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研究员

花芳

职 称:研究员、准聘副教授

所属科室:药理学研究室

导师类别:博士生导师

联系方式:huafang@imm.ac.cn

所属重点实验室:天然药物活性物质与功能国家重点实验室;新药作用机制研究与药效评价北京市重点实验室

个人简介

1. 工作经历
 2017.12-2019.3,美国密歇根大学医学院,外科及免疫系,访问学者,邹伟平教授实验室
 2018.12-今,中国医学科学院药物研究所,药理室,研究员
 2014.9-2018.11,中国医学科学院药物研究所,药理室,副研究员
 2005.8-2014.8,中国医学科学院药物研究所,药理室,助理研究员
2. 教育背景
 2000.9-2005.7,中国医学科学院&北京协和医学院,基础医学研究所,生物化学与分子生物学,理学博士,导师:袁建刚教授。
 1995.9-2000.7,复旦大学,临床医学,医学学士。
近5年针对糖尿病人群肿瘤罹患风险增高,且愈后不佳这一关键临床问题开展系统研究,率先证实代谢应激诱导的TRIB3蛋白是连接代谢紊乱和肿瘤进展的关键“分子桥梁”。确认了以TRIB3为核心的多个关键蛋白相互作用(Protein-protein interaction, PPI)靶点,并自主研发了靶向上述靶点的多肽先导化合物。为阐明代谢紊乱的促肿瘤机制、寻找干预策略提供了理论基础和物质准备。目前累计发表60余篇学术论文,其中SCI论文50余篇,总影响因子超过600。以第一作者或通讯作者身份发表SCI论文17篇,这些成果先后发表在Cancer Discov, Gastroenterology, Nat Commun,Autophagy等国际主流期刊,总影响因子超过150;单篇最高影响因子39.4。

研究方向

肿瘤既要适应复杂的微环境因素(例如营养匮乏等代谢因素;以及复杂的炎症因素),对其作出应答以保证存活;同时还需要改变自身代谢方式以满足快速增殖需要。因此肿瘤对环境变化的适应性以及肿瘤本身的代谢方式改变是肿瘤研究的核心和重点。本课题组主要从事肿瘤分子药理研究,重点关注炎症和代谢异常对肿瘤内在特性(癌基因信号、干性)和抗肿瘤免疫应答的影响,并探索潜在治疗策略。主要包括: 1)肿瘤如何将微环境中的炎症、代谢信号转变为促进生长和转移“促癌信号”? 2)肿瘤如何将微环境中的炎症、代谢信号转变为逃避药物以及免疫系统杀伤的“防御信号”? 3)肿瘤如何通过改变自身代谢方式获得生长优势或逃避免疫杀伤? 4)靶器官的急、慢性炎症损伤通过何种机制进展到肿瘤发生阶段? 5)在阐明上述科学问题分子机制基础上,发现新药靶、并开发针对上述靶点的创新药物。

