课题组长
姓名：
范高峰副教授 研究员 博士生导师, PhD, 副教授
职务：
所在院所：
生命科学与技术学院
荣誉称号：
教育经历：
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1999/09—2003/07，南京大学，学士
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2003/09—2009/07，美国新泽西州罗格斯大学，博士
博士后及工作经历：
- 2009/09—2017/01，美国冷泉港国家实验室，博士后
- 2017/02—2023/11， 上海科技大学，生命科学与技术学院，助理教授（Tenure-track）
- 2023/11—至今，上海科技大学，生命科学和技术学院，副教授（Tenured）
课题组简介
研究内容：
（1）研究代谢分子NAD+及其调控通路在肿瘤免疫中的重要作用，重点研究NAD代谢酶的生物学功能以及NAD进出细胞以及细胞器的通道蛋白；
（2）研究酪氨酸磷酸酶 PTPN6/SHP1 在免疫细胞中的重要调控作用； （3）研究酪氨酸激酶和磷酸酶在卵巢癌扩散转移和耐药性方面的重要作用以及分子机制；
研究成果展示
（1）酪氨酸磷酸酶SHP1调控T细胞发育成熟，机制解析有助于肿瘤免疫的理性设计（Nat Struct Mol Biol 2023）； （2）卵巢癌细胞下调PTGES3，解除其产物PGE2对果糖磷酸激酶PFKL别构抑制，增强糖酵解，促进卵巢癌转移 （Cell Reports 2023）； （3）运用蛋白降解技术PROTAC，开发针对酪氨酸激酶FER的蛋白降解剂，抑制卵巢癌细胞运动迁移能力（JBC 2023）； （4）运用蛋白降解技术PROTAC，开发针对NAD生物合成酶NAMPT的专一性靶向降解剂，同时清除胞内iNAMPT和胞外eNAMPT（Cell Chem Bio 2022，封面文章）； （5）酪氨酸激酶FER通过磷酸化IRS4招募PI3K调节亚基PIK3R2，从而上调AKT信号通路促进卵巢癌细胞恶性增殖（eLife 2022）； （6）揭示了肿瘤浸润T细胞内TUBBY-NAMPT-NAD+调控信号通路的重要作用以及提高机体NAD+水平对于肿瘤免疫治疗的协同促进效果（Cell Reports 2021）； （7）酪氨酸磷酸酶 PTPRR 可以去磷酸化β-Catenin，从而下调WNT信号通路，抑制卵巢癌细胞过度生长（JBC 2019）； （8）酪氨酸磷酸酶SHP1在免疫信号通路中发挥重要作用，突变导致的功能失调直接引发皮肤炎症（Immunity 2017）；
（9）酪氨酸激酶 FER 对于卵巢癌的扩散转移起到关键调控作用（Gene Dev，2016）。
代表性论文（*第一作者，#通讯作者）
- 1. Zhang JL(张佳丽)*; Jiang ZZ(江振洲)*; Xueyuan Zhang; Ziqun Yang; Jinjiao Wang; Jialing Chen; Li Chen; Minfang Song; Shengmiao Chen; Xuexue Xiong; Yuetong Wang; Piliang Hao; Tiffany Horng; Min Zhuang; Liye Zhang; Erwei Zuo; Fang Bai; Jie Zheng; Haopeng Wang#; Fan GF(范高峰)#; .THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.NATURE STRUCTURAL & MOLECULAR BIOLOGY. 04 Jan 2024.
- 2. Chen, Shengmiao*; Wu, Yiran; Gao, Yang; Wu, Chenxu; Wang, Yuetong; Hou, Chun; Ren, Miao; Zhang, Shuyuan; Zhu, Qi; Zhang, Jiali; Yao, Yufeng; Huang, Mei; Qi, Yingchuan B.; Liu, Xue-Song; Horng, Tiffany; Wang, Haopeng; Ye, Dan; Zhu, Zhengjiang#; Zhao, Suwen#; Fan, Gaofeng#; .Allosterically inhibited PFKL via prostaglandin E2 withholds glucose metabolism and ovarian cancer invasiveness.CELL REPORTS. 2023. 42(10).
- 3. Yanchun Zhang*; Xuexue Xiong; Renhong Sun; Xiaotong Zhu; Chen Wang; Xiaobao Yang#; Dake Li#; Gaofeng Fan#; .Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness.JOURNAL OF BIOLOGICAL CHEMISTRY. May 2023.
