清华大学医学院招聘计算机药物化学博士后1-2名
清华大学医学院教授、青年千人专家张永辉教授招聘：计算机药物化学博士后1-2名联系方法：请将个人简历及代表性论文发至张永辉博士E-mail信箱， yhzhang@biomed.tsinghua.edu.cn;zhangyonghui@tsinghua.edu.cn
PI介绍：张永辉，清华大学医学院药学系教授、博士生导师、中组部青年千人专家。系统开展了多个药物靶标的机理、结构、抑制等研究，开发了多种类的抑制剂并探索了其潜在医用价值。在PNAS、JACS、Angew. Chem、J. Med. Chem、Chem. Biol 、ACS Med. Chem. Lett. 等刊物上发表研究论文近40篇，已获批4份美国专利，另有3份美国专利申请中。双膦酸抗癌药物研制工作、抗疟疾先导药物开发及抗生素研制工作被美联社、《化学与工程新闻》、美国国立卫生研究院（ＮＩＨ）等多次报道。多篇论文入选 Faculty 1000 推荐必读文章。2006年因Chagas疾病方面的研究获American Heart Postdoctoral Fellowship。2013年入选中组部青年千人计划，并入职清华大学医学院药学系任研究员，博士生导师。
张永辉教授主页：
http://www.med.tsinghua.edu.cn/i ... /item/zhang-yonghui
目前研究工作：
（一）萜烯生物合成通道中的重要药物靶酶及对应创新药物研制策略
目前国际市场上共有三类药物作用于萜烯（Isoprenoids）生物合成通道，分别是作用于上游HMG-CoA还原酶的他汀药物，如Lipitor; 作用于中游FPP合成酶的含氮双膦酸抗骨质疏松药物；以及作用于下游角鲨烯环氧化酶的抗真菌药如特比萘芬（兰美抒）。这三类药物每年的市场份额约300亿美金，由此可以窥见该领域新药开发的巨大市场潜力。除了上述三类药物对应的靶标外，在该通道还存在许多潜在的重要药物靶标，但由于基础研究的缺乏、开发技术的限制，对应的药物研制工作进展缓慢。我们将结合有机合成、酶的结构机理研究、计算机辅助设计等手段，系统开展该领域与恶性肿瘤、耐药性病原菌感染相关的原创药物开发工作。
（二）骨、关节相关疾病的药物开发策略
（三）基于结构的热休克蛋白抑制剂的开发及应用
（四）先导化合物发现与优化的技术研究
代表性论文：
1. Zhang, Y*.; Zhu, W.; Liu, Y-L.; Wang, H.; Li, K.; No, J.; Ayong, L,; Gulati, A.; Pang, R.; Morita, C.; Oldfield, E. Chemo-Immunotherapeutic antimalarials targeting isoprenoid biosynthesis. ACS Med. Chem. Lett. 2013, 4， 423-426. (*Corresponding author)
2. Zhu, W1.; Zhang, Y1*.; Sinko, M.; Hensler, M.; Olson, J. et. al. Antibacterial drug leads targeting isoprenoid biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 123-128. (1Contribute equally; *Corresponding author; Featured by Nature Review Drug Discovery, SciBx；Reported by NIH and Science Daily)
3. No, J.H1.; Dossin, F. M1.; Zhang, Y1.; Liu, Y-L.; Ku, M-J.; Zhu, W. et. al. Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium geranylgeranyl diphosphate synthase and exhibit anti-malaria activity. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 4058-4063. (1Contribute equally; Selected by Faculty 1000; Featured by PNAS; Reported by Yahoo and Science Daily)
4. Zhang, Y*.; Lin, F-Y.; Li, K.; Zhu, W.; Liu, Y.L.; Cao, R.; Pang, R.; Lee, E.; Hensler, M.; Wang, K.; Mitchell, D.; Nizet, V.; Oldfield, E. HIV-1 integrase inhibitors inspired antibacterials targeting isoprenoid biosynthesis. ACS Med. Chem. Lett. 2012, 3, 402-406. (*Corresponding author; Featured on the cover and in In This issue).
