张文华
个人简历
科研成果
教学情况
研究方向
荣誉奖励
论文专著
其他信息
个人简历
基本信息
职称:教授
办公室地址:兰州大学天演楼207
联系电话:18919877920
邮箱:zwh@lzu.edu.cn
专业特长
• 分子生物学、生物化学、生物物理学、结构生物学
• 生物大分子三维结构解析 (X-ray Crystallography、Cryo-EM and SAXS)、大分子结构与功能关系分析、酶-底物识别分子机制和酶催化调控机理、转运核糖核酸(transfer RNA)的转录后修饰的分子机制、细胞作用及生理功能。
学习经历
• 2011年01月―2014年12月 Université de Paris 11,结构生物学,博士研究生
• 2008年09月―2010年12月 兰州大学/中科院生物物理所,生物物理学,硕士研究生
• 2003年09月―2008年07月 山东理工大学,生物工程,大学本科
工作经历
• 2023年08月至今 兰州大学,生命科学学院,“萃英学者”特聘教授
• 2018年03月至今 兰州大学,生命科学学院,生物物理学教授
• 2015年01月―2018年03月 法国国家科学研究中心,博士后研究员
社会服务
• 任兰州大学生命科学学院学位评定委员会委员
• 任中国生物化学与分子生物学会核糖核酸专业分会第十届委员会委员
• 任中国生物化学与分子生物学会基因专业分会第十三届委员会委员
• 任中国生物物理学会RNA治疗学分会第一届委员会委员
• 任中国生物物理学会分子生物物理分会第十二届委员会委员
• 任甘肃省直属机关青年联合会第三届委员会委员(科学技术界)
• 任兰州大学党外知识分子联谊会常务理事
• 任兰州大学2021级生物萃英班(“国家基础学科拔尖学生培养计划”项目)学业导师
学术服务
• 《Advanced Biotechnology》期刊青年编委(A Springer Nature partner journal)
• 《The Innovation》期刊青年编委(A Cell Press partner journal)
科研成果
- 中央高校优秀青年教师科研创新基金(2023―2024),主持
- 细胞活动与逆境适应教育部重点实验室开放课题基金(2023),主持
- 甘肃省杰出青年项目(2023―2026),主持
- 甘肃省创新群体项目(2023―2026),参与
- 细胞活动与逆境适应教育部重点实验室开放课题基金(2021),主持
- 中央高校优秀青年教师科研创新基金(2021―2022),主持
- 中央高校基本科研业务费学科交叉创新团队(2021―2023),参与
- 国家自然科学基金青年项目(2021―2023),主持
- 甘肃省自然科学基金面上项目(2021―2022),主持
- 中央高校优秀青年教师科研创新基金(2019―2020),主持
- 姚高民生命科学基金(2018―2019),主持
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兰州大学人才引进基金(2018―2020),主持
教学情况
本科生课程教学
生命科学学院《生物化学》
萃英学院《合成生物学》
药学院《生物化学与分子生物学》(2019―2023)(课程负责人)
生命科学学院《生物物理学》(合讲)、《结构生物学》(合讲)
研究生课程教学
《Practical Introduction to Structural Study of Macromolecules》(课程负责人)
《结构生物学导论》(合讲)
《天然产物生物合成概论》(合讲)
《生命科学与技术专题》(合讲)
研究方向
Our laboratory is dedicated to studying the biosynthesis and cellular roles of tRNA modifications, with a focal point on tRNA N6-threonylcarbamoyladenosine (t6A), which is a universal and necessary post-transcriptional modification uniquely found at position 37 of ANN–decoding tRNAs in the three domains of life. In some organisms, t6A is further converted to a variety of hypermodified derivatives that include ht6A, m6t6A, ms2t6A, ct6A and ms2ct6A. Here, t6A modification and hypermodifications are dubbed as "t6A family". t6A family modifications energetically and dynamically fine-tune the interactions of the anticodon stem loop of tRNAs with mRNA codons in the ribosomal decoding site and promotes the translational fidelity. The lack of t6A family-modified tRNAs gravely affects cellular proteostasis, causes death of unicellular organisms, interferes with the growing and development of higher eukaryotes, and is also implicated in several human diseases, i.e. neurological disorders and mitochondrial encephalomyopathy.
However, the molecular mechanisms and machinery workings of tRNA t6A-modifying enzymes are still largely unknown, hindering deep dissections of the physiological roles and pathological implications of tRNA t6A family. Over the past decade, we have aggregated ample knowledge and sophisticated techniques in dissecting the structure–function relationship of tRNA t6A family biosynthetic enzymes in Bacteria, Archaea and Eukarya. Though challenging, our laboratory is doggedly elucidating molecular mechanisms and cellular roles of tRNA t6A family modifications, using an array of approaches and techniques in molecular biology, enzymology, structural biology, cellular biology and genetics.
