王陈继 - 复旦大学 - 生命科学学院

个人简介

男，1981年出生，博士，副研究员，博士生导师。2004年毕业于四川大学理科创新班，获理学学士学位；2010年毕业于复旦大学生命科学学院，获理学博士学位；2010年7月至2016年6月任复旦大学生命科学学院科研助理（助理研究员）；2016年7月至2017年11月任复旦大学生命科学学院青年副研究员，2017年12月任复旦大学生命科学学院副研究员。近年来承担国家自然基金六项，重点研发计划子课题二项及校级课题二项。作为通讯作者在《Nature Medicine》、《Nature Communications》、《Science Advances》、《Cell Death& Differentiation》、《Nucleic Acids Research》、《Leukemia》、《cancer Research》、《Autophagy》和《Redox Biology》等学术期刊发表SCI论文40余篇。科研项目国家自然科学基金重大研究计划集成项目，糖脂代谢重编程驱动肿瘤细胞周期进程的作用与机制，2024.1-2026.12，在研，参加国家自然科学基金面上项目，TBCK突变引起RAB5依赖性囊泡运输缺陷导致神经发育障碍的机制研究, 2024.01 - 2027.12，在研，主持上海市母胎医学重点实验室开放课题，胎盘特异表达基因XAGE2参与孕酮合成代谢调控的分子机制, 2023.1-2024.12，在研，主持国家重点研发计划项目,特定环境条件下干细胞对心血管功能的重塑, 2023.1-2027.3，在研，参加上海市自然科学基金面上项目, KCTD7基因突变导致神经元蜡样脂褐质沉积症的分子机制, 2022.4-2025.3在研，主持国家自然科学基金面上项目，延胡索酸水合酶基因突变激活Keap1-mTORC2-AKT信号通路促肾癌的分子机制及靶向治疗策略，2020.1- 2023.12，，在研，主持

研究领域

1. 研究恶性肿瘤高频突变基因（特别是泛素-蛋白酶体途径相关基因）在肿瘤中的作用机制，阐明其致癌机理，并探索其成为肿瘤 “精准治疗”分型依据和药物靶标的可能性；2. 研究泛素-蛋白酶体、自噬体、溶酶体、线粒体和囊泡运输等相关途径基因突变导致人类神经/代谢性遗传病、神经退行性疾病的分子机制及靶向治疗的策略。

