张昱博士 - 科学研究 - 北京生命科学研究所

张昱博士

北京生命科学研究所研究员

Yu Zhang, Ph.D. Assistant Investigator, NIBS, Beijing，China

Phone：86-10-80727873

Fax： 86-10-80726689

Room Number： B203

E-mail：zhangyu@nibs.ac.cn

教育经历

Education

2004瑞士弗雷德里克-米歇尔研究所博士

Ph.D, Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland

1999北京师范大学生物系硕士

M.S., Department of Biology, Beijing Normal University, Beijing, P.R. China

1996北京师范大学生物系学士

B.S., Department of Biology, Beijing Normal University, Beijing, P.R. China

工作经历

Professional Experience

2013- 北京生命科学研究所研究员

Assistant Investigator, National Institute of Biological Sciences, Beijing, P. R. China

2005-2012 哈佛大学医学院免疫疾病研究所博士后

Postdoctoral Fellow: Immune Disease Institute; Depart of Genetics, Harvard Medical School; Division of Molecular Medicine, The Children’s Hospital, Boston; Boston MA, USA

2004-2005 瑞士弗雷德里克-米歇尔研究所博士后

Postdoctoral Fellow: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland

研究概述

Research Description

染色体的转位是许多血液癌症和实体瘤的特征。研究影响染色体转位发生的机理对研究癌症的起源及对其的预防和治疗提供了重要的启示。我们发现了DNA双链断裂的产生及基因组在细胞核中的空间排列对染色体转位的发生起着决定性的作用。但是, 目前对于导致基因组DNA双链断裂的产生及后续形成染色体转位的其他因素的研究还不是很清楚。同时, 这些可能因子在人类癌症中的作用也需要进一步的研究。我们将要继续利用并完善已经建立的基因组高通量染色体转位测序方法来研究影响染色体转位发生的新因子. 同时我们也将使用其他多种手段, 并利用人类细胞和动物模型研究癌症起始和发展中导致基因组不稳定的分子机制。

Recurrent chromosomal translocations are hallmarks of many hematopoietic cancers and solid tumors. Identification of the mechanistic factors that predispose to chromosomal translocations will provide important insights into cancer etiology as well as the prevention and therapy of cancers. Our previous works have demonstrated that formation of DNA double strand breaks (DSBs) and spatial organization of genome are critical for translocation initiation genome wide. However, much less is known about the mechanisms that lead to genome wide DSBs and subsequent processes that influence the probability of joining pairs of DSBs to form translocations. More importantly how those mechanistic factors contribute to cancer, especially in human patients, has not been carefully studied. We propose to employ and extend our high throughput genomic translocation sequencing (HTGTS) approach to characterize the potential and novel mechanistic factors. In addition, we will employ various genomic approaches to dissect the molecular mechanisms that lead to genomic instability during cancer initiation and development. Finally, we will extend the mechanistic studies to human cells and in vivo animal models.

· Understand how genome wide DSBs predisposed to chromosomal translocations are generated;

· Reveal the causal roles of mechanistic factors in regulating chromosomal translocations;

· Target the end-joining activities which mediate chromosomal translocations;

· Investigate the roles of mechanistic factors in human cancer development.

发表文章

Publications (Now-2013)

1.Hu Q*, Hong Y*, Qi P*, Lu G, Mai X, Xu S, He X, Guo Y, Gao L, Jing Z, Wang J, Cai T, Zhang Y#. Atlas of breast cancer infiltrated B-lymphocytes revealed by paired sigle-cell RNA-sequencing and antigen receptor profiling. Nature Communications. 2021. 12:2186. (*Contributed equally to this work) (#corresponding author) link

2.Xie H, Ge X, Yang F, Wang B, Li S, Duan J, Lv X, Cheng C, Song Z, Liu C, Zhao J, Zhang Y, Wu J, Gao C, Zhang J, Gu F. High-fidelity SaCas9 identified by directional screening in human cells. PLOS Biology. 2020. 18(7): e3000747. link

3.Hua X*, Hu G*, Hu Q*, Chang Y, Hu Y, Gao L, Chen X, Yang P, Zhang Y#, Li M#, Song J#. Single-cell RNA-sequencing for dissecting the immunological network in autoimmune myocarditis. Circulation. 2020. 142:384-400. (*Contributed equally to this work) (#corresponding author) link

