王戈林 

靶向NAD代谢的衰老机制和药物发现研究组

邮箱：gelinwang@sjtu.edu.cn

研究方向

课题组综合运用化学生物学、生物化学、结构生物学、细胞生物学、神经生物学、药物化学等多学科交叉手段，长期致力于衰老相关的NAD代谢及细胞生死的稳态调控研究。具体研究方向主要包括但不限于：1）生理/病理条件下NAD代谢的动态调控；2) 细胞衰老和死亡的分子机制；3）筛选和开发新的抗衰老及相关疾病药物，以这些药物分子为探针揭示疾病的发病机理，并设计和开发相应的治疗策略。

研究组长介绍

王戈林，在武汉大学获得微生物学学士学位和遗传学博士学位，曾在美国德州大学西南医学中心、谷歌创建的Calico生命科学公司、清华大学药学院任职任教。于2025年3月加入上海交通大学基础医学院病理生理系，任课题组长。研究工作聚焦于细胞死亡和衰老生物学机制以及抗神经退行和肿瘤等疾病的药物发现，为相关疾病提供了全新的靶点机制和发展前景良好的候选药物。作为通讯作者或第一作者在Cell, Cell Research, Molecular Cell，Nature Chemical Biology, Angew Chem Int Ed，Nature Communications, Genes & Development, PNAS, Nature等国际知名期刊发表论文。拥有多项专利，部分研究成果已进入转化阶段。曾主持多项国家自然科学基金、国际企业合作项目、美国国立卫生研究院重大项目子项目及其他项目。获美国白血病学会职业发展奖。入选北京市外籍高层次人才资助计划、苏州工业园区科技领军人才。

科研项目

1 2023/07至2026/02 调控NAD代谢的神经保护作用研究，Boehringer Ingelheim，285万，主持

2 2021/04至2024/03 NAD代谢相关的衰老机制研究及健康衰老的药物研发，丰田联合研究基金，250万，主持

3 2020/01至2022/12 NAD代谢在能量匮乏和神经退行过程中的调控机制，国家基金委-重大研究计划_培育项目，68万，主持

4 2019/09至2022/08 生理病理条件下NAD代谢的调控机制研究和应用，北京结构生物学高精尖创新中心竞争性科研经费项目，90万，主持

5 2019/01至2022/12 NAD合成关键酶小分子激活剂的筛选及其作用机制和功能的研究，国家基金委-面上项目，57万，主持

代表性论文 (#第一作者; *通讯作者)

1. Zu,Y.#, Wu, C.#, Li, F.#, Yao, H.#, Xia, Y.#, Zhang, R.#, Li, L., Chen, S., Shi, Q., Xi, S., Pang, H., Liu, M., Wang, L., Terpack, S., Wang, W., Chen, S., Zhang, H., Wang, Y., Yang, M., Huang, S., Zhou, F., Tang, Y., Hu, Z., Fan, S., Tang, Y., Lee,Y. and Wang, G.* (2025). The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress. Molecular Cell 85, 2271–2286.

2. 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 nicotinamide phosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity. Cell Research 32, 570-584.

3. 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.

4. 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.

5. 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.

6. 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. (cover story)

7. 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.

8. 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.

9. Li, F., Wu, C., Wang, G.* (2024). Targeting NAD metabolism for the therapy of age‐related neurodegenerative diseases. Neurosci. Bull. 40(2):218-240. (Invited review)

10. Gu, X., Yao, H., Kwon, I.*, Wang, G.* (2022). Small-molecule activation of NAMPT as a potential neuroprotective strategy, Life Medicine 1, 270–272. (Invited research highlight)

11. Cai, Y.#, Song, W.#, Li, J.#, Jing, Y.#, Liang, C.#, Zhang, L.#, Zhang, X.#, Zhang, W.#, Liu, B.#, An, Y.#, Li, J.#, Tang, B.#, Pei, S.#, Wu, X.#, Liu, Y.#, Zhuang, C.#, Ying Y.#, Dou, X.#, Chen, Y.#, Xiao, F.#, Li, D.#, Yang, R.#, Zhao, Y.#, Wang, Y.#, Wang, L.#, Li, Y.#, Ma, S.*, Wang, S.*, Song, X.*, Ren, J.*, Zhang, L.*, Wang, J.*, Zhang, W.*, Xie, Z.*, Qu, J.*, Wang, J.*, Xiao, Y.*, Tian Y.*, Wang G.*, Hu, P.*, Ye, J.*, Sun, Y.*, Mao, Z*, Kong, Q.*, Liu, Q.*, Zou, W.*, Tian, X.*, Xiao, Z.*, Liu, Y.*, Liu, J.*, Song, M.*, Han, J.* & Liu, G.* (2022). The landscape of aging. Sci China Life Sci 65, 2354–2454.

12. 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. Natl. Acad. Sci. USA. 104, 2068-2073.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Xi, S., Zhang, J. Y., Guo, Z., Zu, Y. M., Liu, Y., Wang, G., Tang, Y. F.* (2022). Facile access to spiro[4,5]decanes through oxidative dearomatizationinduced ring expansion of cyclobutanes. Synthesis 54, 3962-3976.

19. 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. Proc. Natl. Acad. Sci. USA. 109, 17010-17015.

20. 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.

21. 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.

22. 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.

荣誉与奖励

1.2023北京市外籍高层次人才资助计划

2.2023苏州工业园区科技领军人才

3.2023迈阿密冬季研讨会最佳墙报奖

4.2003-2006美国白血病学会职业发展奖

团队介绍

本团队依托细胞分化与凋亡教育部重点实验室与上海交通大学医学院附属第九人民医院共建的"细胞命运决定转化医学研究院"，整合了基础研究与临床医学的双重优势，拥有国际一流的科研平台和交叉创新的学术环境。课题组聚焦衰老机制及干预的前沿科学问题，致力于推动基础研究成果向临床应用的转化，常年招收（聘）硕博生/博士后/助理研究员，诚邀有志于探索生命科学奥秘、具有创新和团队合作精神的青年学者和同学加入。