Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

WU Beili got her Ph. D. degree at Tsinghua University, Beijing in 2006, and worked as a postdoctoral fellow at The Scripps Research Institute in La Jolla, California from 2007 to 2011. She is currently a Professor at Shanghai Institute of MateriaMedica (SIMM), CAS. Dr. Wu has been focused on protein structural biology, studying protein structure and function relations by solving high-resolution protein crystal structures for over ten years. Her current research is focused on structural studies of G protein-coupled receptors (GPCRs), aiming to understand the molecular mechanisms of signal recognition and transduction by different GPCRs, and providing clues about next generation GPCRdrug discovery. She has established a GPCR structural biology research platform at SIMM, and is making great progress on structural studies of many key GPCRs.

EDUCATION
09/01/1997– 07/31/2001, Beijing Normal University, BA
09/01/2001– 07/31/2006, Tsinghua University, Ph.D.

WORK EXPERIENCE

04/01/2007– 07/18/2011, The Scripps Research Institute, La Jolla, US , Post Doctor
07/19/2011 till now, Shanghai Institute of MateriaMedica, CAS, Professor
12/01/2012 till now, ShanghaiTech University, Invited Professor

Research Directions

Prof. WU Beili's research is focused on structural biology studies of GPCRs by solving high-resolution crystal structures of different GPCRs to study structure-function relations of GPCRs and perform structure-based drug design and discovery. Her futureresearch directions include:
1. Structuredetermination of complexes between GPCRs and novel ligands
2. Structure determination of complexes between GPCRs and endogenous protein ligands
3. Structure determination of GPCRs withoutstructural information

Grants & Research Projects

1. NIH, R01 Molecular Mechanism of HIV Entry Mediated by Chemokine Receptor CCR5, Project Leader, 2012.2-2017.1
2. 973, Ministry of Science and Technology(MOST), China, Basic Research on GPCR Drug Targets Involved in Cardiovascular Diseases, Sub-project Leader, 2012.1-2016.12
3. 973, Ministry of Science and Technology(MOST), China, Novel Technology and Method Research in Structural Biology Studies of Protein Complexes and Membrane Proteins, Participant, 2014.1-2018.12
4. National Science and Technology Major Project, Ministry ofScience and Technology(MOST), China, GPCR Structure and Function-based Drug Discovery, Participant, 2013.1-2015.12
5. National Science and Technology Major Project, Ministry ofScience and Technology(MOST), China, Key Technology Development and Platform Construction in GPCR Structure and Function-based Drug Discovery, Participant, 2012.1-2015.12
6. Special Leading Science and Technology Project (type B), CAS, Structure, Function and Regulation of Biological Marco-molecule Complexes, Core PI , 2014.1-2018.12 　　
7. Interactional Collaboration and Communication Project, National Natural Science Foundation of China, Protein Structure-based Anti-HIV Drug Discovery, Participant, 2012.1-2012.12 　　
8. Mianshang Project, National Natural Science Foundation of China, Crystal Structural Studies of Complexes between Chemokine Receptor CXCR4 and Peptide Ligands, Project Leader, 2013.1-2016.12 　　
9. Basic Research Project, Shanghai Science and Technology Commission, Structural Studies of Complexes between HIV-1 Co-receptor CXCR4 and Ligands, Project Leader, 2012.1-2014.12 　　
10. Pujiang Talent Program, Shanghai Science and Technology Commission, Structural Studies of G Protein-coupled Receptors, Project Leader, 2013.1-2014.12

Achievements

Prof. WU Beili started her research group at Shanghai Institute of MateriaMedica (SIMM), CAS in July 2011. Within two years, her group established a GPCR structural biology research platform, and successfully solved crystal structures of several GPCRs. The studies were published on Science and Nature. Her research achievements in the recent five years are in details as the following:

