先后发现多个很有挑战性的小分子化合物的作用机制，使我们对细胞死亡，细胞周期，神经再生等生物学问题有了新的认识。这些小分子也有潜力成为治疗神经退行性疾病或抗肿瘤的药物。谷歌成立的生命科学公司Calico购买了P7C3神经保护分子的专利许可进行药物开发。Diazonamide是全合成化学领域的著名分子，先后被两家生物医药公司进行开发，有望成为疗效好副作用小的肿瘤化疗药物。早期工作系统深入地研究了在动物发育中起重要作用的Hedgehog信号传导的调控机制，也为如何设计药物治疗其信号传导失调所引起的基底细胞癌（皮肤癌中最常见的一种）提供理论基础。

研究成果

1. 首次发现NAD合成的限速酶NAMPT是一类神经保护小分子药物P7C3的靶点, 这些研究使我们认识到提高体内NAD的生物合成可以延缓细胞死亡，有这种效果的小分子药物能发挥抗老年神经退化性疾病的作用，从而帮助相应治疗策略的设计和更优小分子的开发。相关研究成果获得一项专利。

2. 筛选出许多诱发肿瘤细胞死亡的小分子，从中发现了第一个直接通过蛋白多聚化来激活死亡受体DR5的小分子， 这为提供安全的抗癌药物打下基础。

专利和获奖

2022 一种超碳金簇离子型化合物及其制备方法和应用。专利号：CN 113861226B

2020 新型NAMPT酶激动剂及其制备与用途。专利号：202011525254.7，PCT/CN2022/076187

2018 Chemical activators of Nicotinamide Mononucleotide Adenlyly Transferase 2 (NMNAT2) and uses thereof. Patent No.: PCT/CN2018/117723

2017 Neuroprotective compounds and methods for identifying and using same. Patent No.: US 9645139 B2

2009 Ornithine aminotransferase (OAT): a target for anticancer drugs. Patent No.: 7622289 B2 Career Development Award (Special Fellow), Leukemia & Lymphoma Society (2003-2006)

1. Yao, H.#, Liu, M.#, Wang, L.#, Zu, Y.#, Wu, C.#, Li, C., Zhang, R., Lu, H., Li, F., Chen, S., Gu, X., Liu, T., Yang, M., Hua, L., Tang Y.* and Wang, G.* (2022). Discovery of small-molecule activators of nicotinamidephosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity. Cell Research 32, 570-584.

2. Xiao, K.#; Zhang, N.#; Li, F.#; Hou, D.#; Zhai, X.; Xu, W.*; Wang, G.*; Wang, H.*; Zhao, L.* (2022). Pro-oxidant response and accelerated ferroptosis caused by synergetic Au(I) release in hypercarbon-centered gold(I) cluster prodrugs. Nature Communications 13, 4669.

3. Wang, L. B.#; Liu, M. H.#; Zu, Y. M.#; Yao, H.; Wu, C.; Zhang, R. X.; Ma, W. N.; Lu, H. G.; Hua, L.; Wang, G.*; Tang, Y. F.* (2022). Optimization of NAMPT Activators to Achieve in vivo Neuroprotective Efficacy. European Journal of Medicinal Chemistry 236, 114260.

4. Gu, X.; Yao, H.; Kwon, I.*; Wang, G.* (2022). Small-molecule activation of NAMPT as a potential neuroprotective strategy, Life Medicine, https://doi.org/10.1093/lifemedi/lnac012.

5. Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022). The landscape of aging. Sci China Life Sci 65, https://doi.org/10.1007/s11427-022-2161-3

6. Lei, X. Q.; Li, Y. H.; Lai, Y.; Hu, S. K.; Qi, C.; Wang, G.*; Tang, Y. F.* (2021). Strain-Driven Dyotropic Rearrangement: A Unified Ring-Expansion Approach to α-Methylene-γ-butyrolactones. Angew. Chem. Int. Ed. 60, 4221–4230.

7. Wang, X., Zhou, J., Qi, C., Wang, G. (2019). Establishing cell lines overexpressing DR3 to assess the apoptotic response to anti-mitotic therapeutics. J. Vis. Exp. 143, e58705, doi:10.3791/58705.

8. Qi, C., Wang, X., Shen, Z., Chen, S., Yu, H., Williams, N. and Wang, G. (2018). Anti-mitotic chemotherapeutics promote apoptosis through TL1A-activated death receptor 3 in cancer cells. Cell Research 28, 544-555.

9. Wang, G.#, Han, T.#, Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., Mirzaei, H., Pieper, A.A., Ready, J.M. and McKnight, S.L. (2014). P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell 158, 1324-1334.

10. Wang, G.*, Wang, X., Yu, H., Wei, S., Williams, N.S., Holmes, D.L., Halfmann, R., Naidoo, J., Wang, L., Li, L., Chen, S., Harran, P., Lei, X. and Wang. X. (2013). Small-molecule activation of the TRAIL Receptor DR5 in human cancer cells. (*First and co-corresponding author) Nature Chemical Biology 9, 84-89.

Commented by Stu Borman (2013). Small molecule makes cancer want to kill itself: agent is the first small molecule found to trigger death receptor on cancer-cell surfaces. Chemical & Engineering News, 91 (2): 37.

11. Wang, G., Shang, L., Burgett, A.W., Harran, P.G., Wang, X. (2007). Diazonamide toxin reveals a novel function for Ornithine Amino Transferase in mitotic cell division. PROC NAT ACAD SCI (USA) 104, 2068-2073.

12. Jia, J.#, Amanai, K.#, Wang, G.#, Tang, J., Wang, B., Jiang, J. (2002). Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus. Nature 416, 548-552.

13. Wang, G. and Jiang, J. (2004). Multiple Cos2/Ci complexes regulate Ci subcellular localization through microtubule dependent and independent mechanisms. Developmental Biology 268, 493-505.

14. Wang, G., Amanai, K., Wang, B., Jiang, J. (2000). Interactions with Costal2 and suppressor of fused regulate nuclear translocation and activity of Cubitus interruptus. Genes & Development 14, 2893-2905.

15. Wang, G., Wang, B., Jiang, J. (1999). Protein Kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus. Genes & Development 13, 2828-2837.

16. Wang, G.*, Peng, Z., Shen, P. (2000). Cloning and overexpression of the tyrosinase mel gene from Pseudomonas maltophilia. (*First and corresponding author) FEMS Microbiology Letters 185, 23-27.

17. Jesús-Cortés, H.D., Xu, P., Drawbridge, J., Estill, S.J., Huntington, P., Tran, S., Britt, J., Tesla, R., Morlock, L., Naidoo, J., Melito, L.M., Wang, G., Williams, N.S., Ready, J.M., McKnight, S.L., and Pieper, A.A. (2012). Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease. PNAS 109, 17010-17015.

18. Gao, S., Wang, Q., Wang, G., Lomenick, B., Liu, J., Fan, C.W., Deng, L.W., Huang, J., Lum, L., Chen, C. (2012). The chemistry and biology of Nakiterpiosin – C-nor-D-Homos- teroids. Synlett 16, 2298-2310.

19. Zhang, W., Zhao, Y., Tong, C., Wang, G., Wang, B., Jia, J. and Jiang, J. (2005). Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Developmental Cell 8, 267-278.

20. Liu, Y., Wang, G., Zhao, R., Shen, P. and Qu, S. (2005). Microcalorimetric study on the growth of Escherichia coli HB101 effected by recombinant plasmid. ACTACHIMI- CASINICA 63, 327-331.