4.Han D, Hong Y, Mai X, Hu Q, Lu G, Duan J, Xu J, Si X, Zhang Y #. Systematical study of the mechanistic factors regulating genome dynamics in vivo by CRISPRsie. Journal of Molecular Cell Biology. 2019.074 (#corresponding author) link

5.Pan S, Lin Y, Liu Q, Duan J, Lin Z, Wang Y, Wang X, Lam S, Zou Z, Shui G, Zhang Y, Zhang Z, Zhan X. Convergent genomic signatures of flight loss in birds suggest a switch of main fuel. Nature Communications. 2019.2756 link

6.Duan J*, Lu G*, Hong Y*, Hu Q*, Mai X, Guo J, Si X,Wang F, Zhang Y #.Live imaging and tracking of genome regions in CRISPR/dCas9 knock-in mice.Genome Biology. 2018.19:192(*Contributed equally to this work) (#corresponding author) link

7.Hong Y, Lu G, Duan J, Liu W, Zhang Y #.Comparison and optimization of CRISPR/dCas9/gRNA genome-labeling systems for live cell imaging.Genome Biology. 2018.19(1):39 (*Contributed equally to this work) (#corresponding author) link

8.Li H, Gao S, Huang H,Liu W, Huang H,Liu X, Gao Y, Le R, Kou X, Zhao Y, Kou Z, Li J, Wang H, Zhang Y, Wang H, Cai T,Sun Q,Gao S, Han Z.High throughput sequencing identifies an imprinted gene, Grb10, associated with the pluripotency state in nuclear transfer embryonic stem cells. Oncotarget. 2017.8(29):47344-47355 link

9.Wu W, Lu Z, Li F, Wang W, Qian N, Duan J, Zhang Y, Wang F, Chen T. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model. Proc Natl Acad Sci U S A. 2017.114(7):1660-1665 link

10.Yang H, Zhang W,Lu S,Lu G,Zhang H, Zhuang Y,Wang Y,Dong M, Zhang Y, Zhou X,Wang P, Yu L,Wang F,Chen L. Mup-knockout mice generated through CRISPR/Cas9-mediated deletion for use in urinary protein analysis. Acta Biochim Biophys Sin.2016.48(5):468-473 link

11.Lu G*, Duan J*, Shu S, Wang X, Gao L, Guo J, Zhang Y #. Ligase I and ligase III mediate the DNA double strand break ligation in Alternative End-joining. Proc Natl Acad Sci U S A. 2016. 113(5):1256-1260(*Contributed equally to this work) (#corresponding author) link

12.Dong J, Rohit A, Zhang T, Zhang Y, Hu J, Sabrina A, Robin M, Ho Y, Du Z, Davide F, Meng F, Monica G, Michel C, John P, Frederick W, Alt FW. Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching. Nature. 2015. 525:134–139 link

13.Duan J*, Lu G*, Xie Z, Lou M, Luo J, Guo L, Zhang Y #. Genome-wide identification of CRISPR/Cas9 off-targets in human genome. Cell Res. 2014. Aug;24(8):1009-12. (*Contributed equally to this work) (#corresponding author)link

Publications (2012-1999)

14.Subrahmanyam R, Du H, Ivanova I, Chakraborty T, Ji Y, Zhang Y, Alt FW, Schatz DG, Sen R. Localized epigenetic changes induced by D(H) recombination restricts recombinase to DJ(H) junctions. Nat Immunol. 2012. 13:1205-12 link

15.Zhang Y*, McCord RP*, Ho YJ, Lajoie BR, Dominic HG, Simon AC, Becker MS, Alt FW# and Dekker J#. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell. 2012. 148:908-21 (*Contributed equally to this work) (#corresponding author) link

16.Boboila C, Oksenych V, Gostissa M, Wang JH, Zha S, Zhang Y, Chai H, Lee CS, Mila Jankovic, Albertorio Saez LM, Nussenzweig MC, McKinnon PJ, Alt FW, and Schwer B. Robust Chromosomal DSB Repair Via Alternative End-Joining in the Absence of XRCC1. Proc Natl Acad Sci U S A. 2012. 109:2455-60 link

