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个人简介

李晓涛,博士,2001年获得美国德克萨斯大学M.D.Anderson癌症中心博士学位,2001年到2005年在美国Baylor医学院做博士后研究,2005至2007年先后在美国Baylor医学院任讲师、助理教授;2007年受聘回国加入华东师范大学。回国后参与重大科学研究计划(973)3项,主持国家自然科学基金重点项目1项,面上项目、国际合作项目4项,国家自然科学基金国家重大研究计划(培育项目)1项,上海市自然科学基金5项,获得上海市浦江人才计划。目前已在Cell、Molecular Cell、PNAS、Cell Metabolism、Nature Communications和Clinical Cancer Research等重要国际学术刊物上发表论文70余篇。Oxidative Medicine and Cellular Longevity杂志和Annals of Hematology & Oncology杂志编委。 教育经历 2001 德克萨斯大学安德森癌症中心 生物医学博士 1995 休斯顿德克萨斯大学健康科学中心 生物科学硕士 1989 重庆医科大学 MD 工作经历 2019 至今 华东师范大学附属长宁妇幼保健院 联合PI 2008 至今 华东师范大学特聘教授 博导 2008 至今 贝勒医学院 Adjunct Faculty 2005-2007 贝勒医学院 讲师、助理教授 2001-2005 伯特莫利教授实验室 博士后 1995-2001 安德森癌症中心威廉姆斯克莱因教授实验室 博士 荣誉及奖励 2015-2018 华东师范大学生命科学学院突出贡献奖 2008 上海市浦江计划

研究领域

主要从事蛋白质代谢与肿瘤发生发展的机制、蛋白质降解的药物研究。 本课题组在REGγ(一种蛋白酶体激活因子)介导的非泛素依赖的蛋白酶体降解通路的研究中首次发现并证实了REGγ蛋白复合体的第一个生物学靶位点。该发现突破了REGγ仅具有降解短肽链模型底物的禁区,并提出了REGγ可以直接降解细胞内完整蛋白的新理论(Cell, 2006)。研究进一步发现REGγ蛋白复合体降解调控细胞周期的靶蛋白(Mol. Cell, 2007)。 近年来主要研究了REGγ在模式动物组织与细胞中的分布及潜在功能(Cell and Mol Life SCI, 2008; JMCB, 2010),完成REGγ对细胞周期调控分子p53的机制研究(JCS, 2010; J Virology, 2010; Sci China Life Sci, 2017),同时展开了REGγ的蛋白质修饰与功能研究(Cell Res, 2011; JBC, 2013)以及REGγ与多种信号通路的相关研究(BMC Cancer, 2012; Nature Communications, 2013),接下来又阐明REGγ在寿命/衰老(PNAS, 2013)、代谢(Cell Metabolism, 2013; Nature Communications, 2016)、氧化应激(Free Radic Biol Med, 2015; Oxid Med Cell Longev, 2017)、脑功能(Neuropsychopharmacology, 2015)方面的作用机制。课题组首次利用体内皮肤肿瘤模型证明REGγ在WNT/β-catenin中的分子调控作用(Nature Communications, 2015)。同时发现REGγ介导的对IκBε的调控作为一种分子机制促成了NFκB激活,并促进了响应慢性损伤的肠道炎症及相关的肿瘤形成(Nature Communications, 2016;Cell Reports, 2016)。最近课题组发现REGγ在结肠癌中的作用机制(2018,Clinical Cancer Research)。 我们今后的研究重点包括:REGγ与蛋白质降解原理及调整的基础理论研究:REGγ与恶性肿瘤发生发展机制的研究;REGγ的病理生理学;REGγ相关的抗癌药物探索;脊椎动物中REGγ的生物学作用。

近期论文

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Xie Y, Gao Y, Gao R, Yang W, Dong Z, Moses RE, Sun A, Li X*, Ge J*. The proteasome activator REGγ accelerates cardiac hypertrophy by declining PP2Acα-SOD2 pathway. Cell Death Differ.2020 Oct;27(10):2952-2972. Zhang B, Zhu X, Tian X, Yang M, Yu Y, Zhou Y, Gao Y, Zhang L, Li Z, Xiao Y, Moses RE, Li X. Procyanidin B2 promotes intestinal injury repair and attenuates colitis-associated tumorigenesis via suppression of oxidative stress in mouse.Antioxid Redox Signal. 2020 Sep 17. Gao X, Wang Q, Wang Y, Liu J, Liu S, Liu J, Zhou X, Zhou L, Chen H, Pan L, Chen J, Wang D, Zhang Q, Shen S, Xiao Y, Wu Z, Cheng Y, Chen G, Kubra S, Qin J, Huang L, Zhang P, Wang C, Moses RE, Lonard DM, O' Malley BW, Fares F, Zhang B, Li X*, Li L*, Xiao J* NIP30, a REGg inhibitor, accentuates anticancer sensitivity in p53-deficient tumor cells. 2020 Nature Communications. 2020 Aug 6;11(1):3904. Xie Y, Li X, Ge J. STAT3-CyPA signaling pathway in endothelial cell apoptosis. Cell Signal. 2020 Jan; 65:109413. Tong L, Shen S, Huang Q, Fu J, Wang T, Pan L, Zhang P, Chen G, Huang T, Li K, Liu Q, Xie S, Yang X, Moses RE, Li X*, Li L*. Proteasome-dependent degradation of Smad7 is critical for lung cancer metastasis. Cell Death Differ. 