发表论文


1. Li K#*, Zhang TT#, Zhao CX#, Wang F, Cui B, Yang ZN, Lv XX, Yeerjiang Z, Yuan YF, Yu JM, Wang ZH, Zhang XW, Yu JJ, Liu SS, Shang S, Huang B, Hua F*, Hu ZW*. Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability. Sci Transl Med. 13(586):eabb2914, 2021.(IF=16.3)
2. Du W#, Hua F#, Li X, Zhang J, Li S, Wang W, Zhou J, Wang W, Liao P, Yan Y, Li G, Wei S, Grove S, Vatan L, Zgodzinski W, Majewski M, Wallner G, Chen H, Kryczek I, Fang JY, Zou W*. Loss of optineurin drives cancer immune evasion via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation. Cancer Discov. doi: 10.1158/2159-8290.CD-20-1571, 2021.(IF=39.3)
3. Yu JJ#, Zhou DD#, Yang XX, Cui B, Tan FW, Wang J, Li K, Shang S, Zhang C, Lv XX, Zhang XW, Liu SS, Yu JM, Wang F, Huang B, Hua F*, Hu ZW*; TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target. Nat Commun., 11(1): 3660, 2020. (IF: 12.12)
4. Yu JJ#, Zhou DD#, Cui B, Zhang C, Tan FW, Chang S, Li K, Lv XX, Zhang XW, Shang S, Xiang YJ, Chen F, Yu JM, Liu SS, Wang F, Hu ZW*, Hua F*. Disruption of the EGFR-SQSTM1 interaction by a stapled peptide suppresses lung cancer via activating autophagy and inhibiting EGFR signaling. Cancer Lett. 474:23-35, 2020. (IF: 7.36)
5. Hua F#, Shang S#, Yang YW, Zhang HZ, Xu TL, Yu JJ, Zhou DD, Cui B, Li K, Lv XX, Zhang XW, Liu SS, Yu JM, Wang F, Zhang C, Huang B, Hu ZW*. TRIB3 Interacts with Beta-catenin and TCF4 to Increase Stem Cell Features of Colorectal Cancer Stem Cells and Tumorigenesis. Gastroenterology. 156(3):708-721, 2019. (IF: 20.77)
6. Hua F, Li K, Shang S, Wang F, Hu Z. Immune Signaling and Autophagy Regulation. Adv Exp Med Biol. 1206:551-593, 2019. (IF: 2.126)
7. Li K#, Zhang TT#, Wang F, Cui B, Zhao CX, Yu JJ, Lv XX, Zhang XW, Yang ZN, Huang B, Li X, Hua F*, Hu ZW*. Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression. Oncogene. 37(22):2967-2981, 2018 (Corresponding author) (IF: 6.854)
8. Hua F, Shang S, Hu ZW*. Seeking new anti-cancer agents from autophagy-regulating natural products. J Asian Nat Prod Res. 19(4):305-313, 2017. (IF: 1.091)
9. Shang S#, Hua F#, Hu ZW*. The regulation of β-catenin activity and function in cancer: therapeutic opportunities. Oncotarget. 8:33972-33989, 2017 (Contributed equally) (IF: 5.168)
10. Hua F, Yu JJ, Hu ZW*. Diabetes and cancer, common threads and missing links. Cancer Lett, 374:54-61, 2016. (6.375)
11. Hua F#, Li K#, Yu JJ#, Lv XX, Yan J, Zhang XW, Sun W, Lin H, Shang S, Wang F, Cui B, Mu R, Huang B, Jiang JD, Hu ZW*. TRB3 links insulin/IGF to tumour promotion by interacting with p62 and impeding autophagic/proteasomal degradation functions. Nat Commun., 6:7951, 2015. (11.329)
12. Hua F, Li K, Yu JJ, Hu ZW*. The TRIB3-SQSTM1 interaction mediates metabolic stress-promoted tumorigenesis and progression via suppressing autophagic and proteasomal degradation. Autophagy, 11:1929-1931, 2015. (9.108)
13. Hua F, Hu ZW*. TRIB3-P62 interaction, diabetes and autophagy. Oncotarget. 6:34061-34062, 2015. (5.008)
14. Hua F#, Shi MJ#, Zhu XL#, Li M, Wang HX, Yu XM, Li Y, Zhu CJ*. Transport and uptake of clausenamide enantiomers in CYP3A4-transfected Caco-2 cells: An insight into the efflux-metabolism alliance. Biochem Pharmacol. 98:224-230, 2015. (IF: 5.091)
15. Klionsky DJ, …, Hua F,…Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 2021 Autophagy. 17(1):1-382, 2021. (IF: 16.01)
16. Li K#, Wang F#, Yang ZN, Zhang TT, Yuan YF, Zhao CX, Yeerjiang Z, Cui B, Hua F, Lv XX, Zhang XW, Yu JJ, Liu SS, Yu JM, Shang S, Xiao Y, Hu ZW*. TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation. Nat Commun. 11(1):6316, 2020. (IF: 12.12)
17. Yu JM#, Sun W#, Wang ZH#, Liang X, Hua F, Li K, Lv XX, Zhang XW, Liu YY, Yu JJ, Liu SS, Shang S, Wang F, Yang ZN, Zhao CX, Hou XY, Li PP, Huang B, Cui B*, Hu ZW*. TRIB3 Supports Breast Cancer Stemness by Suppressing FOXO1 Degradation and Enhancing SOX2 Transcription. Nat Commun 10:5720, 2019. (IF: 11.878)
18. Liu SS#, Lv XX#, Liu C, Qi J, Li YX, Wei XP, Li K, Hua F, Cui B, Zhang XW, Yu JJ, Yu JM, Wang F, Shang S, Zhao CX, Hou XY, Yao ZG, Li PP, Li X, Huang B, Hu ZW*. Targeting Degradation of the Transcription Factor C/EBPβ Reduces Lung Fibrosis by Restoring Activity of the Ubiquitin-Editing Enzyme A20 in Macrophages. Immunity 51:522-534, 2019 (IF: 21.52)
19. Zhang XW#, Zhou JC#, Peng D, Hua F, Li K, Yu JJ, Lv XX, Cui B, Liu SS, Yu JM, Wang F, Jin CC, Yang ZN, Zhao CX, Hou XY, Huang B, Hu ZW*. Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation. Autophagy 16(5):782-796, 2020 (IF: 9.77)
20. Liu P, Bao HY, Jin CC, Zhou JC, Hua F, Li K, Lv XX, Cui B, Hu ZW, Zhang XW*. Targeting Extracellular Heat Shock Protein 70 Ameliorates Doxorubicin-Induced Heart Failure Through Resolution of Toll-Like Receptor 2-Mediated Myocardial Inflammation. J Am Heart Assoc. 8:e012338, 2019. (IF: 4.66)
21. Li K, Zhang TT, Hua F, Hu ZW*. Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action. Autophagy. 2018;14(7):1278-1279. (IF: 11.1)
22. Jin W, Cui B, Li PP, Hua F, Lv XX, Zhou JC, Hu ZW, Zhang XW*, 1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via promoting regulatory T cell-mediated resolution of inflammation. Acta Pharm Sin B. 8:178-187, 2018. (IF: 5.808)
23. Li K#, Wang F#, Cao WB, Lv XX, Hua F, Cui B, Yu JJ, Zhang XW, Shang S, Liu SS, Yu JM, Han MZ, Huang B, Zhang TT, Li X, Jiang JD, Hu ZW*. TRIB3 Promotes APL Progression through Stabilization of the Oncoprotein PML-RARα and Inhibition of p53-Mediated Senescence. Cancer Cell. 31:697-710, 2017. (IF: 27.4)
24. Yu JM#, Sun W, Hua F, Xie J, Lin H, Zhou DD, Hu ZW*. BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. Cancer Lett. 365:190-200, 2015. (5.992)