- 4. Zhu, Xiaotong*; Liu, Haixia*; Chen, Li*; Wu, Chenxu; Liu, Xuesong; Cang, Yong; Jiang, Biao#; Yang, Xiaobao#; Fan, Gaofeng#; .Addressing the Enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation.CELL CHEMICAL BIOLOGY. 01 Nov 2022. 29(11).
- 5. Zhang, Yanchun*; Xiong, Xuexue*; Zhu, Qi; Zhang, Jiali; Chen, Shengmiao; Wang, Yuetong; Cao, Jian; Chen, Li; Hou, Linjun; Zhao, Xi; Hao, Piliang; Chen, Jian; Zhuang, Min; Li, Dake#; Fan, Gaofeng#; .FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells.ELIFE. 12 May 2022. 11.
- 6. Wang, Yuetong*; Wang, Fei*; Wang, Lihua*; Qiu, Shizhen*; Yao, Yufeng; Yan, Chenxu; Xiong, Xuexue; Chen, Xuyong; Ji, Quanquan; Cao, Jian; Gao, Ganglong; Li, Dake; Zhang, Liye; Guo, Zhiqian; Wang, Ruoning; Wang, Haopeng#; Fan, Gaofeng#; .NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells.CELL REPORTS. 2021. 36(6).
- 7. Wang, Yuetong*; Cao, Jian; Liu, Weiwei; Zhang, Jiali; Wang, Zuo; Zhang, Yiqun; Hou, Linjun; Chen, Shengmiao; Hao, Piliang; Zhang, Liye; Zhuang, Min; Yu, Yang; Li, Dake#; Fan, Gaofeng#; .Protein tyrosine phosphatase receptor type R (PTPRR) antagonizes the Wnt signaling pathway in ovarian cancer by dephosphorylating and inactivating βcatenin.JOURNAL OF BIOLOGICAL CHEMISTRY. Nov 2019. 294(48):18306-18323.
- 8. 范高峰*; .专访信号转导领域青年学者——范高峰研究员.生命的化学. 15 Mar 2022. 42(03):620-622.
- 9. Chen, Jian*; Qiu, Shizhen; Li, Wentao; Wang, Kun; Zhang, Yu; Yang, Han; Liu, Baichuan; Li, Guangfei; Li, Li; Chen, Min; Lan, Junjie; Niu, Jiahua; He, Peijie; Cheng, Lei; Fan, Gaofeng; Liu, Xin; Song, Xianmin#; Xu, Chenqi#; Wu, Haitao#; Wang, Haopeng#; .Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness.CELL RESEARCH;. 2023.
- 10. Chu, Liping*; Qu, Yuxiu; An, Yang; Hou, Linjun; Li, Juewan; Li, Weijia; Fan, Gaofeng; Song, Bao-Liang; Li, En; Zhang, Liye; Qi, Wei#; .Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer.CELL DEATH & DISEASE. 15 Feb 2022. 13(2).
- 11. Wu, Ruohan*; Chen, Xuyong; Kang, Siwen; Wang, Tingting; Gnanaprakasam, Jn Rashida; Yao, Yufeng; Liu, Lingling; Fan, Gaofeng; Burns, Mark R.; Wang, Ruoning#; .De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function.SCIENCE ADVANCES. Dec 2020. 6(51).
- 12. Li, Wentao*; Qiu, Shizhen; Chen, Jian; Jiang, Shutan; Chen, Wendong; Jiang, Jingwei; Wang, Fei; Si, Wen; Shu, Yilai; Wei, Ping; Fan, Gaofeng; Tian, Ruijun; Wu, Haitao#; Xu, Chenqi#; Wang, Haopeng#; .Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy.IMMUNITY. 18 Aug 2020. 53(2):456-+.
- 13. Chen, Shengmiao*; Yao, Yufeng*; Zhang, Yanchun*; Fan, Gaofeng#; .CRISPR system: Discovery, development and off-target detection.CELLULAR SIGNALLING. Jun 2020. 70.
- 14. Zhang, Jiali*; Wang, Zuo; Zhang, Siwei; Chen, Yanxun; Xiong, Xuexue; Li, Xiaojuan; Tonks, Nicholas K.#; Fan, Gaofeng#; .Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER.CELLULAR SIGNALLING. Oct 2018. 50:100-110.
