个人简历

罗成博士，中国科学院上海药物研究所/中科中山药物创新研究院研究员，博士生导师，获国家杰出青年基金资助，上海市优秀学科带头人。研究领域：药物设计和化学生物学。罗成发展多学科交叉技术，针对重大疾病相关通路/靶标，开展基于药物化学生物学的靶标新功能发现、药物作用机理研究和创新药物研发。发现了多个重要天然产物或内源代谢物的作用靶标，揭示了多个重要药物靶标的调控机制，三个化合物进入了临床前评价。研究结果在Nature、Science、Cell、Cancer Cell、Nature Chem、Adv Mater、Adv Sci、JACS、PNAS、Nucleic Acid Res和J Med Chem等国际著名杂志发表SCI论文>240篇，H因子45，论文引用8500余次。成果申请专利63项，获得授权专利10余项（部分专利完成转化）；主持“863”课题、基金委重点项目、基金委杰青等项目10余项。已经培养研究生近50名，部分研究生在哈佛大学、芝加哥大学和宾夕法尼亚大学等世界著名高校从事博士后研究，部分在德国海德堡大学等国内外高校获独立PI工作。

研究领域

（1）重大疾病原创靶标的先导化合物发现与作用机制；
（2）重要天然产物的靶标发现、确证和创新药物发现；
（3）基于翻译后修饰的动态调控与化学干预；
（4）重要复合物（体）的动态调控与化学干预。

研究成果

1. 建立多种药物化学生物学实验筛选与确证技术，以包括药物设计、量子化学计算、分子动力学模拟和生物信息学等模拟手段为指导，结合多学科交叉实验确证，获得近20余种重要靶标的先导化合物（6类为该靶标世界首次发现）；获得部分有临床应用前景的化合物，部分已经转化至企业，开展进一步的深度开发研究；
2. 以计算生物学模拟为指导，开展生物化学、结构生物学和药理学实验验证，揭示TET等多个重要靶标蛋白的动态调控与功能的关系，为研究变构调控剂奠定基础；
3. 以计算生物学和组学分析为指导，开展重要天然产物或内源代谢的作用靶标发现，发基于靶标的天然产物药物化学开发和靶标作用机制研究奠定活性物质和潜在靶标基础。

代表性论著（*：通讯作者）

1.Liping Liao, Wenzhen Dang, Tingting Lin, Wen Li, Senhao Xiao, Lei Feng, Jing Huang, Rong Fu, Jiacheng Li, Liping Liu, Mingchen Wang, Hungru Tao, Hualiang Jiang, Kaixian Chen, Bing Zhou*, Xiaoyan Shen*, and Cheng Luo*. A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6. Acta Pharmaceutica Sinica B 2022, in press.

2.Mingming Sun, Leilei Li, Jiaqi Song, Yaya Qiao, Fei Xie, Yingzhi Wang, Huanran Sun, Jiyan Wang, Zhen Li, Sizhen Lai, Hongkai Chang, Han Zhang, Chenxin Yang, Huifang Zhao, Junzhen Tan, Yanping Li, Shuangping Liu, Bin Lu, Min Liu, Guangyao Kong, Yujun Zhao, Chunze Zhang, Cheng Luo*, Changliang Shan*. PRMT6-medaited 6PGD and ENO1 methylation regulates cell metabolism, tumorigenicity, and chemotherapy response of lung cancer. Acta Pharmaceutica Sinica B 2022; in press.

3.Jing Huang, Xiaobo Wang, Shiyu Shen, Ruina Wang, Bing, Li, Hongru Tao, Junchi Hu, Jin Yu,Hualiang Jiang, Kaixian Chen, Cheng Luo*，Yongjun Dang*, Yuanyuan Zhang*, L-5-hydroxytryptophan promotes Antitumor Immunity by Inhibiting PD-L1 Inducible Expression. J ImmunoTherapy of Cancer 2022, in press.

