張永輝研究員對(duì)于膽固醇代謝領(lǐng)域的藥學(xué)研究做出了一些原創(chuàng)性的貢獻(xiàn)。目前（類）膽固醇代謝領(lǐng)域存在三類藥物，一類為他汀藥物，作用于上游的HMG-CoA還原酶；一類為特比萘芬類化合物，作用于真菌的角鯊烯環(huán)氧合酶；還有一類是雙磷酸藥物，靶標(biāo)為法尼基焦磷酸合成酶。除此外，該領(lǐng)域尚無新的靶標(biāo)及對(duì)應(yīng)的藥物出現(xiàn)。張永輝研究員通過對(duì)該生物通路多個(gè)靶點(diǎn)結(jié)構(gòu)、功能及抑制劑的研究，為癌癥治療、非傳統(tǒng)抗細(xì)菌藥物及抗瘧疾藥物的研制提供了很好的研究思路。
（2）與哈佛大學(xué)Timothy Springer教授合作，提出了靶向整合素的藥物研發(fā)新策略，促進(jìn)了Morphic Therapeutic公司的成立；
，開發(fā)了新型的抑制劑，實(shí)現(xiàn)了在小鼠體內(nèi)的瘧原蟲清除，為抗瘧疾藥物的研發(fā)提供了新的靶點(diǎn)；
（5）對(duì)刺激γδ-T細(xì)胞膦抗原的結(jié)構(gòu)與機(jī)制進(jìn)行了研究，糾正了該領(lǐng)域多年關(guān)于膦抗原結(jié)構(gòu)認(rèn)知上的錯(cuò)誤；
Tsinghua-Janssen Investigator Award （2015）
Tsinghua-Janssen Investigator Award (2014)
American Heart Association Fellowship (2006)
Yufeng-Hou Scholarship (1996)
代表性論文
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