Join us!
荣誉奖项
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兰州大学优秀班主任(2021级基础拔尖人才生物萃英班)(2024)
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第八届全国大学生生命科学竞赛甘肃省一等奖、全国二等奖指导教师(2023)
- 兰州大学“萃英学者”特聘教授荣誉称号(2023)
- 甘肃省杰出青年基金获得者(2023)
- 第四届全国核糖核酸(RNA)青年学术会议优秀报告奖(2023)
- 兰州大学2022年本科毕业论文(设计)及临床毕业实习优秀指导教师奖(2023)
- 兰州大学生命科学学院与口腔医学院第三届青年教师联合讲课比赛三等奖(2019)
论文专著
- ❖ Lu, S., Jin, M., Yu, Z. and Zhang, W. (2024) Structure–function analysis of tRNA t6A-catalysis, assembly, and thermostability of Aquifex aeolicus TsaD2B2 tetramer in complex with TsaE. Journal of Biological Chemistry, 300, 107962. ☆ In News: https://lifesc.lzu.edu.cn/info/1192/6494.htm
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❖ Fu, W., Lin, Y., Bai, M., Yao, J., Huang, C., Gao, L., Mi, N., Ma, H., Tian, L., Yue, P., Zhang, Y., Zhang, J., Ren, Y., Ding, L., Dai, L., Leung, J., Yuan, J., Zhang, W. and Meng. W. (2024) Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing. Acta Pharmaceutica Sinica B., 14, 3931–3948.
- ❖ Zheng, X., Su, C., Duan, L., Jin, M., Sun, Y., Zhu, L. and Zhang, W. (2024) Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A. Nucleic Acids Research, 52, 4523–4540. ☆ In News: https://news.lzu.edu.cn/c/202403/109674.html
- ❖ Chen, W., Jin, M. and Zhang, W. (2024) Characterization of human mitochondrial tRNA t6A-modifying enzyme OSGEPL1. Scientia Sinica Vitae (中国科学:生命科学), 54, 706–722.
- ❖ Jin, M., Zhang, Z., Yu, Z., Chen, W., Wang, X., Lei, D. and Zhang, W. (2023) Structure-function analysis of an ancient TsaD–TsaC–SUA5–TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases. Nucleic Acids Research, 51, 8711-8729. ☆ In News: https://news.lzu.edu.cn/c/202307/103208.htm
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❖ Alexander, L. T., Durairaj, J., Kryshtafovych, A., Abriata, L. A., Bayo, Y., Bhabha, G., Breyton, C., Caulton, S. G., Chen, J., Degroux, S., Degroux, S. Ekiert, D. C., Erlandsen, B. S., Freddolino, P. L., Gilzer, D., Greening, C., Grimes, J. M., Grinter, R., Gurusaran, M., Hartmann, M. D., Hitchman, C. J., Keown, J. R., Kropp, A., Kursula, P., Lovering, A. L., Lemaitre, B., Lia, A., Liu, S., Logotheti, M., Lu, S., Markusson, S., Miller, M. D., Minasov, G., Niemann, H. H., Opazo, F., Phillips, G. N., Jr., Davies, O. R., Rommelaere, S., Rosas-Lemus, M., Roversi, P., Satchell, K., Smith, N., Wilson, M. A., Wu, K. L., Xia, X., Xiao, H., Zhang, W., Zhou, Z. H., Fidelis, K., Topf, M., Moult, J. And Schwede, T. (2023) Protein target highlights in CASP15: Analysis of models by structure providers. Proteins, 91, 1571–1599.
- ❖ Sartre, C., Peurois, F., Ley, M., Kryszke, M. H., Zhang, W., Courilleau, D., Fischmeister, R., Ambroise, Y., Zeghouf, M., Cianferani, S., Ferrandez, Y. and Cherfils, J. (2023) Membranes prime the RapGEF EPAC1 to transduce cAMP signaling. Nature Communications, 14(1):4157.
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❖ Wang, J., Gao, J., Guo, T., Huo, X., Zhang, W., Liu, J. and Wang, X. (2023) Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A, A201D and A201E. Angewandte Chemie International Edition, e202213810.
- ❖ Su, C., Jin, M. and Zhang, W. (2022) Conservation and Diversification of tRNA t6A-Modifying Enzymes across the Three Domains of Life. International Journal of Molecular Sciences, 23, (21), 13600.
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❖ Guo, P., Pang, X., Wang, K., Su, P., Pan, Q., Han, G., Shen, Q., Zhao, Z., Zhang, W. and Shu, X. (2022) Nickel-Catalyzed Reductive Csp(3)-Ge Coupling of Alkyl Bromides with Chlorogermanes. Organic Letters, 24, (9), 1802-1806.
