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张友明

0086-531-88363082 zhangyouming@sdu.edu.cn

教育背景
博士  1990.5.-1994.12.       德国海德堡大学        分子及细胞生物学
硕士  1985.9.-1988.7.    中国医学科学院/协和医大   生化与分子生物学
本科  1981.9.-1985.7.         厦门大学               生物化学
工作经历
2013.4.–现在     山东大学    特聘教授,微生物技术国家重点实验室主任,国家“千人计划”创新人才获得者
2000.7.–2013.2.  德国Gene Bridges GmbH   首席科技官(Chief Scientific Officer)及公司首创者 (Founder)
1998.7.–2000.6.  德国欧洲分子生物学实验室(EMBL),欧洲分子生物学组织 (EMBO)的长期研究员(long-term fellowship)
1997.1.–1998.6.  德国,海德堡,欧洲分子生物学实验室(EMBL)   博士后
1995.1.–1996.12. 德国,海德堡大学医学院                      博士后
1988.9.–1990.4.  中国医学科学院/北京协和医大                  助研
科研方向
1. 继续发展和改良DNA重组工程技术体系:张友明教授作为Red/ET重组工程(Red/ET Recombineering)的首创者,在《Nature Genetics》、《Nature Biotechnology》、《Genes & Development》等发表系列论文,从各个方面阐述了该技术的应用,拥有多项国际专利,奠定了在该领域的领导地位;开发了DNA直接克隆技术,在2012年《Nature Biotechnology》期刊上发表,并申请了国际专利,在微生物新药物的开发中具有广泛应用前景;建立了位点特异性重组技术(例如优化的Cre诱导表达系统等)。此DNA重组工程技术体系已经在世界上多个实验室和生物制药公司得到广泛应用。在这些工作基础上,张友明教授课题组将继续对DNA重组工程进行技术上的改良和机制上的深入阐释,以促进此技术体系得到进一步开发和应用。
2. 利用改良的DNA重组工程技术开展天然活性产物和靶向药物的研究:本课题组建立的DNA重组工程体系用于改良和生产抗肿瘤药物\抗细菌药物的研究以及对趋磁细菌产磁小体的基因簇的克隆、修饰并异质表达的研究已经先后在Nature Biotechnology、Nature Nanotechnology上发表。本实验室将利用改良的此技术体系继续开展抗癌\抗菌\抗衰老\抗胆固醇药物的高效生产、结构改良、生物合成机制的阐释等(Red/ET重组工程发展及应用相关研究工作已经发表论文80余篇(其中有10篇Nature及其系列论文发表)。
3. 利用改良的DNA重组工程技术构建人源化动物模型,开展靶向药物治疗的研究:本课题组将利用自己开发的位点特异性重组的技术平台来构造人源化动物模型,用以生产在人体内不被排斥的和产生免疫反应的人源化抗体药物,研究药物在体内的代谢及抗药机理,并用人源化动物进行临床1期实验,为药物靶向治疗提供理论和实践工具。
4. 应用DNA重组工程技术研究肿瘤靶向送药:许多细菌可以在实体肿瘤里生长但是却不能在人体正常组织里存活,这些细菌甚至可以通过静脉注射,最后只在实体肿瘤里大量增殖,并抑制肿瘤的生长。张友明教授课题组筛选了一批菌株,其中一些本身可以显著抑制肿瘤的生长和转移。同时将表达抗肿瘤药物的PKS/NRPS基因簇通过DNA重组工程技术改造后导入这些在肿瘤里生长的细菌,使其在肿瘤里产生抗肿瘤的药物,实现肿瘤靶向送药,从而达到抑制和消除肿瘤。

