上是一種吸引人的癌癥治療分子靶點。羅雪蓮博士的研究旨在推動人們對Hippo信號傳導網絡調控的基礎認識，并揭示利用Hippo途徑缺陷治療人類疾病的新途徑。
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代表論文
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) p31comet?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)
聯系方式
luoxuelian@westlake.edu.cn