1. Structural studies of chemokine receptor CXCR4
Complex structures of CXCR4 bound to small molecule antagonist IT1t and peptide ligand CVX15, respectively, were determined by Prof. Wu in 2010.The results was published on Science in November 2011 [Science, 2010, 330: 1066 (Beili Wu as the first author)]

2. Structural studies of chemokine receptor CCR5
After the structural determination of CXCR4, Dr. Wu continued her effort on structural studies of HIV-1 co-receptors by solving the complex structure of CCR5 bound to an anti-HIV drug maraviroc in 2013. The CCR5 structural study was published on Science in September 2013 [Science, 2013, 341:1387 (Beili Wu as the corresponding author)]

3. Structural studies of purinergic receptor P2Y12R
In 2013, Prof. Wu's group solved complex structures of human purinergic receptor P2Y12R bound to an antagonist and an agonistby collaborating with Dr. Qiang Zhao’s lab at SIMM. The P2Y12R structures were published as two research papers “back to back” on Nature in May 2014 [Nature, 2014, 509: 115-118 and Nature, 2014, 509: 119-122 (Beili Wu as one of the co-corresponding authors)].

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Social Titles

Since 2012, Structural Biology and Molecular Biophysics Committee, Shanghai Society of Biophysics
Since 2014, Molecular Biophysics Committee, the Biophysical Society of China

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Awards & Honors

09/2012, Shanghai Pujiang Talent
05/2014, 2013 May 4th Medal in Shanghai Science and Technology System
06/2014, Chinese Academy of Sciences Shanghai BranchYoung Scholar’s Award

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Pubilcations

Full Publication List

Selected Publications

1. A. Qiao, S. Han, X. Li, Z. Li, P. Zhao, A. Dai, R. Chang, L. Tai, Q. Tan, X. Chu, L. Ma, T. S. Thorsen, S. Reedtz-Runge, D. Yang, M. W. Wang, P. M. Sexton, D. Wootten*, F. Sun*, Q. Zhao*, B. Wu*, Structural basis of Gs and Gi recognition by the human glucagon receptor. Science 367, 1346-1352 (2020).

2. T. Chen, M. Xiong, X. Zong, Y. Ge, H. Zhang, M. Wang, G. Won Han, C. Yi, L. Ma, R. D. Ye, Y. Xu, Q. Zhao*, B. Wu*, Structural basis of ligand binding modes at the human formyl peptide receptor 2. Nat Commun 11, 1208 (2020).

3. H. Fan, S. Chen, X. Yuan, S. Han, H. Zhang, W. Xia, Y. Xu, Q. Zhao*, B. Wu*, Structural basis for ligand recognition of the human thromboxane A2 receptor. Nat Chem Biol 15, 27-33 (2019).

4. S. Chen, M. Lu, D. Liu, L. Yang, C. Yi, L. Ma, H. Zhang, Q. Liu, T. M. Frimurer, M. W. Wang, T. W. Schwartz, R. C. Stevens, B. Wu*, K. Wuthrich*, Q. Zhao*, Human substance P receptor binding mode of the antagonist drug aprepitant by NMR and crystallography. Nat Commun 10, 638 (2019).

5. H. Zhang, A. Qiao, L. Yang, N. Van Eps, K. S. Frederiksen, D. Yang, A. Dai, X. Cai, H. Zhang, C. Yi, C. Cao, L. He, H. Yang, J. Lau, O. P. Ernst, M. A. Hanson, R. C. Stevens, M. W. Wang, S. Reedtz-Runge, H. Jiang, Q. Zhao*, B. Wu*, Structure of the glucagon receptor in complex with a glucagon analogue. Nature 553, 106-110 (2018).

6. Z. Yang, S. Han, M. Keller*, A. Kaiser, B. J. Bender, M. Bosse, K. Burkert, L. M. Kogler, D. Wifling, G. Bernhardt, N. Plank, T. Littmann, P. Schmidt, C. Yi, B. Li, S. Ye, R. Zhang, B. Xu, D. Larhammar, R. C. Stevens, D. Huster, J. Meiler, Q. Zhao, A. G. Beck-Sickinger*, A. Buschauer, B. Wu*, Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor. Nature 556, 520-524 (2018).

