王陳繼

發布時間：2021-12-10瀏覽次數：10282

教師基本信息

姓名：王陳繼

職稱：副研究員

電子郵箱：chenjiwang@fudan.edu.cn

辦公地點：生命科學樓C515室

辦公電話：021-31246559

研究方向

1. 研究惡性腫瘤高頻突變基因（特別是泛素-蛋白酶體途徑相關基因）在腫瘤中的作用機製，闡明其致癌機理，並探索其成為腫瘤 “精準治療”分型依據和藥物靶標的可能性；2. 研究泛素-蛋白酶體、自噬體、溶酶體、線粒體和囊泡運輸等相關途徑基因突變導致人類神經/代謝性遺傳病、神經退行性疾病的分子機製及靶向治療的策略。

個人簡介

男，1981年出生，博士，副研究員，博士生導師。2004年畢業於四川大學理科創新班，獲理學學士學位；2010年畢業於万博英超狼队网官方网 ，獲理學博士學位；2010年7月至2016年6月任万博英超狼队网官方网 科研助理（助理研究員）；2016年7月至2017年11月任万博英超狼队网官方网 青年副研究員，2017年12月任万博英超狼队网官方网 副研究員。近年來承擔國家自然基金六項，重點研發計劃子課題二項及校級課題二項。作為通訊作者在《Nature Medicine》、《Nature Communications》、《Science Advances》、 《Cell Death& Differentiation》、《Nucleic Acids Research》、《Leukemia》、《cancer Research》、《Autophagy》和《Redox Biology》等學術期刊發表SCI論文40餘篇。

授課情況

承擔本科生課程《生命的基石-細胞概論》、《人類醫學分子遺傳學》的教學工作。

招生專業

遺傳學

科研項目

  1. 國家自然科學基金重大研究計劃集成項目，糖脂代謝重編程驅動腫瘤細胞周期進程的作用與機製，2024.1-2026.12，在研，參加。

  2. 國家自然科學基金麵上項目，TBCK突變引起RAB5依賴性囊泡運輸缺陷導致神經發育障礙的機製研究, 2024.01 - 2027.12，在研，主持。

  3. 上海市母胎醫學重點實驗室開放課題，胎盤特異表達基因XAGE2參與孕酮合成代謝調控的分子機製, 2023.1-2024.12，在研，主持。

  4. 國家重點研發計劃項目,特定環境條件下幹細胞對心血管功能的重塑, 2023.1-2027.3，在研，參加。

  5. 上海市自然科學基金麵上項目, KCTD7基因突變導致神經元蠟樣脂褐質沉積症的分子機製, 2022.4-2025.3在研，主持。

  6. 國家自然科學基金麵上項目，延胡索酸水合酶基因突變激活Keap1-mTORC2-AKT信號通路促腎癌的分子機製及靶向治療策略，2020.1- 2023.12，，在研，主持。

代表性論文和論著：

  1. 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.

  2. Gao K§, Xu X, Wang C§. Excessive mitophagy drives FBXL4 mutation-caused mitochondrial DNA depletion syndrome. Trends Mol Med. 2023.

  3. 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.

  4. 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. (§並列通訊作者)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.  

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.  

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.


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