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Wei LI, Ph.D., Professor

Genetic engineering, cell/animal models


Staff: Wei LI, Tianda LI, Zhikun LI
Postdoc:Tongtong CUI, Zhengquan HE, Yufei LI, Zhongwen LI, Chao LIU, Yihuan MAO, Chenxin WANG, Leyun WANG, Lei WANG, Libin WANG, Xuewei YUAN
Students: Kaiqiong CHEN, Yangcan CHEN, Moyu DAI, Lin FENG, Zhiqiang HAN, Tiantian JI, Haiping JIANG, Guanyi JIAO, Najmeh Karimi, Chongyang LI, Rongqi LI, Chen LIANG, Bangwei MAO, Youjia SHU, Xuehan SUN, Jing XU, Xiao XU, Ning YANG, Li ZHOU, Liyu ZHU

 

  An old but still unaccomplished goal in biology is to elucidate which and how, genes and their regulations, determine a phenotype/function. Although a series of landmark achievements have emerged in answering this question, it is still very challenging to reconstruct a phenotype/function completely using designed genetic modules. The long-term goal of my research is to understand the genetic basis of certain reproduction- and regeneration-related functions/phenotypes, and to reconstitute such phenotype/function in a given cell or organism for research and therapeutic purposes. Current interests in my laboratory include: (i) developing cutting-edge genome engineering technologies and mammalian synthetic biology. (ii) dissection of genetic and epigenetic basis of reproduction- and regeneration-related phenotypes. (iii) clinical application of gene therapy.



CDetection has high sensitivity and accuracy, and provides an efficient and highly practical platform for DNA detection.



Enhanced targeted indel frequencies by optimized crRNA scaffold. a Schematic showing the workflow of crRNA scaffold optimization and screening. b Efficiencies of GFP disruption in human 293FT cells generated by PrCas12a/scaffold 1 and PrCas12a/scaffold 4n96, respectively. Error bars indicate standard errors of the mean (SEM), n = 3. *p value < 0.05 and **p value < 0.01.



Artificial sgRNAs engineered for genome editing with new Cas12b orthologs

 

Plain English:
Current interests in my laboratory include: (i) developing genome engineering cutting-edge genome engineering technologies and mammalian synthetic biology. (ii) dissection of genetic and epigenetic basis of reproduction- and regeneration-related phenotypes. (iii) clinical application of gene therapy.

 

Selected publications:

 