- 15. Yao, Xiang-Ping*; Cheng, Xuewen; Wang, Chong; Zhao, Miao; Guo, Xin-Xin; Su, Hui-Zhen; Lai, Lu-Lu; Zou, Xiao-Huan; Chen, Xue-Jiao; Zhao, Yuying; Dong, En-Lin; Lu, Ying-Qian; Wu, Shuang; Li, Xiaojuan; Fan, Gaofeng; Yu, Hongjie; Xu, Jianfeng; Wang, Ning#; Xiong, Zhi-Qi#; Chen, Wan-Jin#; .Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification.NEURON. 27 Jun 2018. 98(6):1116-+.
- 16. Zhang, Siwei*; Fan, Gaofeng; Hao, Yuan; Hammell, Molly; Wilkinson, John Erby; Tonks, Nicholas K.#; .Suppression of protein tyrosine phosphatase N23 predisposes to breast tumorigenesis via activation of FYN kinase.GENES & DEVELOPMENT. Oct 2017. 31(19):1939-1957.
- 17. Shang, Wanjing*; Wang, Fei*; Fan, Gaofeng#; Wang, Haopeng#; .Key elements for designing and performing a CRISPR/Cas9-based genetic screen.JOURNAL OF GENETICS AND GENOMICS. 20 Sep 2017. 44(9):439-449.
- 18. Gurung, Prajwal*; Fan, Gaofeng; Lukens, John R.; Vogel, Peter; Tonks, Nicholas K.; Kanneganti, Thirumala-Devi#; .Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1 alpha-Mediated Inflammatory Disease.IMMUNITY. 2017. 46(4):635-648.
- 19. Fan, Gaofeng*; Zhang, Siwei; Gao, Yan; Greer, Peter A.; Tonks, Nicholas K.#; .HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer.GENES & DEVELOPMENT. 2016. 30(13):1542-1557.
- 20. Fan, Gaofeng*; Wrzeszczynski, Kazimierz O.; Fu, Cexiong; Su, Gang; Pappin, Darryl J.; Lucito, Robert; Tonks, Nicholas K.#; .A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines.BIOCHEMICAL JOURNAL. 2015. 465:433-442.
- 21. Fan, Gaofeng*; Aleem, Saadat; Yang, Ming; Miller, W. Todd#; Tonks, Nicholas K.#; .Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase.JOURNAL OF BIOLOGICAL CHEMISTRY. 2015. 290(26):15934-15947.
- 22. Fan, Gaofeng*; Lin, Guang; Lucito, Robert; Tonks, Nicholas K.#; .Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells.JOURNAL OF BIOLOGICAL CHEMISTRY. 2013. 288(34):24923-24934.
- 23. Fan, Gaofeng*; Simmons, Matthew J.; Ge, Sheng; Dutta-Simmons, Jui; Kucharczak, Jerome; Ron, Yacov; Weissmann, David; Chen, Chiann-Chyi; Mukherjee, Chandreyee; White, Eileen; Gelinas, Celine#; .Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.BLOOD. 2010. 115(17):3559-3569.
- 24. Fan, Gaofeng*; Fan, Yongjun; Gupta, Nupur; Matsuura, Isao; Liu, Fang; Zhou, Xiao Zhen; Lu, Kun Ping; Gelinas, Celine#; .Peptidyl-Prolyl Isomerase Pin1 Markedly Enhances the Oncogenic Activity of the Rel Proteins in the Nuclear Factor-kappa B Family.CANCER RESEARCH. 2009. 69(11):4589-4597.
- 25. Dutta, Jui*; Fan, Gaofeng; Gelinas, Celine#; .CAPER alpha Is a Novel Rel-TAD-Interacting Factor That Inhibits Lymphocyte Transformation by the Potent Rel/NF-kappa B Oncoprotein v-Rel.JOURNAL OF VIROLOGY. 2008. 82(21):10792-10802.
- 26. Gupta, Nupur*; Delrow, Jeffrey; Drawid, Amar; Sengupta, Anirvan M.; Fan, Gaofeng; Gelinas, Celine#; .Repression of B-cell linker (BLNK) and B-cell adaptor for phosphoinositide 3-kinase (BCAP) is important for lymphocyte transformation by Rel proteins.CANCER RESEARCH. 2008. 68(3):808-814.
