Small Molecules, Big Effects: Understanding the Action of Nature Products

报告题目：Small Molecules, Big Effects: Understanding the Action of Nature Products

报 告 人：党永军 博士（约翰霍普金斯大学药理和分子科学系）

报告时间： 2011 年11月9日 （星期三）15:00

报告地点：独墅湖校区二期云轩楼1319

欢迎广大师生踊跃参加！

报告内容：

主要是关于天然产物体内分子靶点的鉴定和作用机制的研究。其中深入研究了从海洋生物海绵中分离到的具有抗肿瘤活性的天然产物Pateamine A的靶点鉴定和机理研究。通过生物素标记的Pateamine A,发现它的细胞内靶点是蛋白翻译起始因子eIF 4A 。经过一系列的试验证实它的抗肿瘤活性是通过跟它的靶点相结合而抑制蛋白翻译的起始，进而抑制细胞的生长。以Pateamine A作为分子探针，揭示了新的stress granule形成的机制。该研究提出了以蛋白翻译作为新的药物靶点治疗肿瘤的可能性。

党永军 博士简介

l学习工作简历：

1997年毕业于西北农业大学获学士学位;

2003年毕业于复旦大学遗传所获博士学位;

2004-2009年约翰霍普金斯大学药理和分子科学系博士后;

2010至今约翰霍普金斯大学药理和分子科学系research associate.

l代表性论文：

1.Dang Y,Schneider-Poetsch T, Eyler DE, Jewett JC, Bhat S, Rawal VH, Green R, and Liu JO. (2011) Inhibition of Eukaryotic Translation Elongation by the Antitumor Natural Product Mycalamide B.RNA17(8), 1578-1588(IF=6.051)

2.Dang, Y., Low, W.K., Xu, J., Gehring , N.H. , Dietz, H.C., Romo, D., and Liu, J.O. (2009). Inhibition of nonsense-mediated mRNA decay by the natural product pateamine A through eukaryotic initiation factor 4AIII.J Biol Chem284, 23613-23621. (IF=5.328)

3.Dang, Y., Kedersha, N., Low, W.K., Romo, D., Gorospe, M., Kaufman, R., Anderson, P., and Liu, J.O. (2006). Eukaryotic initiation factor 2alpha-independent pathway of stress granule induction by the natural product pateamine A.J Biol Chem281, 32870-32878. (IF=5.328)

4.Low, W.K*.,Dang, Y*., Schneider-Poetsch, T., Shi, Z., Choi , N.S. , Merrick , W.C., Romo, D., and Liu, J.O. (2005). Inhibition of eukaryotic translation initiation by the marine natural product pateamineA. Mol Cell20, 709-722. (IF=14.194)*co-first author(Featured in the review by Dr. Jon Clardy in ACS Chemical Biology “ Stopping Trouble before It starts” 2005 Vol. 1 No. 1 p17; Highlighted in C & EN News “Protein Synthesis Nipped in the Bud” on December 19, 2005; Commented in “Faculty of 1000” )

5.He, H*.,Dang, Y*., Dai, F., Guo, Z., Wu, J., She, X., Pei , Y., Chen, Y., Ling, W., Wu, C., et al. (2003). Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B.J Biol Chem278, 29278-29287. (IF=5.328) *co-first author

6.Li W,Dang Y,Liu JO, Yu B. (2010). Structural and stereochemical requirements of the spiroketal group of hippuristanol for antiproliferative activity.Bioorg Med Chem Lett. 20(10):3112-5. (IF=2.661)

7.Xu J,Dang Y,Ren YR, Liu JO. (2010). Cholesterol trafficking is required for mTOR activation in endothelial cells.Proc Natl Acad Sci U S A.107(10):4764-9. (IF=9.771)

8.Li, W.,Dang, Y., Liu, J.O., and Yu, B. (2009). Expeditious Synthesis of Hippuristanol and Congeners with Potent Antiproliferative Activities.Chemistry15, 10356-10359. (IF=5.476)

9.Low, W.K.,Dang, Y., Bhat, S., Romo, D., and Liu, J.O. ( 2007a ). Substrate-dependent targeting of eukaryotic translation initiation factor 4A by pateamine A: negation of domain-linker regulation of activity.Chem Biol14, 715-727. (IF=5.838)

10. Low, W.K.,Dang, Y., Schneider-Poetsch, T., Shi, Z., Choi , N.S. , Rzasa, R.M., Shea, H.A., Li, S., Park, K., Ma, G., et al. (2007b). Isolation and identification of eukaryotic initiation factor 4A as a molecular target for the marine natural product Pateamine A.Methods Enzymol431, 303-324. (IF=1.626)

11. Hu, X.,Dang, Y., Tenney, K., Crews, P., Tsai, C.W., Sixt, K.M., Cole, P.A., and Liu, J.O. (2007). Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases.Chem Biol14, 764-774. (IF=5.838)

12. Peddibhotla, S.,Dang, Y., Liu, J.O., and Romo, D. (2007). Simultaneous arming and structure/activity studies of natural products employing O-H insertions: an expedient and versatile strategy for natural products-based chemical genetics.J Am Chem Soc129, 12222-12231. (IF=9.019)(Highlighted in C&EN News “Tagging Natural Products” on Oct. 1, 2007)

13. Wu, J.,Dang, Y.,Su, W., Liu, C., Ma, H., Shan, Y., Pei, Y., Wan, B., Guo, J., and Yu, L. (2006). Molecular cloning and characterization of rat LC 3A and LC3B--two novel markers of autophagosome.Biochem Biophys Res Commun339, 437-442. (IF=2.595)

14. Titov DV, GilmanB, He QL, Bhat S, Low WK,Dang Y, Smeaton M, Demain AJ, Miller PS, Kugel JF, Goodrich JA & Liu JO, (2011) XPB, a subunit of TFIIH, is a target of the natural product triptolide.Nature Chemical Biology7(3):182-8. (IF=15.808) Featured as Cover

15. Chamni S, He QL,Dang Y,Bhat S, Liu JO, and Romo D, (2011) Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O–H Insertion.ACS Chemical Biology(In press)

16. Schneider-Poetsch T, Ju J, Eyler DE,Dang Y,Bhat S, Merrick WC, Green R, Shen B, Liu JO. (2010). Inhibition of Eukaryotic Translation Elongation via the Ribosomal E-site byCycloheximide and Lactimidomycin.Nature Chemical Biology6(3):209-217 (IF=15.808)