General

Hui Yang

2014-Present Investigator, Institute of Neuroscience, CAS

Email: huiyang@ion.ac.cn




Research Areas

Genome Engineering

CRISPR/Cas9

Disease Model


Education

   
2012 – 2014           Postdoctoral Associate, Laboratory of Dr. Rudolf Jaenisch, Whitehead Institute, MIT, Cambridge, MA, USA                                                                       
2007 – 2012           Ph.D. candidate, Laboratory of Dr. Jinsong Li, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China   
2003 – 2007      B.S., School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China 


Experience

   
Work Experience
   
Teaching Experience
   

Publications

1.Yang, H.*, Wang, H.*, Shivalila, C.S.*, Cheng, A.W., Shi, L., and Jaenisch, R. (2013). One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering. Cell 154, 1370-1379.
2.Cheng, A.W., Wang, H., Yang, H., Shi, L., Katz, Y., Theunissen, T.W., Rangarajan, S., Shivalila, C.S., Dadon, D.B., and Jaenisch, R. (2013). Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell research 23, 1163-1171.
3.Wang, H.*, Yang, H.*, Shivalila, C.S.*, Dawlaty, M.M., Cheng, A.W., Zhang, F., and Jaenisch, R. (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910-918.
4.Yang, H.*, Liu, Z.*, Ma, Y.*, Zhong, C., Yin, Q., Zhou, C., Shi, L., Cai, Y., Zhao, H., Wang, H., et al. (2013). Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes. Cell research 23, 1187-1200.
5.Jiang, J., Lv, W., Ye, X., Wang, L., Zhang, M., Yang, H., Okuka, M., Zhou, C., Zhang, X., Liu, L., et al. (2013). Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. Cell research 23, 92-106.
6.Shi, L.*, Yang, H.*, and Li, J. (2012). Haploid embryonic stem cells: an ideal tool for mammalian genetic analyses. Protein & cell 3, 806-810. (Review)
7.Yang, H.*, Shi, L.*, Wang, B.A.*, Liang, D., Zhong, C., Liu, W., Nie, Y., Liu, J., Zhao, J., Gao, X., et al. (2012). Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells. Cell 149, 605-617.
8.Gu, T.P.*, Guo, F.*, Yang, H.*, Wu, H.P., Xu, G.F., Liu, W., Xie, Z.G., Shi, L., He, X., Jin, S.G., et al. (2011). The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606-610.
9.Jiang, J., Ding, G., Lin, J., Zhang, M., Shi, L., Lv, W., Yang, H., Xiao, H., Pei, G., Li, Y., et al. (2011). Different developmental potential of pluripotent stem cells generated by different reprogramming strategies. Journal of molecular cell biology 3, 197-199.
10.Yang, H.*, Shi, L.*, Chen, C.D., and Li, J. (2011). Mice generated after round spermatid injection into haploid two-cell blastomeres. Cell Res 21, 854-858.
11.Lin, J., Shi, L., Zhang, M., Yang, H., Qin, Y., Zhang, J., Gong, D., Zhang, X., Li, D., and Li, J. (2011). Defects in trophoblast cell lineage account for the impaired in vivo development of cloned embryos generated by somatic nuclear transfer. Cell Stem Cell 8, 371-375.
12.Yang, H., Shi, L., Zhang, S., Ling, J., Jiang, J., and Li, J. (2010). High-efficiency somatic reprogramming induced by intact MII oocytes. Cell Res 20, 1034-1042.


Papers
   
Patents
   

Research Interests

Genetically modified animals represent a crucial tool for understanding gene function in development and disease. In conventional gene-targeting methods to generate mutant animals, mutations are introduced through homologous recombination in embryonic stem (ES) cells. Targeted ES cells injected into wild-type (WT) blastocysts can contribute to the germline of chimeric animals, generating animals containing the targeted gene modification. It is costly and time consuming to produce single-gene knockout animals.

Moreover, in most mammalian species except rodents, no established ES cell lines are available that contribute efficiently to chimeric animals, which greatly limits the genetic studies in many species.

There are three potential alternative methods to generate gene-targeted animals in other species.

Approach I: Directly injecting DNA or mRNA of site-specific nucleases (ZNFs, TALENs, CRISPR/Cas system) into the one-cell embryo to generate DNA double-strand break (DSB) at a specified locus, which could drive both NHEJ-based gene disruption and homology directed repair (HDR)-based precise gene editing. My recent works have already showed we could used CRISPR/Cas system to generate mice carrying mutations in multiple genes and mice carrying reporter and conditional allele in one step. In future,I will focus on CRISPR/Cas system optimization (Specificity, Mosaicism and Efficiency) and genome engineering in large animals by CRISPR/Cas system.

Approach II: Establishing haploid ES cell lines from androgenetic haploid blastocysts, which partially maintain paternal imprints, and can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes. My previous works shown that this procedure could be applied in mouse, and furthermore we could also generated haploid ES cells from Macaca fascicularis monkey parthenotes. In future, I will aim at producing androgenetic ES cells from primate and generate gene-modified primate by injecting these cells into oocytes.

Approach III: Cloning animals by injection of gene targeted nucleus of somatic cells or ES cells into enucleated oocyte to create gene-modified animals. Animals have been cloned in many species, but not in primate. However, NT-ES cells could be generated from cloned embryo from both primate and human. Therefore, I will concentrate on optimizing embryo culture and manipulation system and elucidating reprogramming mechanism to generate first cloned primate, which could be applied in genetically modified primate generation.

In summary, my interest is to apply different genome engineering approaches to generate genetically modified animals, especially primates, for modeling human disease and understanding gene function in development and disease.


Conferences

   

Collaboration

   

Students

现指导学生

姚璇  01  19179  

周昌阳  02  19179  

黄子健  02  19179  

唐骋  01  19179  

黄佳  02  19179  

高妮   02  19179  

贺冰冰  01  19179  

李贺  01  19179  

王兴  01  19179  

Honors & Distinctions