（1）组蛋白乙酰转移酶GCN5调控糖脂代谢促进胶质母细胞瘤干细胞活力的机制与功能研究

（2）细胞色素氧化酶组装因子COA3调控线粒体重编程影响胶质母细胞瘤干细胞活性的机制及功能研究

（3）靶向SWI/SNF突变肺癌的OXPHOS抑制剂桑黄素的作用及机制研究

（4）靶向线粒体抗癌小分子的临床前优化开发

（5）线粒体抑制剂在消化道肿瘤中的作用和机制研究

现研究方向：线粒体重编程是正常体细胞癌变为肿瘤干细胞的必要条件。揭示线粒体在肿瘤中的作用并进行靶向干预是当前生物医学领域的重点和难点。申请人在这一领域已取得系列研究成果：①解析通透性转换孔介导的胶质瘤干细胞线粒体重编程的机制，揭示线粒体氧化磷酸化是杀死胶质瘤干细胞的有效靶通路；②阐明NNMT-DNMT1轴的活性决定肿瘤对线粒体功能抑制的高敏性，为筛选适合靶向氧化磷酸化抗癌药物的病人提供标志物；③发现特异抑制肿瘤细胞而不抑制正常体细胞氧化磷酸化的抑制剂，已进行胶质瘤国家新药临床试验申请。近5年以一作/通讯（含共同）在Nature、Advanced Science、STTT（2篇）等期刊发表论文4篇，授权国际专利2项，入选上海市海外引进高层次人才计划，担任中国生物物理协会线粒体分会理事。拟以线粒体在肿瘤干细胞中的作用和靶向为重点展开后续研究，以期揭示线粒体在肿瘤中的新功能并获得临床应用抗癌药物。 

出版物：

1)    Emerging phagocytosis checkpointsin cancer immunotherapy. Yu'e Liu; Yanjin Wang; Yanrong Yang; Linjun Weng; QiWu; Lan Fang; Yufeng Shi; Ping Wang SignalTransduction and Targeted Therapy,2023, 8.  SCIE.

2)    Yu’eLiu1#, Chao Chen2#, Xinye Wang1#, Yihong Sun1, Juxiang Chen2*, Yufeng Shi1 * An Epigenetic Role ofMitochondria in Cancer. Cells. 2022 Aug 13;11(16)2518

3)   ChangqingWu1,8, Yu’e Liu1,8, Wenju Liu2,8, Tianhui Zou3,8, Shaojuan Lu1, Chengjie Zhu1,Le He1, Jie Chen1, Lan Fang1, Lin Zou4, Ping Wang1, Lihong Fan5, HongxiangWang6, Juxiang Chen6,*, Jing-Yuan Fang3,*, Cizhong Jiang2,*, Yufeng Shi1,2,9,* NNMT-DNMT1axis is essential for maintaining cancer cell sensitivity to oxidativephosphorylation inhibition. AdvancedScience. 2022 Nov 16:e2202642.

4)    Jin-ZhuWang, Hong Zhu, Pu You, Hui Liu, Wei-Kang Wang, Xiaojuan Fan, Yun Yang, KerenXu, Yingfeng Zhu, Qunyi Li, Ping Wu, Chao Peng, Catherine C.L. Wong, KaichengLi, Yufeng Shi,Nu Zhang, Xiuxing Wang, Rong Zeng, Ying Huang, Liusong Yang, Zefeng Wang, andJingyi Hui. Upregulated YB-1 protein promotes glioblastoma growth through aYB-1/CCT4/mLST8/mTOR pathway. J Clin Invest. 2022 Apr 15; 132(8):e146536

5)   MingLi, Bingjie Hao, Menghuan Zhang, Russel J. Reiter, Tiansheng Zheng, XiangyunChen, Yanbei Ren, Liduo Yue, Baigenzhin Abay, Guojie Chen, Shumeng Lin, XiaoXu, YufengShi#, and Lihong Fan#.  Melatonin enhances radiofrequency induced NKanti-tumor immunity, causing cancer metabolism reprogramming and inhibition ofmultiple pulmonary tumor development.  STTT, 2021Sep; 6(1):330.

6)   ShichaoHuang2, Yu’e Liu1, Yanan Zhang, Ru Zhang, ChengJie Zhu, Lihong Fan, Gang Pei,Bo Zhang, YufengShi.  Baicaleininhibits SARS-CoV-2/VSV replication with interfering mitochondrial oxidativephosphorylation in a mPTP dependent manner. STTT, 2020Nov，(2020) 5:266

7)   Zilai Wang, Daochun Sun, Yu-Jung Chen, Xuanhua Xie, YufengShi,Viviane Tabar, Cameron W. Brennan Tejus Bale, Chenura D. Jayewichreme, Dan R.Laks, Sheila Alcantara Llaguno and Parada LF. Cell lineage-Based Stratificationfor glioblastoma. CancerCell,2020 Sep;

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12) Shi, Y., Stefan, C., Emr, S. Two novel WD40domain-containing protein, Ere1 and Ere2, function in the retromer-mediatedendosomal recycling pathway. MBoC, 2011    Nov;22(21):4093-107.

13)Kang,J*., Shi, Y*., Xiang,B*.,Qu, B., Su, W., Zhu, M., Zhang, M., Bao, G., Wang, F., Zhang, X., et al. Anuclear function of beta-arrestin1 in GPCR signaling regulation of histoneacetylation and gene transcription. Cell2005 123, 833-847.1. (*Theseauthors contributed equally to this paper)