4.Xiaotong Diao, Fei Ye, Meina Zhang, Xintong Ren, Xiaoxu Tian, Jingping Lu, Xiangnan Sun, Zeng Hou, Xiaoyu Chen, Fengwei Li, Jingjing Zhuang, Hong Ding, Chao Peng, Fraydoon Rastinejad*, Cheng Luo*, Dalei Wu*. Identification of oleoylethanolamide as an endogenous ligand candidate for HIF-3α. Nature Communication 2022; in press.

5.Jianhua Mao#, Kongkai Zhu#, Zhangbiao Long#, Huimin Zhang#, Bing Xiao, Wenda Xi, Yun Wang, Jiansong Huang, Jingqiu Liu, Xiaofeng Shi, Hao Jiang, Tian Lu, Yi Wen, Naixia Zhang, Qian Meng, Hu Zhou, Zheng Ruan, Jin Wang, Cheng Luo*, Xiaodong Xi*, Small molecule DCDBS84 regulates platelet  thrombus  formation by targeting c-Src SH3 domain, Adv Sci 2022;e2103228.

6.Shijie Fan, Liyan Yue, Wei Wan, Yuanyuan Zhang, Bidong Zhang, Chinatsu Otomo, Quanfu Li, Pan Xu, Mingrui Zhu, Hongru Tao, Zhifeng Chen, Lianchun Li, Hong Ding, Zhiyi Yao, Junyan Lu, Naixia Zhang, Minjia Tan, Kaixian Chen, Hualiang Jiang, Bin Zhou*, Yongjun Dang*, Takanori Otomo* and Cheng Luo* Inhibition of autophagy by a small molecule through covalent modification of LC3. Angew Chem Int Ed Engl. 2021 Sep 29. doi: 10.1002/anie.202109464.

7.Youyi Zhang, Fei Ye, Tongtong Zhang, Shiyun Lv, Liping Zhou, Fei Guo, Daohai Du, Cheng Luo*, Shujia Zhu* Structural basis of ketamine action on human NMDA receptors. Nature. 2021 Aug;596(7871):301-305.

8.Wang J, Wang C, Xu P, Li X, Lu Y, Jin D, Yin X, Jiang H, Huang J, Xiong H, Ye F, Jin J, Chen Y, Xie Y, Chen Z, Ding H, Zhang H, Liu R, Jiang H, Chen K, Yao Z, Luo C*, Huang Y*, Zhang Y*, Zhang J*. PRMT1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Theranostics. 2021 Mar 12;11(11):5387-5403.

9.Tian Lu, Yong Li, Wenchao Lu, TWGM Spitters, Jun Wang, Simian Cai, Jing Gao,  Yanting Zhou, Zhe Duan, Huan Xiong, Qi Li, Hualiang Jiang, Kaixian Chen, Hu Zhou, Hua Lin, Huijin Feng, Bing Zhou, * Christopher L. Antos, * Cheng Luo*Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3. Acta Pharmaceutica Sinica B, 2021 in press.

10.Zhongya Sun, Hao Zhang, Yuanyuan Zhang, Liping Liao, Wen Zhou, Fengcai Zhang, Fulin Lian, Jing Huang, Pan Xu, Rukang Zhang, Wenchao Lu, Mingrui Zhu, Hongru Tao, Hong Ding, Shijie Chen, Liyan Yue, Bing Zhou, Naixia Zhang, Minjia Tan, Chuanpeng Liu*, Bo Liu*, Kaixian Chen, Hualiang Jiang, Yongjun Dang*, and Cheng Luo*. Covalent inhibitors allosterically block the activation of Rho family proteins and suppress cancer cells invasion. Advanced Science 2020;7(14):2000098.

11.Ye F, Huang J, Wang H*, Luo C*, Zhao K*. Targeting epigenetic machinery: Emerging novel allosteric inhibitors. Pharmacol Ther. 2019 Dec;204:107406.

