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  杭海英 博士 研究员 博士生导师 

  中科院“百人计划”获得者

  中科院生物物理所,蛋白质与多肽药物所重点实验室,创新课题组组长

  研究方向:基因组稳定性和蛋白质人工进化两个方向的研究

  电子邮件(E-mail ) hh91@sun5.ibp.ac.cn

  电话(Tel) 010-64888473

  传真(Fax) 010-64871293

  邮政编码 100101

  个人网站 

  英文版个人网页

  简历 & 研究组工作摘要  

  1983-1986,中国科学院动物研究所硕士研究生

  1988-1994,美国科罗拉多州立大学博士研究生

  2000-2004,美国哥伦比亚大学助理教授,肿瘤发生

  2004年至今生物物理所研究员

  本实验室从事两个方向的研究:(1)蛋白质人工进化;(2)基因组稳定性。   

       本实验室第一个研究方向是采用体外高速人工进化的方法生成新的有治疗或别的应用价值的新型蛋白质。这些新型蛋白质也可以是新的合成生命系统的元件。这是新兴的合成生物学的一个重要研究领域。我们已成功建成了居于细菌和人细胞两个高速蛋白质人工进化平台。并采用人细胞高速蛋白质人工进化平台成功改造治疗抗体,并提高治疗活性十多倍。我们还成功优化了可检测环境污染的重金属镉的生物探测器。我们正在利用这两个技术平台构建新的蛋白质药物和蛋白质元件。

       从最低等生物到人类,细胞内及其环境因素无时无刻都在对基因组DNA造成损伤。这些损伤威胁生命的延续,或造成机体过早衰老和肿瘤等疾病。细胞通过细胞周期调控、DNA损伤修复、细胞凋亡和细胞衰老等途径的协调配合来修复DNA损伤,维持基因组稳定性。Hus1, Rad1及Rad9是一组在进化上(从酵母到人)保守的细胞周期调控和DNA损伤修复基因。这些基因的突变使细胞对遗传变性剂和环境污染物高度敏感。Hus1, Rad1及Rad9蛋白质形成环状三聚复合体,可套在DNA双链上滑动。我们采用条件基因敲除,证明Rad9和Rad1具有抑癌功能。我们的研究还发现这些蛋白质在DNA修复和细胞周期调控中发挥重要作用。我们目前正在研究这组蛋白质在细胞周期调控、DNA修复和抑制肿瘤发生中的分子机理。 

  发表的论文论著

  2018 

  Chen C, Wang J, Zhao Y, Chen SP, Hu ZS, Chen L*, Hang HY*. Enhancers improve the AID induced hypermutation in episomal vector for antibody affinity maturation in mammalian cell display. Antibodies. 2018(accepted) 

  Fan YJ, Liu YH, Wang YL, Kong BJ, Zhao Y, Ye C, An LL*, Hang HY*. Interaction of the checkpoint protein Rad9 and the non-homologous end-joining protein Ku70. Progress in Biochemistry and Biophysics. 2018, 45(10):1054-1067. 

  Hu ZS, Ye C, Mi W, Zhao Y, Quan C, Li WW*, Li HM*, Hang HY*. Light-scattering detection within the difficult size range of protein particle measurement using flow cytometry. Nanoscale. 2018 Nov 7;10(41):19277-19285. 

  Kong BJ, Cao Y, Wu DN, An LL, Ran FL, Lin Y, Ye C, Wang HL*, Hang HY*. Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones. Applied Microbiology and Biotechnology. 2018 Aug;102(15):6409-6424.

  2016 

  Sun S, Yang X, Wang H, Zhao Y, Lin Y, Ye C, Fang X, Hang H*. Antibody affinity maturation through combining display of two-chain paired antibody and precision flow cytometric sorting. Appl Microbiol Biotechnol. 2016 Jul;100(13):5977-88. 

  Chen C, Li N, Zhao Y*, Hang H*. Coupling Recombinase-mediated cassette exchange with somatic hypermutation for antibody affinity maturation in CHO cells. Biotechnology & Bioengineering. 2016 Jan;113(1):39-51. 

  2015 

  Zhao Y, Ma X, Wang J, Chen S, Yuan H, Xu A, Hang H*, Wu L. The Roles of p21(Waf1/CIP1) and Hus1 in Generation and Transmission of Damage Signals Stimulated by Low-Dose Alpha-Particle Irradiation. Radiat Res. 2015 Dec;184(6):578-85. 

  Li N, An L, Hang H*. Increased Sensitivity of DNA Damage Response-Deficient Cells to Stimulated Microgravity-Induced DNA Lesions. PLOS ONE. 2015, 10(4):e0125236. 

  Zhang Z, Cai Z, Li K, Fang Y, An L, Hu Z*, Wang S*, Hang H*. The Effect of lonizing Radiation on mRNA Levels of the DNA Damage Response Genes Rad9, Rad1 and Hus1 in Various Mouse Tissues. Radiation Research. 2015,183:94-104.    