7. H. Zhang, A. Qiao, D. Yang, L. Yang, A. Dai, C. de Graaf, S. Reedtz-Runge, V. Dharmarajan, H. Zhang, G. W. Han, T. D. Grant, R. G. Sierra, U. Weierstall, G. Nelson, W. Liu, Y. Wu, L. Ma, X. Cai, G. Lin, X. Wu, Z. Geng, Y. Dong, G. Song, P. R. Griffin, J. Lau, V. Cherezov, H. Yang, M. A. Hanson, R. C. Stevens, Q. Zhao, H. Jiang, M. W. Wang*, B. Wu*, Structure of the full-length glucagon class B G-protein-coupled receptor. Nature 546, 259-264 (2017).

8. G. Song, D. Yang, Y. Wang, C. de Graaf, Q. Zhou, S. Jiang, K. Liu, X. Cai, A. Dai, G. Lin, D. Liu, F. Wu, Y. Wu, S. Zhao, L. Ye, G. W. Han, J. Lau, B. Wu, M. A. Hanson, Z. J. Liu, M. W. Wang*, R. C. Stevens*, Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature 546, 312-315 (2017).

9. T. Hua, K. Vemuri, M. Pu, L. Qu, G. W. Han, Y. Wu, S. Zhao, W. Shui, S. Li, A. Korde, R. B. Laprairie, E. L. Stahl, J. H. Ho, N. Zvonok, H. Zhou, I. Kufareva, B. Wu, Q. Zhao, M. A. Hanson, L. M. Bohn, A. Makriyannis, R. C. Stevens*, Z. J. Liu*, Crystal Structure of the Human Cannabinoid Receptor CB1. Cell 167, 750-762 e714 (2016).

10. D. Zhang, Z. G. Gao, K. Zhang, E. Kiselev, S. Crane, J. Wang, S. Paoletta, C. Yi, L. Ma, W. Zhang, G. W. Han, H. Liu, V. Cherezov, V. Katritch, H. Jiang, R. C. Stevens, K. A. Jacobson, Q. Zhao*, B. Wu*, Two disparate ligand-binding sites in the human P2Y1 receptor. Nature 520, 317-321 (2015).

11. K. Zhang, J. Zhang, Z. G. Gao, D. Zhang, L. Zhu, G. W. Han, S. M. Moss, S. Paoletta, E. Kiselev, W. Lu, G. Fenalti, W. Zhang, C. E. Muller, H. Yang, H. Jiang, V. Cherezov, V. Katritch, K. A. Jacobson, R. C. Stevens, B. Wu*, Q. Zhao*, Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature 509, 115-118 (2014).

12. J. Zhang, K. Zhang, Z. G. Gao, S. Paoletta, D. Zhang, G. W. Han, T. Li, L. Ma, W. Zhang, C. E. Muller, H. Yang, H. Jiang, V. Cherezov, V. Katritch, K. A. Jacobson, R. C. Stevens, B. Wu*, Q. Zhao*, Agonist-bound structure of the human P2Y12 receptor. Nature 509, 119-122 (2014).

13. Q. Tan, Y. Zhu, J. Li, Z. Chen, G. W. Han, I. Kufareva, T. Li, L. Ma, G. Fenalti, J. Li, W. Zhang, X. Xie, H. Yang, H. Jiang, V. Cherezov, H. Liu, R. C. Stevens, Q. Zhao, B. Wu*, Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science 341, 1387-1390 (2013).

14. B. Wu, E. Y. Chien, C. D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F. C. Bi, D. J. Hamel, P. Kuhn, T. M. Handel, V. Cherezov, R. C. Stevens*, Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066-1071 (2010).

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