2019 Nov 26. Wang J, Xing Y, Wang Y, He Y, Wang L, Peng S, Yang L, Xie J, Li X, Qiu W, Yi Z, Liu M. A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer. J Exp Clin Cancer Res. 2019 Oct 22;38(1):422. Zhou L, Yao L, Zhang Q, Xie W, Wang X, Zhang H, Xu J, Lin Q, Li Q, Xuan Y, Ji L, Wang L, Wang W, Wang W, Shi T, Fang L, Zheng B, Li L, Liu S, Zhang B, Li X. REGγ controls Th17 cell differentiation and autoimmune inflammation by regulating dendritic cells. Cell Mol Immunol. 2019 Sep 11. Xie Y, Li X, Ge J. Expression of REGγ in atherosclerotic plaques and promotes endothelial cells apoptosis via the cyclophilin A pathway indicates functional implications in atherogenesis.Cell Cycle. 2019 Sep;18(17):2083-2098. Yao L, Zhou L, Xuan Y, Zhang P, Wang X, Wang T, Meng T, Xue Y, Ma X, Shah AS, Shang S, Ma X, Xie W, Wang H, Fu Q, Xia Y, Moses RE, Wang H, Li L, Xiao J, Zhang B, Li X. The proteasome activator REGγ counteracts immunoproteasome expression and autoimmunity. J Autoimmun. 2019 Sep;103:102282. Xie Y, Li X, Ge J. Cyclophilin A-FoxO1 signaling pathway in endothelial cell apoptosis. Cell Signal. 2019 Sep;61:57-65. Gao X, Chen H, Liu J, Shen S, Wang Q, Clement TM, Deskin BJ, Chen C, Zhao D, Wang L, Guo L, Ma X, Zhang B, Xu Y, Li X*, Li L*. The REGγ-Proteasome Regulates Spermatogenesis Partially by P53-PLZF Signaling. Stem Cell Reports. 2019 Jul 30. pii: S2213-6711(19)30262-0. Jiao C, Li L, Zhang P, Zhang L, Li K, Fang R, Yuan L, Shi K, Pan L, Guo Q, Gao X, Chen G, Xu S, Wang Q, Zuo D, Wu W, Qiao S, Wang X, Moses R, Xiao J, Li L, Dang Y, Li X. REGγ ablation impedes dedifferentiation of anaplastic thyroid carcinoma and accentuates radio-therapeutic response by regulating the Smad7-TGF-β pathway. Cell Death Differ. 2019 Jun 26. Chen S, Wang Q, Wang L, Chen H, Gao X, Gong D, Ma J, Kubra S, Yao X, Li X, Li L, Zhai W, Zheng J. REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma. Cell Death Dis. 2018 May 24;9(6):627 Qingwei Wang, Xiao Gao, Lei Yuan, Tong Yu, etal., Lei Li, Yongyan Dang, Li X. REGγ controls the Hippo-YAP signaling and reciprocal NF-kB–Yap regulation to promote colon cancer. Clinical Cancer Research. 2018 Apr 15;24(8):2015-2025 Zuo Q, Cheng S, Huang W, Bhatti MZ, Xue Y, Zhang Y, Zhang B, Li L, Wu L, Fu J, Chen J, Li X. REGγ Contributes to Regulation of Hemoglobin and Hemoglobin δ Subunit. Oxid Med Cell Longev 2017;2017:7295319. Xu J, Jiao J, Xu W, Ji L, Jiang D, Xie S, Kubra S, Li X, Fu J, Xiao J, Zhang B. Mutant p53 promotes cell spreading and migration via ARHGAP44. Sci China Life Sci 2017 Sep;60(9):1019-1029. Chen S, Wang L, Yao X, Chen H, Xu C, Tong L, Shah A, Huang T, Chen G, Chen J, Liu TL, Li X, Zheng JH, Li L. miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in renal cell carcinoma. Oncotarget 2017 Jul 15;8(38):63986-64000. Dong H, Xu J, Li W, Gan J, Lin W, Ke J, Jiang J, Du L, Chen Y, Zhong X, Zhang D, Yeung SJ, Li X, Zhang H, Reciprocal androgen receptor/interleukin-6 crosstalk drives oesophageal carcinoma progression and contributes to patient prognosis,J Pathol 2017Mar; 241(4): 448-46. Wan Z, Jiang D, Chen S, Jiao J, Ji L, Shah AS, Wei H, Yang X, Li X, Wang Y, Xiao J. T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12. Oncol