  2014年   

  刘春春,赵云,杭海英. 流式细胞术揭示出枯草芽孢杆菌多态异质性. 生物化学与生物物理进展. 2014,41(4):393-402.   

  Yue H, Zhao Y, Hang H*. Improvement of engineered microbial production of alkanes through a dual-reporter screening system. 生物物理学报. 2014,30(6):424-432.    

  2013年   

  Yang X, Sun S, Wang HF, Hang H*. Comparison of autotransporter and ice nucleation protein as carrier proteins for antibody display on the cell surface of Escherichia coli. Prog Biochem Biophys. 2013,40(12):1209-1219.   

  Li T, Wang Z, Zhao Y, He W, An L, Liu S, Liu Y, Wang H, Hang H*. Checkpoint protein Rad9 plays an important role in nucleotide excision repair. DNA Repair. 2013 Apr 1;12(4):284-92.   

  2012年   

  Chen S , Qiu J, Chen C, Liu C, Liu Y, An L, Jia J, Tang J, Wu L, Hang H*. Affinity maturation of anti-TNF-α scFv with somatic hypermutation in non-B cells. Protein and Cell. 2012 Jun;3(6):460-9.   

  Zhao Y, He W, Liu WF, Liu CC, Feng LK, Sun L, Yan YB, Hang HY*. Two distinct states of Escherichia coli cells that overexpress the recombinant heterogeneous β-galactosidase. J Biol Chem. 2012 Mar 16;287(12):9259-68.

  2011年   

  Wang Y, An L, Jiang Y, Hang H*. Effects of Simulated Microgravity on Embryonic Stem Cells. PLoS One. 2011;6(12):e29214.   

  Zhang C, Liu Y, Hu Z, An L, He Y, Hang H*. Targeted deletion of mouse Rad1 leads to deficient cellular DNA damage responses. Protein Cell. 2011 May;2(5):410-22.   

  He W, Ma X, Yang X, Zhao Y, Qiu J, Hang H*. A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic Acids Res. 2011 Jun;39(11):4719-27.   

  2010年   

  An L, Wang Y, Liu Y, Yang X, Liu C, Hu Z, He W, Song W and Hang H*. Rad9 is required for B cell proliferation and immunoglobulin class switch recombination. J Biol Chem. 2010 Nov 12;285(46):35267-73.   

  Qiu J, Jung ST, Georgiou G, Hang HY*. Enrichment of Escherichia coli Spheroplasts Displaying scFv Antibodies specific for antigens expressed on the human cell surface. Appl Microbiol Biotechnol. 2010 Dec;88(6):1385-91.   

  Cui P, Lin Q, Xin C, Han L, An L, Wang Y, Hu Z, Ding F, Zhang L, Hu S*, Hang H*, Yu J*. Hydroxyurea-induced Global Transcriptional Suppression in Mouse ES Cells. Carcinogenesis. 2010 31(9):1661-8.

  Han L, Hu Z, Liu Y, Wang X, Hopkins KM, Lieberman HB, Hang H*. Mouse Rad1 deletion enhances susceptibility for skin tumor development. Mol Cancer. 2010 Mar 24;9:67   

  2009年   

  Xu M, Bai L, Gong Y, Xie W, Hang H*, Jiang T. Structure and functional implications of the human rad9-hus1-rad1 cell cycle checkpoint complex. J Biol Chem. 2009 Jul 31;284(31):20457-61.   

  Cui Z, Chen X, Lu B, Park SK, Xu T, Xie Z, Xue P, Hou J, Hang H, Yates JR 3rd, Yang F. Preliminary quantitative profile of differential protein expression between rat L6 myoblasts and myotubes by stable isotope labeling with amino acids in cell culture. Proteomics. 9:1274-92, 2009.

  2008年   

  He W, Zhao Y, Zhang C, An L, Hu Z, Liu Y, Han L, Bi L, Xie Z, Xue P, Yang F, Hang H*. Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1. Nucleic Acids Res. 36:6406-17 (2008).  

  Zhang C, Zhang CX, He Y and Hang H*. Phosphorylation Sites on Tyr28 and the C-terminus of Rad9 are Required for Inhibition of Premature Chromosomal Condensation Across the Entire S Phase. Cell Physiol Biochem, 22:295-306, 2008.   

  Hu Z, Liu Y, Zhang C, Zhao Y, He W, Han L, Yang L, Hopkins KM, Yang X, Lieberman HB, Hang H*. Targeted deletion of Rad9 in mouse skin keratinocytes enhances genotoxin-induced tumor development. Cancer Res. 68:5552-61,2008.   

  Guo Z, Chavez V, Singh P, Finger LD, Hang H, Hegde ML, Shen B. Comprehensive mapping of the C-terminus of flap endonuclease-1 reveals distinct interaction sites for five proteins that represent different DNA replication and repair pathways. J Mol Biol. 377:679-90, 2008.   