专著


自噬——生物学与疾病基础卷,第三版。秦正红主编,科学出版社,2021
Autophagy: Biology and Disease, Basic Science. Zheng-Hong Qin Editor, Springer, Science Press Beijing, 2019.
自噬——生物学与疾病基础卷,第二版。秦正红主编,科学出版社,2015
应用分子药理学(第二版),王晓良主编,中国协和医科大学出版社,2015

专利


胡卓伟,花芳,尚爽,杨雨薇,陈菲。一种基于阻断PD-1/PD-L1的抗肿瘤药物组合物及其应用。CN201910952044.7,申请日:2019-09-30
胡卓伟,花芳,尚爽,杨雨薇,余娇娇,周丹丹,张诚。靶向抑制Wnt/b-Catenin信号活性的多肽及其用途。CN201810113195.9,申请日:2018-02-05
胡卓伟,花芳,余娇娇,崔冰,周丹丹。一种多肽在制备治疗和预防肿瘤的药物中的应用。CN201810192178.9,申请日:2018-03-09
胡卓伟,花芳,李珂,杨潇骁,余娇娇,尚爽,李博。一类订书肽化合物及其药物组合物的用途。CN201710472196.8,申请日:2017-06-21
胡卓伟,李珂,花芳,吕晓希,余娇娇。与TRB3蛋白特异性结合的多肽,其筛选方法、鉴定和用途。ZL201310206907.9;申请日:2013-05-30,授权日:2020-07-14,
胡卓伟,付小明,李珂,花芳,一种特异结合TRB3的多肽在治疗或预防腹主动脉瘤中的应用。ZL201410183997.9,申请日:2014-05-04,授权日:2020-07-14
胡卓伟,林珩,刘晓波,李珂,花芳。一种多肽或其衍生物在预防和/或治疗高血压性心肌肥厚中的应用。ZL201610262690.7,申请日:2016-04-25,授权日:2020-07-14。

科技奖励


吕琪、胡卓伟、花芳、薛箭飞、秦晓静、孙志广;死亡效应蛋白DEDD抑制实体肿瘤生长、转移的机制及治疗策略;军队科学技术进步奖;二等奖;2017。
花芳;施维雅青年药理学工作者奖;2016。
胡卓伟,花芳,张晓伟,吕晓希,林珩,崔冰,李珂;免疫-自噬调节异常参与纤维化和肿瘤发病的机制研究及药靶发现;教育部自然科学奖;二等奖;2016。
胡卓伟,花芳,张晓伟,吕晓希,林珩,王子艳,吕琪,杨红振;TLRs介导的免疫-自噬调节纤维化和肿瘤发生发展的机制及药靶发现,中华医学科技奖;三等奖;2016。
胡卓伟,花芳,林珩,张晓伟,吕晓希,王子艳;TLRs介导的免疫-自噬调节纤维化和肿瘤发生发展的机制及药靶发现,北京市科学技术奖;三等奖,2016。