2002 - 2004  Ph.D, University of Science and Technology of China

2005 - 2006  Research Assistant, Institute of Biophysics, Chinese Academy of Sciences

2006 - 2011  Research Fellow, Research Associate, and Senior Research Scientist

                     Memorial Sloan-Kettering Cancer Center, New York

2011 -           Principal Investigator, Institute of Biophysics, Chinese Academy of Sciences

2015 -           Professor of University of Chinese Academy of Science

Wang’s Awards

2018  Beijing Science and Technology Award, second class

2018  Government special allowance

2017  Distinguished Professor of the Yangtze River Scholars Award Program

2017  HHMI international young scholar

2017  Outstanding tutor of Chinese Academy of Science

2016  The 13^th Chinese young women scientist award

2016  Young and middle-aged outstanding talents, Ministry of Science and Technolog

          The 9^th Tanjiazhen Life Science awards(innovation)

2015  Chinese Annual Paper Awards, Cell Press

2015  Outstanding tutor of Chinese Academy of Science

Students’ Awards

2020  Cheng Zhi, Di Ao Scholarship and National master scholarship

2019  You Lilan, National master scholarship

2019  You Lilan, Special Award of Chinese Academy of Science

2018  Li Xueyan, Outstanding Award of director of Chinese Academy of Science

2017  Li Xueyan and Yin Maolu, National master scholarship

2017  Li Jiazhi, Selected to participate in the 68^th Nobel Prize Winners Conference

2017  Li Jiazhi, Selected to participate in the 13^th International Student Forum

2016  Li Jiazhi, Outstanding Award of director of Chinese Academy of Science

2016  Li Jiazhi, National master scholarship

2016  Zhao Hongtu, Outstanding Graduates Award

2016  Chen Peng, Scholarship of University of Chinese Academy of Science

2015  Zhao Hongtu, Special Award of Chinese Academy of Science

2015  Zhao Hongtu, National master scholarship

2015  Zhao Hongtu, Director Paper Award

The main research focus of our group is to understand how small regulatory RNA or DNAmediates prokaryotic defense against invasion by foreign nucleic acids. The main focus of my work is to systematically demonstrate the mechanisms of (1) the CRISPR-Cas system and (2) Argonaut (Ago) protein-mediated RNA/DNA interference.

1. CRISPR-Cas systems

The clustered regularly interspaced short palindromic repeats (CRISPR), together with CRISPR-associated (Cas) proteins form the microbial adaptive immune system that protects against invading phages and plasmids. The CRISPR-Cas system is a RNA-guided immune system found in nearly half of all bacteria studied, as well as in the majority of archaea. Our research in this area includes the molecular mechanism of spacer acquisition, pre-crRNA processing and RNA-guided DNA/RNA cleavage.The overall goal of our studies of the CRISPR-Cas system is to gain important insights into the structural-functional relationship of the processes prokaryotes use to fight invading nucleic acids.

2. Ago protein-mediated DNA interference

RNA interference is a conserved biological response to double-stranded RNA that regulates gene expression. The response is mediated by small interfering RNAs (siRNAs), which guide the sequence-specific degradation of cognate messenger RNAs (mRNAs).Ago protein is a key component in the RNA interference pathway. Recent bioinformatics analyses suggest that prokaryotic Ago plays a number of critical roles in the anti-viral defense system of bacteria. Unlike its eukaryotic counterpart where mRNA interference is mediated by siRNA, several pAgo proteins have been shown to perform either RNA-guided or DNA-guided interference of DNA.Our long-term goals are to structurally characterize and mechanistically define events associated with RNA or DNA interference.

1. Trost CN, Yang J, Garcia B, Hidalgo-Reyes Y, Fung BCM, Wang J, Lu WT, Maxwell KL, Wang Y* and Davidson AR*. An anti-CRISPR that pulls apart a CRISPR-Cas complex. Nature, 2024. 632(8024):375-382.

2. Deng X, Sun W, Li X, Wang J, Cheng Z, Sheng G and Wang Y*. An anti-CRISPR that represses its own transcription while blocking Cas9-target DNA binding. Nature Communications, 2024, 15(1):1806.

3. Sun W, Cheng Z, Wang J, Yang J, Li X, Wang J, Chen M, Yang X, Sheng G, Lou J and Wang Y*. AcrIIC4 inhibits type II-C Cas9 by preventing R-loop formation. PNAS, 2023, 120(31): e2303675120.