  1. Guo L#, Sun X#, Wang X#, Liang C#, Jiang H#, Gao Q#, Dai M#, Qu B, Fang S, Mao Y, Chen Y, Feng G, Gu Q, Wang RR*, Zhou Q*, Li W*. SARS-CoV-2 detection with CRISPR diagnostics. (2020) Cell Discov .  6:34. doi: 10.1038/s41421-020-0174-y.
  2. Wang LY#, Li ZK#, Wang LB#, Liu C#, Sun XH, Feng GH, Wang JQ, Li YF, Qiao LY, Nie H, Jiang LY, Sun H, Xie YL, Ma SN, Wan HF, Lu FL*, Li W*, Zhou Q*. Overcoming Intrinsic H3K27me3 Imprinting Barriers Improves Post-implantation Development after Somatic Cell Nuclear Transfer. (2020) Cell Stem Cell  27(2):315-325.e5. doi: 10.1016/j.stem.2020.05.014.
  3. Qu B#, Wu S#, Jiao G#, Zou X#, Li Z#, Guo L#, Sun X, Huang C, Sun Z, Zhang Y, Li H, Zhou Q, Sui R*, Li W*. Treating Bietti crystalline dystrophy in a high-fat diet-exacerbated murine model using gene therapy. (2020) Gene Ther .  27(7-8):370-382.doi: 10.1038/s41434-020-0159-3.
  4. Mao J#, Xu K#, Han J#, Feng G, Zhang Y*, Li W*. Rapid construction of a whole-genome mutant library by combining haploid stem cells and inducible self-inactivating PiggyBac transposon. (2020) Protein Cell . 11(6):452-457. doi: 10.1007/s13238-020-00702-0.
  5. Teng F#, Guo L#, Cui T, Wang XG, Xu K, Gao Q, Zhou Q*, Li W*. CDetection: CRISPR-Cas12b-based DNA detection with sub-attomolar sensitivity and single-base specificity. (2019) Genome Biology  20(1):132. doi: 10.1186/s13059-019-1742-z.
  6. Teng F#, Li J#, Cui T#, Xu K, Guo L, Gao Q, Feng G, Chen C, Han D, Zhou Q*, Li W*. Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds. (2019) Genome Biology  20(1):15. doi: 10.1186/s13059-019-1620-8.
  7. Li Y#, Wang L#, Zhang L#, He Z#, Feng G, Sun H, Wang J, Li Z, Liu C, Han J, Mao J, Li P, Yuan X, Jiang L, Zhang Y, Zhou Q*, Li W*. Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I. (2019) Journal of Cell Bio logy  218(5):1553-1563. doi: 10.1083/jcb.201808088.
  8. Wang J#, Wang L#, Feng G#, Wang Y#, Li Y, Li X, Liu C, Jiao G, Huang C, Shi J, Zhou T, Chen Q, Liu Z, Li W*, Zhou Q*. Asymmetric Expression of LincGET Biases Cell Fate in Two-Cell Mouse Embryos. (2018) Cell  175(7):1887-1901.e18. doi: 10.1016/j.cell.2018.11.039.
  9. Teng F#, Cui T#, Feng G, Guo L, Xu K, Gao Q, Li T, Li J, Zhou Q, Li W*. Repurposing CRISPR-Cas12b for mammalian genome engineering. (2018) Cell Discovery  4:63. doi: 10.1038/s41421-018-0069-3.
  10. Zhang W#, Wan H#, Feng G#, Qu J#, Wang J, Jing Y, Ren R, Liu Z, Zhang L, Chen Z, Wang S, Zhao Y, Wang Z, Yuan Y, Zhou Q, Li W*, Liu G*, Hu B*. SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. (2018) Nature  560(7720):661-665. doi: 10.1038/s41586-018-0437-z.
  11. Li ZK#, Wang LY#, Wang LB#, Feng GH#, Yuan XW#, Liu C, Xu K, Li YH, Wan HF, Zhang Y, Li YF, Li X, Li W*, Zhou Q*, Hu BY*. Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions. (2018) Cell Stem Cell  23(5):665-676.e4. doi: 10.1016/j.stem.2018.09.004.
  12. Xu K#, Yang Y#, Feng GH#, Sun BF#, Chen JQ#, Li YF, Chen YS, Zhang XX, Wang CX, Jiang LY, Liu C, Zhang ZY, Wang XJ, Zhou Q*, Yang YG*, Li W*. Mettl3-mediated m6A regulates spermatogonial differentiation and meiosis initiation. (2017) Cell Research  27(9):1100-1114. doi: 10.1038/cr.2017.100. (Cover story)
  13. Li X#, Cui XL#, Wang JQ#, Wang YK, Li YF, Wang LY, Wan HF, Li TD, Feng GH, Shuai L, Li ZK, Gu Q, Hao J, Wang L, Zhao XY, Liu ZH, Wang XJ, Li W*, Zhou Q*. Generation and application of mouse-rat allodiploid embryonic stem cells. (2016) Cell  164(1-2):279-292. doi: 10.1016/j.cell.2015.11.035.
  14. Wan HF#, Feng CJ#, Teng F#, Yang SH#, Hu BY, Niu YY, Xiang P, Fang WZ, Ji WZ, Li W*, Zhao XY*, Zhou Q*. One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system. (2015) Cell Research  25(2):258-261. doi: 10.1038/cr.2014.158.
  15. Li W#, Li X#, Li TD#, Jiang MG#, Wan HF, Luo GZ, Feng CJ, Cui XL, Teng F, Yuan Y, Zhou Q, Gu Q, Shuai L, Sha JH, Xiao YM, Wang L, Liu ZH, Wang XJ, Zhao XY, Zhou Q*. Genetic modification and screening in rat using haploid embryonic stem cells. (2014) Cell Stem Cell  14(3):404-414. doi: 10.1016/j.stem.2013.11.016.
  16. Li W#, Teng F#, Li T, Zhou Q*. Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. (2013) Nature  Biotechnology  31(8):684-686. doi: 10.1038/nbt.2652.
  17. Li W#, Shuai L#, Wan H#, Dong M#, Wang M, Sang L, Feng C, Luo GZ, Li T, Li X, Wang L, Zheng QY, Sheng C, Wu HJ, Liu Z, Liu L, Wang L, Wang XJ, Zhao XY*, Zhou Q*. Androgenetic haploid embryonic stem cells produce live transgenic mice. (2012) Nature  490(7420):407-411. doi: 10.1038/nature11435.