张永辉研究员对于胆固醇代谢领域的药学研究做出了一些原创性的贡献。目前（类）胆固醇代谢领域存在三类药物，一类为他汀药物，作用于上游的HMG-CoA还原酶；一类为特比萘芬类化合物，作用于真菌的角鲨烯环氧合酶；还有一类是双磷酸药物，靶标为法尼基焦磷酸合成酶。除此外，该领域尚无新的靶标及对应的药物出现。张永辉研究员通过对该生物通路多个靶点结构、功能及抑制剂的研究，为癌症治疗、非传统抗细菌药物及抗疟疾药物的研制提供了很好的研究思路。
（2）与哈佛大学Timothy Springer教授合作，提出了靶向整合素的药物研发新策略，促进了Morphic Therapeutic公司的成立；
Tsinghua-Janssen Investigator Award （2015）
Tsinghua-Janssen Investigator Award (2014)
American Heart Association Fellowship (2006)
Yufeng-Hou Scholarship (1996)
代表性论文
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.