4. Li H^#, Wang J^#, Kuan TA, Tang B, Feng L, Wang J, Cheng Z, Sk?enar J, Derbyshire P, Hulin M, Li Y, Zhai Y, Hou Y, Menke FLH, Wang Y* and Ma W*. Pathogen protein modularity enables elaborate mimicry of a host phosphatase. Cell, 2023, 186(15):3196-3207.

5. Sun W*, Zhao X, Wang J, Yang X, Cheng Z, Liu S, Wang J, Sheng G and Wang Y*. Anti-CRISPR AcrIIC5 is a dsDNA mimic that inhibits type II-C Cas9 effectors by blocking PAM recognition. Nucleic Acids Research, 2023, 51(4):1984-1995.

6. 邓谢淑婷, 王久宇, 王艳丽*。针对第2大类CRISPR-Cas系统的acr基因的发现及Acr蛋白多样化的抑制机制。中国科学: 生命科学，2023, 53: 1-19。

7. 王康康，王艳丽*。以CasX为例简述新型CRISPR-Cas系统的基本属性和研究方法。微生物学通报，2021, 48(4): 1227-1238。

8. 陈鹏，孙伟，程志，杨晶，王敏，王久宇，陈慧卿，刘亮*，王艳丽*。Anti-CRISPR蛋白AcrVA2的结构生物学研究。生物化学与生物物理进展, 2021, 48(1):77-87.

9. Huang X, Sun W, Cheng Z, Chen M, Li X, Wang J, Sheng G*, Gong W* and Wang Y*. Structural basis for two metal-ion catalysis of DNA cleavage by Cas12i2. Nature Communications, 2020. 11(1): 5241.

10. Yang J^#, Li J^#, Wang J, Sheng G, Wang M, Zhao H, Yang Y* and Wang Y*. Crystal structure of Cas1 in complex with branched DNA. Science China Life Sciences, 2020, 63(4):516-528.

11. 尤李兰，孙伟，杨晓琪，王艳丽*。诺贝尔化学奖授予CRISPR-Cas9基因编辑研究。生物化学与生物物理进展, 2020, 47(11):1119-1126.

12. Sun W^#, Yang J^#, Cheng Z^#, Amrani N, Liu C, Wang K, Ibraheim R, Edraki A, Huang X, Wang M, Wang J, Liu L, Sheng G, Yang Y, Lou J, Sontheimer Ej* and Wang Y*. Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States. Molecular Cell, 2019, 76(6): 938-952.

13. You L, Ma J, Wang J, Artamonova D, Wang M, Liu L, Xiang H, Severinov K, Zhang X*, Wang Y*. Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference. Cell, 2019, 176, 239-253.

14. Liu L, Yin M, Wang M and Wang Y*. Phage AcrIIA2 DNA Mimicry: Structural Basis of the CRISPR and Anti-CRISPR Arms Race. Molecular Cell, 2019, 73, 611-620.

15. Lei J, Sheng G, Cheung PP, Wang S, Li Y, Gao X, Zhang Y*, Wang Y*, Huang X*. Two symmetric arginine residues play distinct roles in Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage, PNAS, 2019,116: 845-853.

16. Chang L^#, Sheng G^#, Zhang Y^#, Shao S, Wang Y* and Sun Y*. AgoFISH: cost-effective in situ labelling of genomic loci based on DNA-guided dTtAgo protein. Nanoscale Horizons, 2019, 4:918-923.

17. Thavalingam A, Cheng Z, Garcia B, Huang X, Shah M, Sun W, Wang M, Harrington L, Hwang S, Hidalgo-Reyes Y, Sontheimer EJ, Doudna J, Davidson AR, Moraes TF*, Wang Y* and Maxwell KL*. Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2. Nature Communication, 2019, 26;10(1):2806.

18. Song G, Chen H, Sheng G, Wang Y* and Lou J*. Argonaute Facilitates the Lateral Diffusion of the Guide along Its Target and Prevents the Guide from Being Pushed Away by the Ribosome. Bichemistry, 2018, 57(15):2179-2183.

19. Yin M, Wang J, Wang M, Li X, Zhang M, Wu Q* and Wang Y*. Molecular mechanism of directional CTCF recognition of a diverse range of genomic sites. Cell Research, 2017, 27(11):1365-1377.