- 27. Fan, Yongjun*; Dutta, Jui; Gupta, Nupur; Fan, Gaofeng; Gelinas, Celine#; .Regulation of programmed cell death by NF-kappa B and its role in tumorigenesis and therapy.ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY. 2008. 615:223-250.
- 28. Simmons, M. J.*; Fan, G.; Zong, W-X; Degenhardt, K.; White, E.; Gelinas, C.#; .Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist.ONCOGENE. 2008. 27(10):1421-1428.
- 29. Dutta, J.*; Fan, Y.; Gupta, N.; Fan, G.; Gelinas, C.#; .Current insights into the regulation of programmed cell death by NF-kappa B.ONCOGENE. 2006. 25(51):6800-6816.
- 30. Liu, XJ*; Huang, YX; Zhang, WJ; Fan, GF; Fan, CH; Li, GX#; .Electrochemical investigation of redox thermodynamics of immobilized myoglobin: Ionic and ligation effects.LANGMUIR. 2005. 21(1):375-378.
专利
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1. 范高峰，王皞鹏，王月桐，王飞，NAD+和/或NAD+抑制剂和/或NAD+激动剂在调节T细胞活性中的用途，国际，PCT/CN2019/090022，发明专利
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2. 范高峰，张佳丽，庄敏，PEPSI: 基于邻近标记技术的新型酪氨酸磷酸酶的底物鉴定方法，中国，202010573873.7，发明专利
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3. 杨小宝，范高峰，姜标，刘海霞，朱小童，基于NAMPT靶蛋白的蛋白降解化合物及其应用，中国，202111025519.1，发明专利
项目
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1. 表观遗传修饰对肠道免疫系统发育和稳态的调节，科技部国家重点研发计划，课题参与人员（课题骨干）
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2. 酪氨酸磷酸酶SHP1新型作用底物THEMIS的鉴定及其在免疫T细胞发育过 程中的功能探究，国家自然科学基金面上项目，项目负责人
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3. 酪氨酸激酶FER促进卵巢癌扩散转移的功能及机制研究，国家自然科学基金面上项目，项目负责人
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4. 新型邻近标记技术PEPSI在寻找酪氨酸磷酸酶底物中的运用，上海市科学技术委员会，项目负责人
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5. NAD+代谢调控在肿瘤免疫中的作用探究，上海市曙光计划，项目负责人
奖励
- 1. 2018，浦江人才
- 2. 2019，东方学者 特聘教授
- 3. 2019，曙光学者
- 4. 2022，东方学者特聘教授 跟踪计划
- 5. 2022，年度优秀教师
课题组成员及合影
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姓名：张佳丽
身份：博士后
在组时间：2023/01-至今
邮箱：zhangjl@@shanghaitech.edu.cn
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姓名：姚钰锋
身份：博士研究生
在组时间：2017/09-2023/12
邮箱：yaoyf1@@shanghaitech.edu.cn
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姓名：陈胜淼
身份：博士研究生
在组时间：2018/01-2024/01
邮箱：chenshm1@@shanghaitech.edu.cn
-
姓名：侯春
身份：博士研究生
在组时间：2020/5-至今
邮箱：houchun@@shanghaitech.edu.cn
-
姓名：黄梅
身份：博士研究生
在组时间：2019/03-至今
邮箱：huangmei@@shanghaitech.edu.cn
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姓名：陈丽
身份：博士研究生
在组时间：2019/03-至今
邮箱：chenli@@shanghaitech.edu.cn
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姓名：张艳春
身份：博士研究生
在组时间：2018/10-至今
邮箱：zhangych3@@shanghaitech.edu.cn
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姓名：江振洲
身份：博士研究生
在组时间：2020/1-至今
邮箱：jiangzhzh@@shanghaitech.edu.cn
-
姓名：朱小童
身份：博士研究生
在组时间：2020/09-至今
邮箱：zhuxt@@shanghaitech.edu.cn
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姓名：王晨
身份：硕士研究生
在组时间：2020/09-2023/12
邮箱：wangchen1@shanghaitech.edu.cn
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姓名：张梦瑶
身份：博士研究生
在组时间：2021/09-至今
邮箱：zhangmy@shanghaitech.edu.cn
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姓名：任苗
身份：硕士研究生
在组时间：2021/09-至今
邮箱：renmiao@shanghaitech.edu.cn
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姓名：陈嘉玲
身份：博士研究生
在组时间：2021/09-至今
邮箱：chenjl2@shanghaitech.edu.cn
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