近期论文

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Sun H, Jiao D, Zhao X, Chen Y, Shi Q, Lv Z, Li Y, G Wang C§, Gao K§, mTORC1/S6K1 signaling promotes sustained oncogenic translation through modulating CRL3IBTK-mediated non-degradative ubiquitination of eIF4A1. Elife. 2023. Gao K§, Xu X, Wang C§. Excessive mitophagy drives FBXL4 mutation-caused mitochondrial DNA depletion syndrome. Trends Mol Med. 2023. Gao K§, Chen Y, Wang C§. Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome. Autophagy. 2023 Oct 24:1-3. Chen Y, Jiao D, He H, Sun H, Liu Y, Shi Q, Zhang P, Li Y, Mo R§, Gao K§, Wang C§. Disruption of the Keap1-mTORC2 axis by Cancer-derived Keap1/mLST8 Mutations Leads to Oncogenic mTORC2-AKT Activation. Redox Bio. 2023 Sep 5;67:102872. (§并列通讯作者) Chang K, Chen Y, Zhang X, Zhang W, Xu T, Zeng B, Dai B§, Xu F§, Ye D§, Wang C§. DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma. Cancer Res. 2023 Dec 1;83(23):3940-3955. Chen Y, Jiao D, Liu Y, Xu X, Wang Y, Hexige S, Gao K, Chen Y§, Zhao S§, Ma L§, Wang C§. FBXL4 Mutations Cause Excessive Mitophagy via BNIP3/BNIP3L Accumulation Leading to Mitochondrial DNA Depletion Syndrome. Cell Death Differ. 2023 Oct;30(10):2351-2363. Gao K§, Shi Q, Gu Y, Yang W, He Y, Lv Z, Ding Y, Cao W, Wang C§, Wan X§. SPOP Mutations Promote Tumor Immune Escape in Endometrial Cancer via the IRF1–PD-L1 Axis. Cell Death Differ. 2023 Feb;30(2):475-487. Feng K, Shi Q, Jiao D, Chen Y, Yang W, Su K, Wang Y, Huang Y, Zhang P§, Li Y§, Wang C§. SPOP Inhibits BRAF-dependent Tumorigenesis through Promoting Non-degradative Ubiquitination of BRAF. Cell Biosci. 2022. Dec 30;12(1):211. Wang Y, Wang H§, Wang C§. Lysosomal dysfunction, autophagic defects, and CLN5 accumulation underlie the pathogenesis of KCTD7-mutated neuronal ceroid lipofuscinoses. Autophagy. 2022. Nov 11:1-3. Wang Y, Cao X, Liu P, Zeng W, Peng R, Shi Q, Feng K, Zhang P, Sun H, Wang C§, Wang H§. KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses. Sci Adv. 2022 Aug 5;8(31):eabm5578. Gao K§, Shi Q, Liu Y, Wang C§. Enhanced autophagy and NFE2L2/NRF2 pathway activation in SPOP mutation-driven prostate cancer. Autophagy. 2022 Aug;18(8):2013-2015. Jiao D, Chen Y, Wang Y, Sun H, Shi Q, Zhang L, Zhao X, Liu Y, He H, Lv Z, Liu C, Zhang P, Gao K, Huang Y, Li Y, Li L§, Wang C§. DCAF12 promotes apoptosis and inhibits NF-κB activation by acting as an endogenous antagonist of IAPs. Oncogene. 2022 May;41(21):3000-3010. Shi Q, Jin X, Zhang P, Li Q, He H, Zhao X, Lv Z, Zhao S, Li Y, Gao K§, Wang C§. SPOP Mutations Promote p62/SQSTM1-dependent Autophagy and Nrf2 Activation in Prostate Cancer. Cell Death Differ. 2022 Jun;29(6):1228-1239. Zhang P§, Gao K§, Zhang L, Sun H, Zhao X, Liu Y, Lv Z, Shi Q, Chen Y, Jiao D, Li Y, Gu W§, Wang C§. CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14ARF degradation. Cell Death Differ. 2022 Apr;29(4):758-771. Zhang J, Zhang L, Nie J, Lin Y, Li Y, Xu W, Zhao J, Zhao SM§, Wang C§. Calcineurin Inactivation Inhibits Pyruvate Dehydrogenase Complex Activity and Induces the Warburg Effect. Oncogene. 