5. Lin, F1.; Zhang, Y1.; Hensler, M.; Liu, Y.; Chow, O. A.; Zhu, W.; Wang, K.; Pang, R.; Thienphrapa, W.; Nizet, V.; Oldfield, E. Dual dehydrosqualene/squalene synthase inhibitors: Leads for innate immune system based therapeutics. ChemMedChem. 2012, 7, 561-564. (1Contribute equally)
6. Cao, R1.; Zhang, Y1.; Mann, F.M.; Huang, C.; Mukkamala, D.; Hudock, M.P.; Mead, M.E.;Prisic, S.; Oldfield, E. Diterpene cyclases and the nature of the isoprene fold. Proteins. 2010, 78, 2417-32. (1Contribute equally; Featured by Chemical & Engineering News)
7. Singh, A.P.; Zhang, Y, No, J.H.; Docampo, R.; Nussenzweig, V.; Oldfield, E. Lipophilic bisphosphonates are potent inhibitors of Plasmodium liver-stage growth. Antimicrob. Agents Chemother. 2010, 54, 2987-93.
8. Zhang, Y.; Cao R.; Yin, F.; Lin, F.Y.; Wang, H.; Krysiak, K.; No, J.H.; Mukkamala, D.; Houlihan, K.; Li, J.; Morita, C.T.; Oldfield, E. Lipophilic pyridinium bisphosphonates: potent γδT cell stimulators. Angew. Chem. Int. Ed. 2010, 49, 1136-8. (Selected as “hot paper”)
9. Zhang, Y.; Cao, R.; Yin, F.; Hudock, M.P.; Guo, R.T.; Krysiak, K.; et al. Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation. J. Am. Chem. Soc. 2009, 131, 5153-62. (Selected by Faculty 1000; Reported by Reuter，Science Daily; Featured by Chemical & Engineering News)
10. Zhang, Y.; Hudock, M. P.; Krysiak, K.; Cao, R.; Bergan, K.; Yin, F.; Leon, A.; Oldfield, E., Activity of sulfonium bisphosphonates on tumor cell lines. J. Med. Chem. 2007, 50, 6067-79.
11. Chen, C1.; Hudock, M. P1.; Zhang Y1.; Guo, R. T.; Cao, R.; No, J. H.; Liang, P. H.; Ko, T. P.; Chang, T. H.; Chang, S. C.; Song, Y.; Axelson, J.; Kumar, A.; Wang, A. H.; Oldfield, E., Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J. Med. Chem. 2008, 51, 5594-607. (1Contribute equally)
12. Zhang, Y.; Song, Y.; Yin, F.; Broderick, E.; Siegel, K.; Goddard, A.; Nieves, E.; Pasa-Tolic, L.; Tanaka, Y.; Wang, H.; Morita, C. T.; Oldfield, E., Structural studies of Vgamma2Vdelta2 T cell phosphoantigens. Chem. Biol. 2006, 13, 985-92.
13. Xia, Y.; Yeddula, N.; Leblanc, M.; Ke, E.; Zhang, Y.; Oldfield, E.; Verma, I.M. Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat. Cell. Bio. 2012, 14, 257-265.
14. Lin, FY.; Liu, C-I.; Liu, Y-L.; Zhang, Y.; Wang, K.; Jeng, W.Y.; Ko, TP.; Cao, R.; Wang, A.H.; Oldfield, E. Mechanism of action and inhibition of dehydrosqualene synthase.Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 21337-42.
15. Span, I.; Wang, K.; Wang, W.; Zhang, Y.; Bacher, A.; Eisenreich, W.; Li, K.; Schulz, C.; Oldfield, E.; Groll, M. Discovery of acetylene hydratase activity of the iron-sulphur protein IspH. Nat. Comm. 2012, 3, 1042.
16. Wang, K.; Wang, W.; No, J.; Zhang, Y.; Oldfield, E. Inhibition of the Fe4S4 cluster-containing protein IspH (LytB): EPR, metallacycles and mechanisms. J. Am. Chem. Soc. 2012, 132, 6719-6727.
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