17.Chiarle R*, Zhang Y*#, Frock RL*, Lewis SM*, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC#, Gostissa M#, Alt FW#. Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. Cell. 2011. 147: 107-19 (*Contributed equally to this work) (#corresponding author) link

18.Zha S, Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann DR, Yuen G, Patel H, Goff PH, Dubois RL, Alt FW. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature. 2011. 469: 250-4link

19.Yamaguchi T, Cubizolles F, Zhang Y, Reichert N, Kohler H, Seiser C, Matthias P. Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. Genes Dev. 2010. 24: 455-69 link

20.Grausenburger R, Bilic I, Boucheron N, Zupkovitz G, El-Housseiny L, Tschismarov R, Zhang Y, Rembold M, Gaisberger M, Hartl A, Epstein MM, Matthias P, Seiser C, Ellmeier W. Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production. J Immunol. 2010. 185: 3489-97 link

21.Brunmeir R, Lagger S, Simboeck E, Sawicka A, Egger G, Hagelkruys A, Zhang Y, Matthias P, Miller WJ, Seiser C. Epigenetic regulation of a murine retrotransposon by a dual histone modification mark. PLoS Genet. 2010. 6: e1000927link

22.Chakraborty T, Perlot T, Subrahmanyam R, Jani A, Goff PH, Zhang Y, Ivanova I, Alt FW, Sen R. A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation. J Exp Med. 2009. 206: 1019-27 link

23.Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol. 2008. 28: 1688-701 link

24.Li G, Alt FW, Cheng HL, Brush JW, Goff PH, Murphy MM, Franco S, Zhang Y, Zha S. Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination. Mol Cell. 2008. 31: 631-40 link

25.Kwon S, Zhang Y, Matthias P. The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev. 2007. 21: 3381-94 link

26.Boyault C*, Zhang Y*, Fritah S*, Caron C, Gilquin B, Kwon SH, Garrido C, YaoTP, Vourc'h C, Matthias P, Khochbin S. HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev. 2007. 21: 2172-81(*Contributed equally to this work) link

27.Zhang Y, Gilquin B, Khochbin S, Matthias P. Two catalytic domains are required for protein deacetylation. J Biol Chem. 2006. 281: 2401-4 link

28.Yan CT, Kaushal D, Murphy M, Zhang Y, Datta A, Chen C, Monroe B, Mostoslavsky G, Coakley K, Gao Y, Mills KD, Fazeli AP, Tepsuporn S, Hall G, Mulligan R, Fox E, Bronson R, De Girolami U, Lee C, Alt FW. XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice. Proc Natl Acad Sci U S A. 2006. 103: 7378-83 link

29.Boyault C, Gilquin B, Zhang Y, Rybin V, Garman E, Meyer-Klaucke W, Matthias P, Muller CW, Khochbin S. HDAC6-p97/VCP controlled polyubiquitin chain turnover. EMBO J. 2006. 25: 3357-66 link

30.Li N, Zhang Y, Naylor MJ, Schatzmann F, Maurer F, Wintermantel T, Schuetz G, Mueller U, Streuli CH, Hynes NE. Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli. EMBO J. 2005. 24: 1942-53 link

31.Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 2003. 22: 1168-79 link

32.He Z, Bai J, Zhang Y. Effect of DNA methylation on protein-DNA interaction of HL-60 cells. Sci China C Life Sci. 1999. 42: 501-5 link

Book:

Zhang Y. Chromosome Translocation. Adv Exp Med Biol. 2018. Vol. 1044.(Eds) link

INVITED REVIEW ARTICLE

1. Zhang Y, Gostissa M, Hildebrand DG, Becker MS, Boboila C, Chiarle R, Lewis S, Alt FW.The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers. Adv Immunol. 2010. 106: 93-133

2. Alt FW#, Zhang Y, Meng F, Guo C, Schwer B. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell. 2013. 152:417-29 (#corresponding author)

Google scholar link:

https://scholar.google.com.hk/citations?hl=en&user=FWuykE4AAAAJ&view_op=list_works&sortby=pubdate