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徐彦辉研究组招生启事

发表时间:2011-08-31  |  阅读次数:210次  |  字体大小 [ ]

复旦大学生物医学研究院徐彦辉研究组招收2012年入学的直博或硕博连读研究生,欢迎有免试推荐资格的同学前来咨询。有意者请将简历等个人信息发送至xuyanhui@gmail.com,欢迎有兴趣的同学到实验室参观,或者进行短期实习。

课题组长简介:

徐彦辉    博士/研究员/博士生导师

1995-1999   清华大学生物科学与技术系,1999年获学士学位
1999-2004   清华大学生物科学与技术系,2004年获博士学位
2004.11-2007.12 普林斯顿大学分子生物学系,博士后
2008.1-2008.10 复旦大学生物医学研究院,副研究员
2008.10-今   复旦大学生物医学研究院,研究员,博士生导师

科研项目及奖励:
“浦江人才计划”
新世纪优秀人才支持计划
国家“重大科学研究计划”项目课题负责人
自然科学基金-重点项目,面上项目

研究方向:
我们的研究目标是综合利用结构生物学,生物化学和细胞生物学等手段,深入理解肿瘤发生信号通路中重要蛋白质复合物发挥功能的分子机制和结构基础,并以药物靶标结构为基础,开展药物设计和筛选工作,包括:
1. 肿瘤发生信号转导通路
Hippo signaling pathway是近几年新发现的一个信号通路,通过促进细胞调亡和限制细胞增殖调控器官大小的发育,Hippo信号通路最早在果蝇的遗传学实验中发现,其组分从果蝇到哺乳动物都非常保守。细胞间的接触抑制信号通过上游的一系列级联反应传递到下游,磷酸化并降解癌基因YAP,抑制其转录激活功能。该通路的调控与人类肿瘤的发生密切相关,在多种肿瘤中发现了上游的肿瘤抑制因子的失活和下游的YAP的高表达。本实验室自2008年成立以来一直致力于研究该通路中的蛋白及蛋白复合物结构与功能。已经完成了转录激活复合物YAP-TEAD的研究,阐明了二者结合的重要位点并揭示了YAP通过TEAD发挥功能的分子机制,并找到了依据TEAD表面设计抗肿瘤药物先导化合物的靶点。目前实验室正集中在Hippo信号通路上游的重要复合物的结构和功能研究,以深入理解接触抑制信号从膜外都核内传递的分子机制。
2. 药物先导化合物的设计和筛选
本课题组长期的目标是希望利用基础研究的成果,利用复旦大学药物开发的平台优势,开展基于结构的药物设计与筛选工作。目前,在YAP-TEAD结构的基础上,我们发现TEAD表面存在作为小分子抑制剂作用的结合靶点,可能阻断YAP与TEAD的结合,进而抑制癌基因YAP的促进细胞增殖的活性。我们正在开展针对YAP-TEAD的药物筛选工作,根据得到的三维结构信息,设计和筛选得到阻碍YAP结合的药物先导化合物,有可能成为潜在的抗肿瘤药物。此外,我们还与药学院,肿瘤医院的多位专家合作,针对另外几个靶点开展药物筛选的工作。
3. 染色质组装和修饰的调控机制
表观遗传(epigenetics)修饰及其所调控的染色质结构变化在基因的转录和整个基因组调控中发挥着重要的作用,影响到细胞的生长,分化,胚胎发育,干细胞分化与重编程,与多种疾病的发生密切相关。本实验室致力于利用结构生物学在内的多种手段,对参与染色质组装修饰的蛋白质复合物进行结构和相关的功能研究,以阐明其参与基因转录调控和染色质组装的分子机制。我们最近解析了组蛋白去甲基化酶ceKDM7A与其催化、识别底物的多种复合物结构,阐明了该蛋白识别转录激活信号,去除转录抑制信号的分子机制。

代表论文:

2011
1. Gong, R. *, Li, Li. *, Liu, Y. *, Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K.L. # and Xu, Y. # 2011. Crystal Structure of Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes & development  25 (16): 1668-1673
2. Hu, L. *, Li, Z. *, Wang, P., Lin, Y., and Xu, Y. 2011. Crystal Structure of PHD Domain of UHRF1, Insights into Recognition of unmodified Histone H3 Arginine Residue 2. Cell research (Advanced online on Aug 2nd.)
3. Rajakumara, E., Wang, Z., Ma, H., Hu, L., Chen, H., Lin, Y., Guo, R., Wu, F., Li, H., Lan, F., Shi, Y.G., Xu, Y., Patel, D.J., and Shi, Y. 2011. PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression. Molecular cell 43(2): 275-284.
4. Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.H., Ito, S., Yang, C., Wang, P., Xiao, M.T., Liu, L.X., Jiang, W.Q., Liu, J., Zhang, J.Y., Wang, B., Frye, S., Zhang, Y., Xu, Y.H., Lei, Q.Y., Guan, K.L., Zhao, S.M., and Xiong, Y. 2011. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer cell 19(1): 17-30. (cover story)