Rep. 2016 Jul;36(1):306-14. Xu J, Zhou L, Lei Li, Moses RE, O'Malley BW,Li X. The REGgamma-proteasome forms a regulatory circuit with I?Bepsilon and NFκB in experimental colitis. Nature Communications 2016 Feb. 22;7:10761. Sun J, Luan Y, Xiang D, Tan X, Chen H, Deng Q, Zhang J, Chen M, Huang H, Wang W, Niu T, Li W, Peng H, Li S, Li L, Tang W, Li X*, Wu D*, Wang P*. The 11S Proteasome Subunit PSME3 Is a Positive Feedforward Regulator of NF-κB and Important for Host Defense against Bacterial Pathogens. Cell Rep. 2016 Feb 2;14(4):737-49. Klionsky DJ et al (over 1000 authors). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2;12(1):1-222. Fan G, Sun L, Shan P, Zhang X, Huan J, Zhang X, Li D, Wang T, Wei T, Zhang X, Gu X, Yao L, Xuan Y, Hou Z, Cui Y, Cao L, Li X, Zhang S, Wang C. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nature Communications 2015 Oct 6;6:8450. Lv Y, Meng B, Dong H, Jing T, Wu N, Yang Y, Huang L, Moses RE, O'Malley BW, Mei B, Li X. Up-regulation of GSK3β Contributes to Brain Disorders in Elderly REGγ-knockout Mice. Neuropsychopharmacology. 2015 Sept 15. Shuangxi Li, Cong Jiang, Jingjing Pan, Xinbo Wang, Jiali Jin, Linlin Zhao, Weijuan Pan, Guanghong Liao, Xiaopan Cai, Li X, Jianru Xiao, and Ping Wang Regulation of c-Myc protein stability by proteasome activator REGγ. Cell Death and Differentiation. 2015 Jun;22(6):1000-11. Ji L, Xu J, Liu J, Amjad A, Liu Q, Li X. Mutant p53 promotes tumor cell malignancy by both positive and negative regulation of TGF-β pathway. J Biol Chem. 2015 May 1;290(18):11729-40. Yuanyuan Zhang, Shuang Liu, Qiu Hong Zuo, Lin Wu, Lei Ji, Wanli Zhai, Jianru Xiao, Jiwu Chen, and Li X.Oxidative challenge enhances REGγ-proteasome dependent protein degradation. Free Radical Biology & Medicine 2015 May;82:42-9. Amjad Ali, Pei Zhang, Yao Liangfang, Sun Wenshe, Hao Wang, Xia Lin, Yan Dai, Xin-hua Feng, Robb Moses, Daxin Wang, Li X*,Jianru Xiao*. KLF17 empowers TGF-β/Smad signaling by targeting Smad3-dependent pathway to suppress tumor growth and metastasis during cancer progression Cell Death & Disease 2015 Mar 12; 6. Li L, Dang Y, Xiao J, Moses RE, & Li X. (2015). REGg is critical for skin carcinogenesis by modulating Wnt/β-catenin pathway. Nature Communications2015 Apr 24;6:6875. Li X*, Jianping Jin, Weiguo Cao, Carlos Caulin, Robb E. Moses Stresses, Aging, and Age-Related Disorders.Oxidative Medicine and Cellular Longevity2015 Special edition, Vol. 2014 (Article ID 320564). Liu S, Lai L, Zuo Q, Dai F, Wu L, Wang Y, Liu M, Yi Z, Xiao J, Li X. PKA turnover by the REGγ-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis.J Mol Cell Cardiol. 2014 Feb 20; 72C: 28-38. Shi J, Wong J, Piesik P, Fung G, Zhang J, Jagdeo J, Li X, Jan E, Luo H. Cleavage of sequestosome 1/p62 by an enteroviral protease results in disrupted selective autophagy and impaired NFKB signaling.Autophagy. 