20. Liu L, Li X, Ma J, Li Z, You L, Wang J, Wang M, Zhang X* and Wang Y*. The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a. Cell, 2017. 170(4):714-726.

21. Sheng G, Gogakos T, Wang J, Zhao H, Serganov A, Juranek S, Tuschl T*, Patel DJ*, Wang Y*. Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes. Nucleic Acids Res., 2017, 45(15):9149-9163.

22. Liu L, Li X, Wang J, Yin M, Chen P, Wang M, Li J, Sheng G and Wang Y*. Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities. Cell, 2017,168:121-134.

23. Liu L, Chen P, Wang M, Li X, Wang J, Yin M and Wang Y*. C2c1-sgRNA Complex Structure Reveals RNA-guided DNA Cleavage Mechanism. Molecular Cell, 2017, 65(2):310-322.

24. Swarts DC, Szczepaniak M, Sheng G, Chandradoss SD, Zhu Y, Timmers EM, Zhang Y, Zhao H, Lou J, Wang Y*, Joo C* and Oost J*. Autonomous Generation and Loading of DNA Guides by Bacterial Argonaute. Molecular Cell, 2017, 65(6):985-998.

25. Wang J^#, Ma J^#, Cheng Z, Meng X, You L, Wang M, Zhang X* and Wang Y*. A CRISPR evolutionary arms race: structural insights into viral anti-CRISPR/Cas responses. Cell Research, 2016, 26:1165-1168.

26. Wang J^#, Li J^#, Zhao H, Sheng G, Wang M, Yin M and Wang Y*. Structural and Mechanistic Basis of PAM-Dependent Spacer Acquisition in CRISPR-Cas System. Cell, 2015, 163: 840-853. 

27. Zhao H, Sheng G, Wang J, Wang M, Bunkoczi G, Gong W, Wei Z* and Wang Y*.  Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli. Nature, 2014, 151: 147-150. 

28. Sheng G^#, Zhao H^#, Wang J, Rao Y, Tian W, Swarts DC, van der Oost J, Patel DJ* and Wang Y*. Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage. PNAS, 2014, 111(2): 652-657.

29. Swarts DC, Jore MM, Westra ER, Zhu Y, Janssen JH, Snijders AP, Wang Y, Patel DJ, Berenguer J, Brouns SJJ* and van der Oost J*. DNA-guided DNA interference by a prokaryotic Argonaute. Nature, 2014,507(7491): 258-261.

30. Rüdel S, Wang Y, Lenobel R, Koörner R, Hsiao HH, Urlaub H, Patel D* and Meister G*. Phosphorylation of human Argonaute proteinsaffects small RNA binding. Nucleic Acids Research, 2011,39(6), 2330-2343.

31. Wang Y^#, Ludwig J^#, Schuberth C, Goldeck M, Schlee M, Li H, Juranek S, Sheng G, Micura R, Tuschl T*, Hartmann G* and Patel DJ*. Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I, Nat Struct Mol Biol., 2010, 17(7): 781-787.

32. Wang Y, Juranek S, Li H, Sheng G, Wardle GS, Tuschl T* and Patel DJ*. Nucleation, propagation and cleavage of target RNAs in argonaute silencing complexes. Nature, 2009, 461(7265): 754-761.

33. Wang Y, Juranek S, Li H, Sheng G, Tuschl T* and Patel DJ*. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature, 2008, 456(7224): 921-926.

34. Wang Y, Sheng G, Juranek S, Tuschl T* and Patel DJ*. Structure of the guide-strand-containing argonaute silencing complex. Nature, 2008, 456(7219): 209-213.

35. Wang Y, Liu L, We Z, Cheng Z, Lin Y and Gong W*. Seeing the Process of Histidine Phosphorylation in Human Bisphosphoglycerate Mutase. J Biol Chem., 2006, 281(51),39642-39648.

36. Wang Y, Wei Z, Liu L, Cheng Z, Lin Y, Ji F and Gong W*. Crystal structure of human B-type phosphoglycerate mutase bound with citrate. Biochemical and Biophysical Research Communications, 2005, 331,1207-1215.

37. Wang Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L and Gong W*. Crystal structure of human bisphosphoglycerate mutase. J Biol Chem., 2004, 279(37), 39132-39138.

(From Yanli Wang, November 21, 2024)