主持课题
1. 2016/01−2020/12   微生物基因组工程学科创新引智基地 教育部/国家外专局高等学校学科创新引智计划,B16030,450万
2. 2017 /01-2020 /12    国家自然科学基金面上项目、利用Red/ET DNA重组工程改造蛋白酶体抑制剂syrbactins生物合成途径开发抗肿瘤药物,31670097,60万(张友明主持)
3. 2009-2012, Lipopeptide and secondary metabolites pathway expression with recombineering in Burkholderia und Bacillus, 德国联邦科教部(BMBF),46万欧元
4. 2013-2014,山东大学特聘教授启动基金,300万
5. 2014-2019,山东大学“千人计划”特聘教授基金,1100万
重要论文(2010年 – 2016年)
1. Hu S, Liu Z, Zhang X, Zhang G, Xie Y, Ding X, Mo X, Stewart AF, Fu J*, Zhang Y*, Xia L*. "Cre/loxP plus BAC": a strategy for direct cloning of large DNA fragment and its applications in Photorhabdus luminescens and Agrobacterium tumefaciens. Sci Rep. 2016 Jul 1;6:29087.
2. Wang H, Li Z, Jia R, Hou Y, Yin J, Bian X, Li A, Müller R, Stewart A F, Fu J*, Zhang Y*. RecET direct cloning and Redαβ recombineering of biosynthetic gene clusters, large operons or single genes for heterologous expression. Nature Protocols, 2016/6,11:1175-79
3. Tu Q, Herrmann J, Hu S, Raju R, Bian X, Zhang Y*, Müller R*. Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering. Sci Rep. 2016 Feb 15;6:21066.
4. Yin J, Hoffmann M, Bian X, Tu Q, Yan F, Xia L, Ding X, Stewart AF, Müller R*, Fu J*, Zhang Y*.Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2). Sci Rep. 2015 Oct 13;5:15081.
5. Tang B, Yu Y, Zhang Y*, Zhao G*, Ding X*. Complete genome sequence of the glidobactin producing strain [Polyangium] brachysporum DSM 7029. J Biotechnol. 2015 Sep 20;210:83-84.
6. Bian X, Plaza A, Yan F, Zhang Y*, Müller R*. Rational and efficient site-directed mutagenesis of adenylation domain alters relative yields of luminmide derivatives in vivo. Biotechnol Bioeng. 2015 Jul;112(7):1343-53.
7. Tang Y, Frewert S, Harmrolfs K, Herrmann J, Karmann L, Kazmaier U, Xia L, Zhang Y*, Muller R*. Heterologous expression of an orphan NRPS gene cluster from Paenibacillus larvae in Escherichia coli revealed production of sevadicin. J Biotechnol. 2015 Jan; 20;194:112-4.
8. Yin J, Zhu H, Xia L, Ding X, Hoffmann T, Hoffmann M, Bian X, Müller R, Fu J, Stewart F, and Zhang Y*. A new recombineering system for Photorhabdus and Xenorhabdus. Nucleic Acids Res. 2015 Mar 31;43(6):e3.  
9. Bian X, Plaza A, Zhang Y*, Müller R*. Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety. Chem Sci. 2015, 6(5): 3154−60.
10. Bian X, Huang F, Wang H, Klefisch T, Müller R* and Zhang Y*. Heterologous production of glidobactins/luminmycins in Escherichia coli nissle containing the glidobactin biosynthetic gene cluster from burkholderia DSM7029. ChembioChem. 2014 Oct 13;15(15):2221-4.
11. Bian X, Huang F, Wang H, Klefisch T, Müller R* & Zhang Y*. Heterologous production of glidobactins/luminmycins in Escherichia coli Nissle containing the glidobactin biosynthetic gene cluster from Burkholderia DSM7029. Chembiochem. 2014, doi: 10.1002/cbic.201402199 (SCI, 5-year IF: 3.3) 
12. Kolinko I, Lohße A, Borg S, Raschdorf O, Jogler C, Tu Q, Pósfai M, Tompa E, Plitzko JM, Brachmann A, Wanner G, Müller R, Zhang Y* & Schüler D*. Biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene transfer. Nat Nanotechnol. 2014, 9(3):193-197 (SCI, 5-year IF: 38.6).
13. Wang H, Bian X, Xia L, Ding X, Müller R, Zhang Y*, Fu J* & Stewart AF*. Improved seamless mutagenesis by recombineering using ccdB for counterselection. Nucleic Acids Res. 2013, 42(5):e37(SCI, 5-year IF: 8.4, 2013 IF: 8.8).
14. Hu S, Fu J, Huang F, Ding X, Stewart AF, Xia L*, & Zhang Y*. Genome engineering of Agrobacterium tumefaciens using the lambda Red recombination system. Appl Microbiol Biotechnol. 2014, 98(5):2165-2172 (SCI, 5-year IF: 3.8).
15. Ongley SE, Bian X, Zhang Y, Chau R, Gerwick WH, Müller R & Neilan BA*. High titer heterologous production of lyngbyatoxin in E. coli, a protein kinase C activator from an uncultured marine cyanobacterium. ACS Chem Biol. 2013, 8(9):1888-1893 (SCI, 5-year IF: 5.6).
16. Bian X, Fu J, Plaza A, Herrmann J, Pistorius D, Lou H, Stewart F A, Zhang Y* & Müller, R*. In vivo evidence for a prodrug activation mechanism during colibactin maturation. ChemBioChem. 2013, 14(10):1194-1197(SCI, 5-year IF: 3.3).
17. Bian X, Plaza A, Zhang Y* & Muller R*. Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli. J Nat Prod. 2012, 75(9):1652-1655. (此文被美国生药学会选为2012年度最佳论文) (SCI, 5-year IF: 3.3, 2013 IF: 3.9)
18. Bian X, Huang F, Stewart F A, Xia L, Zhang Y* & Müller R*. Direct cloning, genetic engineering, and heterologous expression of the syringolin biosynthetic gene cluster in E. coli through Red/ET recombineering. ChemBioChem. 2012, 13 (13): 1946-1952 (SCI, 5-year IF: 3.3).
19. Fu J, Bian X, Hu S, Wang H, Huang F, Seibert P M, Plaza A, Xia L, Müller R, Stewart F A & Zhang Y*. Enhanced direct DNA cloning by full length RecE and its application to bioprospecting for secondary metabolites. Nat Biotechnol. 2012. 30(5):440-446 (SCI, 5-year IF: 35.6, 2013 IF 39.08).
20. Bird AW, Erler A, Fu J, Hériché JK, Maresca M, Zhang Y, Hyman AA* & Stewart AF*. High-efficiency counterselection recombineering for site-directed mutagenesis in bacterial artificial chromosomes. Nat Methods. 2011, 9(1):103-109 (SCI, 5-year IF: 27.2).