12.Peng J, Li J, Huang J, Xu P, Huang H, Liu Y, Yu L, Yang Y, Zhou B, Jiang H, Chen K, Dang Y, Zhang Y*, Luo C*, Li G*.p300/CBP inhibitor A-485 alleviates acute liver injury by regulating macrophage activation and polarization. Theranostics. 2019;9(26):8344-8361

13.Jinbao Zhang, Shenghai Chang, Pan Xu, Miao Miao, Hangjun Wu, Youyi Zhang, Tongtong Zhang, Han Wang, Jilin Zhang, Chun Xie, Nan Song, Cheng Luo*, Xing Zhang*, Shujia Zhu*. Structural basis of the proton sensitivity of human GluN1/GluN2A NMDA receptors. Cell Rep. 2018 Dec 26;25(13):3582-3590

14.ChenHong Ding, LiangZhi Wen, Shi-Jie Chen, Chuan Yin, Kai Ding, Shu-Juan Lei, JinPei Liu, FeiChen, Jin He, Kaixian Chen, Hualiang Jiang, Xin Zhang, Cheng Luo*, Wei-Fen Xie*. The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1. Molecular Cancer 2018; Feb 21;17(1):63.

15.Jiangmei Li, Zhen Gao, Dan Zhao, Lunfeng Zhang, Xinhua Qiao, Yingying Zhao, Hong Ding, Panpan Zhang, Junyan Lu, Jia Liu, Hualiang Jiang, Cheng Luo* and Chang Chen*. PI-273, a substrate-competitive, specific small molecule inhibitor of PI4KIIα, inhibits the growth of breast cancer cells. Cancer Research. 2017 Nov 15;77(22):6253-6266
16.Junyan Lu, Chenxiao Jianga, Xiaojing Lia, Lizhi Jiang, Zengxia Li, Tilman Schneider-Poetsch, Kunqian Yu, Jun O. Liu, Hualiang Jiang, Cheng Luo*, Yongjun Dang*. The Inter-domain Linker of eIF4AI Regulates ATP Hydrolysis Coupled Duplex Unwinding, Nucleic Acids Res. 2015 Oct 12. pii: gkv1033.

17.Lulu Hu, Junyan Lu, Jingdong Cheng, Qinhui Rao, Ze Li, Haifeng Hou, Zhiyong Lou, Lei Zhang, Wei Li, Wei Gong, Mengjie Liu, Chang Sun, Xiaotong Yin, Jie Li, Xiangshi Tan, Pengcheng Wang, Yinsheng Wang, Dong Fang, Qiang Cui, Pengyuan Yang, Chuan He, Hualiang Jiang, Cheng Luo* and Yanhui Xu*, Structural Insight into Substrate Preference for TET-mediated Oxidation. Nature 2015 Nov 5; 527(7576): 118-22.

18.Jing Wang#, Cheng Luo#, Changliang Shan, Shannon Elf, Junyan Lu, Yu Zhou, Yi Wen, Yuxin Xie, Jan L Vinkenborg, Jun Fan, Heebum Kang, Dali Han, Jason Karpus, Shijie Chen, Shisheng Ouyang, Chihao Luan, Naixia Zhang, Maarten Merkx, Hong Liu, Jing Chen*, Hualiang Jiang*, Chuan He*, Inhibition of human copper trafficking significantly attenuates tumor growth. Nature Chem; 2015 Dec; 7(12): 968-79.

19.Xiangqian Kong, Jian Liu, Lianchun Li, Liyan Yue, Lihong Zhang, Hualiang Jiang, Xin Xie*, Cheng Luo*, Functional Interplay Between the RK motif and Linker Segment Dictates Oct4-DNA Recognition, Nucleic Acids Res 2015;43(9):4381-92.

20.Yue Huang, Jingli Yan, Qi Li, Jiafei Li, Shouzhe Gong, Hu Zhou, Jianhua Gan, Hualiang Jiang, Gui-Fang Jia*, Cheng Luo*, and Cai-Guang Yang* Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res 2015; 43(1):373-84.