2013 Aug 13;9 (10). Ali A, Wang Z, Ji L, Liu J, Li L, Yang Y, Wang Y, Zhou L, Guo L, Wang H, Chen J, Caulin C, Myers JN, Fu J, Xiao J, Zhang B, Li X.WT-p53/TGF-β signaling and mutant-p53 differentially regulates REGγ to target ubiquitin/ATP-independent REGγ-proteasome pathway during cancer progression. Nature Communications 2013 4:2667. Dong S, Jia C, Zhang S, Fan G, Xiao W, Shan P, Sun L, Li L, Zheng Y, Liu J, Li Y, Wei H, Hu C, Zhang W, Li Q, Liu J, Jia F, Mo Q, Edwards DP, Huang S, Chan L, O'Malley BW, Li X* and Wang C* The REGγ Proteasome Regulates Hepatic Lipid Metabolism through Inhibition of Autophagy. Cell Metabolism2013 Sep 3;18(3):380-91. Li L, Zhao D, Wei H, Yao L, Dang Y, Amjad A, Xu J, Liu J, Guo L, Li D, Li Z, Zuo D, Zhang Y, Liu J, Huang S, Jia C, Wang L, Wang Y, Xie Y, Luo J, Zhang B, Luo H, Donehower LA, Moses RE, Xiao J, O'Malley BW, Li X. REGγ deficiency promotes premature aging via the casein kinase 1 pathway.ProcNatl Acad Sci U S A. 2013 Jul 2;110(27):11005-10. Liu J, Wang Y, Li L, Zhou L, Wei H, Zhou Q, Liu J, Wang W, Ji L, Shan P, Wang Y, Yang Y, Jung SY, Zhang P, Wang C, Long W, Zhang B, Li X. Site-specific acetylation of the proteasome activator REGγ directs its heptameric structure and functions. J Biol Chem. 2013 Jun 7;288(23):16567-78 Redfern AD, Colley SM, Beveridge DJ, Ikeda N, Epis MR, Li X, Foulds CE, Stuart LM, Barker A, Russell VJ, Ramsay K, Kobelke SJ, Li X, Hatchell EC, Payne C, Giles KM, Messineo A, Gatignol A, Lanz RB, O'Malley BW, Leedman PJ. RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6536-41. Jing He, Long Cui, Yu Zeng, Guangqiang Wang, Li X. (2012). REGγ is associated with multiple oncogenic pathways in human cancers. BMC Cancer. Feb 23; 12(1):75. Qiao S, Murakami K, Zhao Q, Wang B, Seo H, Yamashita H, Li X, Iwamoto T, Ichihara M, Yoshino M. (2012). Mimosine-Induced Apoptosis in C6 Glioma Cells Requires the Release of Mitochondria-Derived Reactive Oxygen Species and p38, JNK Activation. Neurochem Res. Feb;37(2):417-27. Shen J, Zhang S, Li Y, Zhang W, Chen J, Zhang M, Wang T, Jiang L, Zou X, Wong J, Li X, Cui Y, Wang C. (2011). p14(ARF) inhibits the functions of adenovirus E1A oncoprotein. Biochem J. Mar 1;434(2):275-85. Wu Y, Wang L, Zhou P, Wang G, Li X. (2011). Regulation of REGg cellular distribution and function by SUMO modification.Cell Research. 2011 May; 21(5):807-16. Gao G, Wong J, Zhang J, Mao I, Shravah J, Wu Y, Xiao A, Li X*, Luo H*. (2010). Proteasome Activator REGg Enhances Coxsackieviral Infection via Facilitating p53 Degradation. J. Virol.84 (21): 11056-11066. Liu J, Yu G., Zhao P., Wang C., Luo H., Long W., Wang Y., Zhao Y., Tsai M., O'Malley B.W. and Li X. (2010). REGγ modulates p53 activity by regulating its cellular localization. J. Cell Science.123 (pt23): 4076-84. Tian M, Xiaoyi W, Li X, Guosheng R. (2009). Proteasomes reactivator REGγ enchances oncogenicity of MDA-MB-231 cell line via promoting cell proliferation and inhibiting apoptosis.Cell Mol Biol(Noisy-le-grand). 