- ❖ Wang, J., Zhou, J., Mao, X., Zhou, L., Chen, M., Zhang, W., Wang, E. and Zhou, X. (2022) Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs, Nucleic Acids Research, 50, 2223-2239.
- ❖ Galicia, C., Lhospice, S., Varela, P., Trapani, S., Zhang, W., Navaza, J., Herrou, J., Mignot, T. and Cherfils, J. (2019) MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus. Nature Communications, 10, 5300.
- ❖ Das, S., Malaby, A., Nawrotek, A., Zhang, W., Zeghouf, M., Maslen, S., Skehel, M., Chakravarthy, S., Irving, T., Bilsel, O., Cherfils J. and Lambright, D. (2019) Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes. Structure, 27, 1782–1797.
- ❖ Missoury, S., Plancqueel, S., Gallay, I., Zhang, W., Liger, D., Durand, D., Dammak, R., Collinet, B. and van Tilbeurgh, H. (2018) The crystal structure of the bacterial TsaB/TsaD/TsaE complex responsible for the essential t6A tRNA-modification. Nucleic Acids Research, 46, 5850-5860.
- ❖ Pichard-Kostuch A., Zhang, W., Liger, D., Daugeron, M., Letoquart, J., Gallay, I., Forterre, P., Collinet, B., van Tilbeurgh, H. and Basta, T. (2018) Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal tRNA t6A. RNA, 24, 926-938.
- ❖ Ferrandez, Y., Zhang, W., Peuroi, F., Akendengué, L., Blangy, A., Zeghouf, M. and Cherfils, J. (2017) Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule. Scientific Reports, 7:14409| DOI:10.1038/s41598-017-13619-2|1-13.
- ❖ Zhang, W., Collinet, B., Perrochia, L., Durand, D. and van Tilbeurgh, H. (2015) The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t6A in Escherichia coli. Nucleic Acids Research, 43, 1804-1817.
- ❖ Zhang, W., Collinet, B., Graille, M., Daugeron, M.C., Lazar, N., Libri, D., Durand, D. and van Tilbeurgh, H. (2015) Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex. Nucleic Acids Research, 43, 3358-3372.
- ❖ Perrochia, L., Crozat, E., Hecker, A., Zhang, W., Bareille, J., Collinet, B., van Tilbeurgh, H., Forterre, P. and Basta, T. (2013) In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya. Nucleic Acids Research, 41, 1953-1964.
- ❖ He, J., Shi, J., Xu, X., Zhang, W., Wang, Y., Chen, X., Du, Y., Zhu, N., Zhang, J., Wang, Q. and Yang, J. (2012) STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway. Journal of Biosciences, 37, 243-257.
- ❖ Jiang, P., Xu, X., Chen, Y., Zhang, W., Serradji, N., Yang, J., Dong, C. and Wang, Q. (2010) PMS-1077, a PAF antagonist, induced differentiation of HL-60 cells with its novel activity. Cell Biology International, 34, 1227-1230.
其他信息
- ❖ 第一届RNA治疗学年会⎯RNA治疗学前沿与挑战(2024.11.30―12.03,昆明)组织委员会 ☞ https://meetings.bsc.org.cn/RNAtherapeutics2024/
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❖首届全国分子生物物理学术研讨会(2024.11.10―11.13,杭州)组织委员会 ☞ https://meetings.bsc.org.cn/NCMB-2024/
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❖ 2024生物物理大会⎯生物物理前沿与人类健康(2024.07.25―07.28,兰州)组织委员会 ☞https://www.bsc.org.cn/2024/
- ❖ 第六届全国核糖核酸(RNA)青年学术会议(2024.06.21―06.23,长沙)组织委员会 ☞https://meeting.csbmb.org.cn/2024RNA-Youth/ (☆ In News: https://www.csbmb.org.cn/news/3985.html)
- ❖ 第十二届全国核糖核酸(RNA)学术会议(2023.12.08―12.11,上海)青年论坛召集人 ☞https://www.csbmb.org.cn/rna2023/index.html (☆ In News: https://www.csbmb.org.cn/news/3869.html)
- ❖ 参加兰州大学第二期高层次人才研修班(2023.07.24―07.28,陇南)
- ❖ 参加领航计划-青年科技领军人才国情研修班(2023.07.02―07.07,广州)
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❖ 参加甘肃省无党派代表人士培训班(2023.05.29―06.02,北京)
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❖ 举办第四届全国核糖核酸(RNA)青年学术会议(2023.04.20―04.22,兰州) ☞http://meeting.csbmb.org.cn/RNA2022
☆ In News: https://news.lzu.edu.cn/c/202304/99831.html - ❖ 参加兰州大学第一期高层次人才研修班(2022.07.02―07.03,会宁)
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❖ 参加教育部第一期高校青年教师国情教育研修班(2021.05.30―06.05,上海)