专利(以下均为国际专利)
1. Bian X, Müller R, Fu J, Stewart F A, Zips D and Zhang Y, Heterologous expression of PKS/NRPS gene cluster and targeted anticancer drug delivery. (2010), International patent application No: PCT/IB2010/055923
2. Stewart AF, Fu J, and Zhang Y, Method of nucleic acid recombination. (2009), International patent application No: PCT/IB2009/000780
3. Zhang Y, Müller R, Stewart AF, Wenzel S, Gross F and Fu J. Methods for heterologous expression of secondary metabolites. (2005) International patent application No: PCT/IB2005/003650,.issued in UK on August, 2008
4. Stewart AF, Zhang Y and Buchholz F. Novel DNA cloning method. (1997) US patent No. 6,509,156, issued on January 21, 2003. European patent No. 1291420, issued on March 12, 2003.
5. Stewart AF, Zhang Y and Muyrers JPP. Methods and compositions for directed cloning and subcloning using homologous recombination. (1999) United States Patent No. 6,355,412 , issued on 12th of March, 2002
6. Zhang Y, Stewart AF and Muijrers JP.P.. Improved RecT or RecET cloning and subcloning method. (2001) European Patent Application No. 01 117 529.6
7. Stewart AF, Zhang Y and Muyrers JPP. Recombination method. (2001) European Patent Application No. 0103276.2
8. Stewart AF, Zhang Y and Hallet B. Use of a tyrosine recombinase for genetic engineering. (2000). International patent application number: PCT/EP02/07176. Issued in 2005.
9. Nawroth P, Nakagawa K and Zhang Y. Tissue factor for influencing blood vessel formation. (1997). U.S. Patent 6,930,094, Issued on 16th of August, 2005.

 

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