55 Suppl:OL1121-31. Yu G, Zhao Y, He J, Mukherjee A, Mao CA, Li M, and Li X. (2008). Comparative analysis of REGγ expression augurs functional implication. J. Mol. Cell. Biol.Aug; 2(4):192-8. Ivy Mao, Jian Liu, Li X*, Honglin Luo*. (2008). REGg, A Proteasome Activator and Beyond? Cell and Mol Life Sci. Dec;65(24):3971-80. Li X, Larbi Amazit, Weiweng Long, David M. Lonard, John J. Monaco and O’Malley B.W. (2007). Proteolytic turnover of p21 by the REGγ-proteasome pathway. Mol. Cell,26, 831-842 Li X., Lonard D., Jung S.Y., Malovannaya A., Feng Q., Qin J., Tsai S. Y., Tsai M-J., and O’Malley B.W. (2006). The SRC-3/AIB1 coactivator is degraded in an ubiquitin- and ATP-independent manner by the REGgamm-proteasome Cell. 124, 381-392. Verma S., Ismail A., Gao X., Fu G., Li X., O’MalleyB. W., Nawaz Z. (2004). Ubiquitin-conjugating enzyme, UBCH7 act as a coactivator for steroid hormone receptors. Mol. Cell. Biol.24, 8716-26. Li X. Lonard D. M. and O’Malley B. W. (2004). A Contemporary Understanding of Progesterone Receptor Function (Review). Mechanisms of Aging and Development. 125, 669-78. Auboeuf D., Dowhan D.H., Li X., Larkin K., Ko L., Berget S.M., O'Malley B.W.(2004). CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing.Mol. Cell. Biol.24, 442-53. Li X. and O'Malley B.W. Unfolding the action of progesterone receptors (minireview). (2003). J. Biol.Chem.10, 39261-4. Li X., Wong J., Tsai S.Y., Tsai M.J., and O'Malley B.W. (2003). Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification. Mol. Cell. Biol.23, 3763-73. Li X., Bhattacharya C.,Maity S., Dayal S,and Klein W.H. (2002). Ectoderm Gene Activation in Sea Urchin Embryos Mediated by CCAAT Binding Factor CBF. Differentiation. 70, 109-19 Angerer L.M., Oleksyn D. W.,Levine A.M., Li X., Klein W.H. and Angerer R. (2001). Sea urchin goosecoid function links fate specification along the animal-vegetal and oral-aboral embryonic axes. Development. 128, 4393-404 Yuh C., Li X., Davidson E.H., and Klein W.H. (2001). Correct Expression of Spec2a in the Sea Urchin Embryo Requires Both Otx and Other cis-Regulatory Elements. Dev. Biol.232, 424-438 Huang L., Li X., El-Hodiri H.M., Dayal S., Athula H.W., and Klein W.H. (2000). Involvement of Tcf/Lef in Establishing Cell Types along the Animal-Vegetal Axis of Sea Urchins. Dev. Genes Evol.210, 73-81. Li X., Athula HW and Klein WH. (1999). Requirement of SpOtx in Cell Fate Decisions in the Sea Urchin Embryo and Possible Roles as a Mediator of beta-Catenin Signaling. Dev. Biol.212, 425-439 Klein W.H. and Li X. (1998). Function and Evolution of Otx Proteins. Biochem. Biophys. Res. Commun. 258, 22-34 Li X., Chuang C.K., Mao C.A., Angerer L.M., and Klein WH. (1997). Two Otx proteins generated from alternative splicing of multiple transcripts of a single gene in Strongylocentrotuspurppuratus. Dev. Biol.187, 253-266 Chuang C.K., Athula H.W., Mao C.A., Li X. and Klein W.H. (1996). Transient Appearance of S. purpuratus Otx in Micromere Nuclei: Cytoplasmic Retention of SpOtx Mediated Through an alpha-Actinin SH3 Domain. Dev. Genetics19, 231-239 LiX., Weinstock G.M. and Murray B.E. (1995). Generation of Auxotrophic mutants of Enterococcus faecalis. J. Bacteriol.177, 6866-6873 LiX., Qinan Wang. Xingping zheng and Yufu Jiang. (1994). Therapy of refractory infections with the third generation of new antibiotics, Ceftizoxime. Chinese J. Antibiotics. 04, 62-67

学术兼职

中国生物化学协会上海分会副理事长 中国生物化学协会理事 中国衰老协会理事 自然科学基金委优青人才、项目会审评审

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