  Wang S, Tang M, Pei B, Xiao X, Wang J, Hang H, Wu L. Cadmium-induced germline apoptosis in Caenorhabditis elegans: the roles of HUS1, p53, and MAPK signaling pathways. Toxicol Sci. 102:345-51, 2008.   

  Pei B, Wang S, Guo X, Wang J, Yang G, Hang H, Wu L. Arsenite-induced germline apoptosis through a MAPK-dependent, p53-independent pathway in Caenorhabditis elegans. Chem Res Toxicol. 21:1530-5, 2008   

  Yuan C, Jiao L, Yang L, Ying W, Hu Z, Liu J, Cui F, Li L, Qian L, Teng Y, Hang H, Qian X, Yang X. The up-regulation of 14-3-3 proteins in Smad4 deficient epidermis and hair follicles at catagen. Proteomics. 8:2230-43, 2008.

  2007年   

  Ning Tang, Gangjun Du, Nan Wang, Chunchun Liu, Haiying Hang*, Wei Liang*. Improving Penetration in Tumors with Nano-assemblies of Phospholipids and Doxorubicin. J Natl Cancer Inst. . 2007 Jul 4;99(13):1004-15.   

  2006年   

  刘春春 杭海英*. 生物大分子相互作用检测技术新进展———三色荧光级联荧光共振能量转移技术. 生物化学与生物物理进展. 33:292-296, 2006.   

  苏华 杭海英*. 生理条件下的S期检查点. 生物化学与生物物理进展. 33:122-126, 2006.   

  2004年   

  Hopkins KM, Auerbach W, Wang XY, Hande MP, Hang H, Wolgemuth DJ, Joyner AL, Lieberman HB. Deletion of mouse rad9 causes abnormal cellular responses to DNA damage, genomic instability, and embryonic lethality. Mol Cell Biol. 24:7235-48, 2004.   

  Hopkins KM, Wang X, Berlin A, Hang H, Thaker HM, Lieberman HB. Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue. Cancer Res. 63:5291-8, 2003.   

  Hang H* and Fox MH. Analysis of the mammalian cell cycle by flow cytometry. In Cell Cycle Checkpoint Control Protocols, (Lieberman HB, eds), Humana Press, Totowa, NJ, 2004.   

  2002年   

  Hang H*, Zhang Y, Dunbrack RL, Jr, Wang C, and Lieberman HB. Identification and Characterization of a Paralogue of Human Cell Cycle Checkpoint Gene HUS1. Genomics. 79:487-92, 2002.   

  2000年   

  Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG. PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition. Oncogene. 19:5291-7, 2000.   

  H. Hang, and H.B. Lieberman. Physical interactions among human checkpoint proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression. Genomics 65:24-33, 2000.   

  Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG. Human homologue of S. pombe rad9 interacts with BCL-2/BCL-x L and promotes apoptosis. Nat. Cell Biol. 2:1-6, 2000.   

  H. Hang, Rauth S.J., Hopkins K.M., Lieberman H.B. Mutant alleles of Schizosaccharomyces pombe rad9(+) alter hydroxyurea resistance, radioresistance and checkpoint control. Nucleic Acids Res. 28:4340-9, 2000.   

  1998年   

  H. Hang, S.J. Rauth, K.M. Hopkins, S.K. Davey. and H.B. Lieberman, Molecular cloning and tissue-specific expression of a murine orthologue of the Schizosaccharomyces pombe rad9 checkpoint control gene. J Cell Physiol. 177:241-7, 1998.   

  1996年   

  H. Hang and M.H. Fox. Levels of 70-kDa heat shock protein through the cell cycle in several mammalian cell lines. Cytometry. 25:367-373, 1996.   

  H. Hang, DN. Hager, L. Goriparthi, KM. Hopkins, H. Shih and HB. Lieberman. Schizosaccharomyces pombe rad23 is allelic with swi10, a mating-type switching/ radioresistance gene that shares sequence homology with human and mouse ERCC1. Gene. 170:113-117, 1996.   

  1995年   

  H. Hang, L. He and M.H. Fox. Cell cycle variation of hsp70 levels in HeLa cells at 37o C and after a heat shock. Journal of Cellular Physiology. 165:367-75, 1995.   

  H. Hang, L. He and M.H. Fox. Expression of hsp70 induced in CHO cells by 45.0o C hyperthermia is cell cycle associated and DNA synthesis dependent. Cytometry. 19: 119-125, 1995.   

  1994年以前   

  H. Hang and M.H. Fox. Low pH suppresses synthesis of heat-shock proteins and thermotolerance, Radiation Research. 140:24-30, 1994.   

  E.D. Wieder, H. Hang and M.H. Fox. The measurement of intracellular pH using flow cytometry with carboxy-SNARF-1. Cytometry. 14:1-6, 1993.   

  H. Hang, B. Feng, Z. Zhang. Studies on relationship between Na,K-ATPase activity and sperm capacitation in Guinea pig, Science in China (series B). 33:1304-1310, 1990.   

  * Correspondence author.

  

  资料来源:杭海英研究员,2017-01-01网页更新

                 
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