2010
5. Yang, Y. *, Hu, L. *, Wang, P. *, Hou, H., Lin, Y., Liu, Y., Li, Z., Gong, R., Feng, X., Zhou, L., Zhang, W., Dong, Y., Yang, H., Lin, H., Wang, Y., Chen, C.D. # and Xu, Y. # 2010. Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell research, 20(8):886-98. (cover story)
6. Lin, H., Wang, Y., Wang, Y., Tian, F., Pu, P., Yu, Y., Mao, H., Yang, Y., Wang, P., Hu, L., Lin, Y., Liu, Y., Xu, Y. # and Chen, C.D. # 2010. Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell research, 20(8):899-907.
7. Yang, H., Wang, Z., Shen, Y., Wang, P., Jia, X., Zhao, L., Zhou, P., Gong, R., Li, Z., Yang, Y., Chen, D. #, Murchie, A. # and Xu, Y. # 2010. Crystal Structure of the Nosiheptide Resistance Methyltransferase of Streptomyces actuosus. Biochemistry, 49(30):6440-50.
8. Li, Z. *, Zhao, B. *, Wang, P., Chen, F., Dong, Z., Yang, H., Guan, K.L. # and Xu, Y. # 2010. Structural insights into the YAP and TEAD complex. Genes & development, 24, 235-240.

Before 2009
9. Xu, Y. *, Chen, Y. *, Zhang, P., Jeffrey, P.D. and Shi, Y. (2008) Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Molecular cell, 31, 873-885.
10. Chen, Y. *, Xu, Y. *, Bao, Q., Xing, Y., Li, Z., Lin, Z., Stock, J.B., Jeffrey, P.D. and Shi, Y. (2007) Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nature structural & molecular biology, 14, 527-534.
11. Xu, Y. *, Xing, Y. *, Chen, Y. *, Chao, Y. *, Lin, Z., Fan, E., Yu, J.W., Strack, S., Jeffrey, P.D. and Shi, Y. (2006) Structure of the protein phosphatase 2A holoenzyme. Cell, 127, 1239-1251.
12. Xing, Y. *, Xu, Y. *, Chen, Y. *, Jeffrey, P.D., Chao, Y., Lin, Z., Li, Z., Strack, S., Stock, J.B. and Shi, Y. (2006) Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins. Cell, 127, 341-353.
13. Xu, Y., Lou, Z., Liu, Y., Pang, H., Tien, P., Gao, G.F. and Rao, Z. (2004) Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. The Journal of biological chemistry, 279, 49414-49419.
14. Xu, Y. *, Liu, Y. *, Lou, Z. *, Qin, L., Li, X., Bai, Z., Pang, H., Tien, P., Gao, G.F. and Rao, Z. (2004) Structural basis for coronavirus-mediated membrane fusion. Crystal structure of mouse hepatitis virus spike protein fusion core. The Journal of biological chemistry, 279, 30514-30522.
15. Xu, Y., Zhu, J., Liu, Y., Lou, Z., Yuan, F., Liu, Y., Cole, D.K., Ni, L., Su, N., Qin, L., Li, X., Bai, Z., Bell, J.I., Pang, H., Tien, P., Gao, G.F. and Rao, Z. (2004) Characterization of the heptad repeat regions, HR1 and HR2, and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome (SARS) coronavirus. Biochemistry, 43, 14064-14071.
16. Xu, Y., Gao, S., Cole, D.K., Zhu, J., Su, N., Wang, H., Gao, G.F. and Rao, Z. (2004) Basis for fusion inhibition by peptides: analysis of the heptad repeat regions of the fusion proteins from Nipah and Hendra viruses, newly emergent zoonotic paramyxoviruses. Biochemical and biophysical research communications, 315, 664-670.
17. Xu, Y., Cole, D.K., Lou, Z., Liu, Y., Qin, L., Li, X., Bai, Z., Yuan, F., Rao, Z. and Gao, G.F. (2004) Construct design, biophysical, and biochemical characterization of the fusion core from mouse hepatitis virus (a coronavirus) spike protein. Protein expression and purification, 38, 116-122.
18. Xu, Y., Su, N., Qin, L., Bai, Z., Gao, G.F. and Rao, Z. (2004) Crystallization and preliminary crystallographic analysis of the heptad-repeat complex of SARS coronavirus spike protein. Acta Crystallogr Sect D, 60, 2377-2379.
19. Xu, Y., Lou, Z., Liu, Y., Cole, D.K., Su, N., Qin, L., Li, X., Bai, Z., Rao, Z. and Gao, G.F. (2004) Crystallization and preliminary crystallographic analysis of the fusion core from two new zoonotic paramyxoviruses, Nipah virus and Hendra virus. Acta Crystallogr Sect D, 60, 1161-1164.
20. Xu, Y., Bai, Z., Qin, L., Li, X., Gao, G. and Rao, Z. (2004) Crystallization and preliminary crystallographic analysis of the fusion core of the spike protein of the murine coronavirus mouse hepatitis virus (MHV). Acta Crystallogr Sect D, 60, 2013-2015.
* These authors contributed equally to the work
# Correspondence

联系方式:
地址:东安路 130号,明道楼 715室,上海 200032
电话:021-54237294 (办公室),021-54237880 (实验室)
传真:021-54237294
邮件:xuyh@fudan.edu.cn or xuyanhui@gmail.com

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