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个人简介

张永辉博士目前为清华大学药学院研究员。 他于1996年在淮海工学院获化学工程学士学位、1999年大连理工大学获应用化学硕士学位,2002年中科院上海有机化学研究所获有机化学博士学位。2002-2003年在晟康公司任部门主管。2003年加入美国伊利诺大学香槟分校化学系博士后,并于2005年获美国心脏协会资助。2008年任化学系高级研究员。2013年入职清华大学医学院药学系(现药学院)研究员。张永辉研究员长期从事(类)胆固醇代谢领域的药学研究工作。迄今张永辉研究员已经发表了50余篇科研论文及多份专利。 荣誉和奖励 Tsinghua-Janssen Investigator Award (2015) Tsinghua-Janssen Investigator Award (2014) American Heart Association Fellowship (2006) Yufeng-Hou Scholarship (1996)

研究领域

张永辉实验室一直致力于胆固醇代谢领域药学新研究方向的开拓、新药物分子的发现及新型疾病治疗方案的探索。具体研究内容包括:(1)针对KRAS突变肿瘤的联合治疗方案;(2)胆固醇代谢通路与免疫调节;(3)新型疫苗佐剂的开发;(4)免疫治疗策略研究;(5)作用于BTN3A1的新型γδ-T细胞膦抗原的发现; (6)改良的γδ-T细胞在肿瘤治疗中的应用;(7)胆固醇代谢中间体的免疫作用机制研究;(8)作用于金黄色葡萄球菌毒力因子的新型抗生素的研制;(9)作用于 PvGGPPS的新型抗疟疾小分子开发。此外,张永辉研究团队还针对IDO1及整合素家族展开了系列药学研究。

近期论文

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Xia, Y., Xie, Y., Yu, Z., Xiao, H., Jiang, G., Zhou, X., Yang, Y., Li, X., Zhao, M., Li, L., Zheng, M., Han, S., Zong, Z., Meng, X., Deng, H., Ye, H., Fa, Y., Wu, H., Oldfield, E., Hu, X., Liu, W*., Shi, Y*., Zhang, Y*. The mevalonate pathway is a druggable target for vaccine adjuvant discovery. Cell , 2018, 175, 1059-1073. Yang, Y., Li, L., Zhou, X., Duan, J., Liu, W., Chen, C., Wang, L., Li, X., Cai, N., Yuan, L., Chen, J., Kang, N., Malwal, S.R., Shi, Y., Oldfield, E*., Guo, R-T*., Zhang, Y*. A structural change in butyrophilin upon phosphoantigen binding underlies phosphoantigen-mediated Vγ9Vδ 2 T cell activation. Immunity, 2019 , 50, 1043-1053. Cai, N., Han, S., Zhang, Y*. Docking complete: a step further toward the holy grail of γδ T cell biology. Immunity, 2019, 51, 781-783. Han, S., Li, X., Xia, Y., Yu, Z., Cai, N., Malwal, S., Han, X., E. Oldfield*., Zhang, Y*. Farnesyl pyrophosphate synthase as a target for drug development: discovery of natural-product-derived inhibitors and their activity in pancreatic cancer cells. J. Med. Chem. 2019, 62, 10867-10896. Malwal, S.R., Gao, J., Hu, X., Yang, Y., Liu, W., Huang, J., Ko, T-Z., Li, L., Chen, C., O’Dowd, B., Khade, R., Zhang, Y., Zhang, Y*., Oldfield, E*., Guo, R-T*. Catalytic role of conserved asparagine, glutatmine, serine, and tyrosine residues in isoprenoid biosynthesis enzymes. ACS Catalysis. 2018, 8, 4299-4312. Wang, Y., Chen, C-C., Yang, Y., Liu, W., Ko, T-P., Shang, N., Hu, X., Xie, Y., Huang, J-W., Zhang,Y*., Guo, R*. Structural insight into a novel indole prenyltransferase in hapalindole-type alkaloid biosynthesis. Biochem. Biphys. Res. Commun . 2018, 495, 1782-1788. Chen, C-C., Hu, X., Tang, X., Yang, Y., Ko, T-Z., Gao, J., Zheng, Y., Huang, J., Yu, Z., Li, L., Han, S., Cai, N., Zhang, Y*., Liu, W*., Guo, R-T*. Crystal structure of a new class of cyclases which catalyze Cope rearrangement. Angew. Chem. Int. Ed. 2018, 57, 15060-15064. Zhou, X., Gu, Y., Xiao, H., Kang, N., Xie, Y., Zhang, G., Shi, Y., Hu, X., Oldfield, E., Zhang, X*., Zhang, Y*. Combining Vγ9Vδ2 T cells with a lipophilic bisphosphonate efficiently kills activated hepatic stellate cells. Front. Immunol. 2017, 8, 1381. Xia, Y., Liu, Y-L., Xie, Y., Zhu, W., Guerra, F., Shen, S., Yeddula, N., Fischer, W., Low, W., Zhou, X., Zhang, Y*., Oldfield, E*., Verma, I. M*. A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin. Sci. Trans. Med. 2014,263ra261.

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