2021 Dec;40(49):6692-6702. Zhang J, Gao K, Xie H, Wang D, Zhang P, Wei T, Yan Y, Pan Y, Chen H, Shi Q, Yao Li Y, Zhao S, Hou X, Weroha SJ, Wang Y, Zhang J, Karnes RJ, Wang L, Wang C§, Huang H§. SPOP mutation induces DNA methylation via stabilizing GLP/G9a. Nat Comm. 2021 Sep 29;12(1):5716. Ma J, Shi Q, Cui G, Sheng H, Botuyan MV, Zhou Y, Yan Y, He Y, Wang L, Wang Y, Georges Mer§, Ye D§, Wang C§, Huang H§. SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition. Nat Comm. 2021 Oct 1;12(1):5779. Jin X§, Qing S, Li Q, Zhuang H, Shen L, Li J, Qi H, Lin T, Lin Z, Wang J, Cao X, Yang J, Ma Q, Cong L, Xi Y, Fang S, Meng X, Gong Z, Ye M, Wang S§, Wang C§, Gao K§. Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis. Nucleic Acids Res. 2021 Jul 9;49(12):6788-6803. Zhang L, Zhang J, Liu Y, Zhang P, Nie J, Zhao R, Shi Q, Sun H, Jiao D, Chen Y, Zhao X, Huang Y, Li Y, Zhao JY, Xu W, Zhao SM§, Wang C§. Mitochondrial STAT5A promotes metabolic remodeling and the Warburg effect by inactivating the pyruvate dehydrogenase complex. Cell Death Dis. 2021 Jun 19;12(7):634. Jin X, Shi Q, Li Q, Zhou L, Wang J, Jiang L, Zhao X, Feng K, Lin T, Lin Z, Zhuang H, Yang J, Hu C, Zhang L, Shen L, Lu Y, Zhu J, Wang H, Qi H, Meng X, Xi Y, Pan J, Fang S, Tian H, Zhou C, Zhang P, Gao K, Zhao S, Li Y, Gong Z, Wang C§. CRL3-SPOP Ubiquitin Ligase Complex Suppresses the Growth of Diffuse Large B-cell Lymphoma by Negatively Regulating the MyD88/NF-κB Signaling. Leukemia. 2020 May;34(5):1305-1314. Shi Q, Zhu Y, Ma J, Chang K, Ding D, Bai Y, Gao K, Zhang P, Mo R, Feng K, Zhao X, Zhang L, Sun H, Jiao D, Chen Y, Sun Y, Zhao S, Huang H, Li Y§, Ren S§, Wang C§. Prostate Cancer-associated SPOP Mutations Enhance Cancer Cell Survival and Docetaxel Resistance by Upregulating Caprin1-dependent Stress Granule Assembly. Mol Cancer. 2019 Nov 26;18(1):170. Ma J, Peng J, Chang K, Shi Q, Gan H, Gao K, Feng K, Xu F, Zhang H, Dai B, Zhu Y, Shi G, Shen Y, Zhu Y, Qin X, Li Y, Zhang P, Ye D§, Wang C§. SPOP Promotes ATF2 Ubiquitination and Degradation to Suppress Prostate Cancer Progression. J Exp Clin Canc Res. 2018 Jul 11;37(1):145. Gao K§, Zhang Y, Shi Q, Zhang J, Zhang L, Sun H, Jiao D, Zhao X, Tao H, Wei Y, Wang Y, Saiyin H, Zhao S, Li Y, Zhang P§, Wang C§. iASPP–PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation. Cell Death Dis. 2018 May 1;9(5):528. Zhang P, Wang D, Ren S, Zhao Y, Gao K, Ye Z, Wang S, Lin D, Pang X, Pan C, Zhu Y, Yan Y, Wu D, He Y, Zhang J, Lu D, Liu X, Yu L, Zhao S, Li Y, Wang L, Wang Y, Chen Y, Sun Y§, Wang C§, Huang H§. Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nat Med. 2017 Sep;23(9):1055-1062. Zhang P, Gao K, Jin X, Ma J, Peng J, Tang Y, Zhang Y, An J, Yan J, Dong Y, Huang H, Yu L§, Wang C§. Endometrial cancer-associated mutants of SPOP are defective in regulating estrogen receptor-α (ERα) protein turnover. Cell Death Dis. 2015 Mar 12;6:e1687. Gao K, Tang W, Wang D, Zhang P, Yu L, Wang C§, Wu D§. Front Signal-Dependent Accumulation of RHOA Inhibitor FAM65B at Leading Edges Polarizes Neutrophils. J Cell Sci. 2015 Mar 1;128(5):992-1000. Zhang P, Gao K, Tang Y, Jin X, An J, Yu H, Wang H, Zhang Y, Wang D, Huang H, Yu L, Wang C§. Destruction of DDIT3/CHOP protein by wild-type SPOP but not prostate cancer-associated mutants. Hum Mutat. 2014 Sep;35(9):1142-51. An J*, Wang C*, Deng Y, Yu L, Huang H. Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell Rep. 2014 Feb 27;6(4):657-69. Xiao Q*, Qu K*, Wang C*, Kong Y, Liu C, Jiang D, Saiyin H, Jia F, Ni C, Chen T, Zhang Y, Zhang P, Qin W, Sun Q, Wang H, Yi Q, Liu J, Huang H, Yu L. HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas. Gut. 2013 Mar;62(3):440-51.