高翔实验室
实验室：025-58641511
研究所邮箱：gaoxiang at nicemice.cn
研究方向： 本实验室主要研究方向为免疫和代谢对生理稳态的调控及其失调引起的复杂疾病。我们通过基因工程小鼠模型分析多器官或者生物系统来解析生理稳态调控中复杂的基本问题：包括确定大脑、肝脏、脂肪、骨骼、肠道和免疫系统中基因的功能，以及肠道微生物与宿主之间的相互作用。我们希望能够解析这些器官和生物是如何共同工作调节生物体的生理稳态。近年来实验室的工作包括：PP2A-C敲除能够促进肝脏对葡萄糖的处理能力；解析肠道微生物和免疫系统对机体代谢的影响；确定了组蛋白甲基化程度通过下丘脑中雌激素环路影响雌性代谢的机制；在国际上首次证明了Gasdermin家族蛋白的N端在细胞死亡中起关键作用，并通过对脓毒症（Sepsis）模型小鼠的研究，发现了多种Gasdermin相关的细胞焦亡调控机制；通过建立和分析肥胖记忆模型小鼠，首次发现了适应性免疫中的CD4+ T细胞能够储存肥胖记忆。
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1 Liu, Q., M. Li, M. Sun, R. Xin, Y. Wang, Q. Chen, X. Gao, and Z. Lin, Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway. J Mol Cell Biol, 2023.
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2 Li, X., T. Zhang, L. Kang, R. Xin, M. Sun, Q. Chen, J. Pei, Q. Chen, X. Gao, and Z. Lin, Apoptotic caspase-7 activation inhibits non-canonical pyroptosis by GSDMB cleavage. Cell Death Differ, 2023. 30(9): p. 2120-2134.
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3 Guan, F., X. Luo, J. Liu, Y. Huang, Q. Liu, J. Chang, G. Fang, D. Kang, H. Gu, L. Luo, L. Yang, Z. Lin, X. Gao, C. Liu, and J. Lei, GSDMA3 deficiency reprograms cellular metabolism and modulates BCR signaling in murine B cells. iScience, 2023. 26(8).
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4 Kang, L., J. Dai, Y. Wang, P. Shi, Y. Zou, J. Pei, Y. Tian, J. Zhang, V.C. Buranasudja, J. Chen, H. Cai, X.Gao, and Z. Lin, Blocking Caspase-1/Gsdmd and Caspase-3/-8/Gsdme pyroptotic pathways rescues silicosis in mice. PLoS Genet, 2022. 18(12): p. e1010515.
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5 Li, X., M. Sun, H. Qi, C. Ju, Z. Chen, X. Gao, and Z. Lin, Identification of a Chromosome 1 Substitution Line B6-Chr1BLD as a Novel Hyperlipidemia Model via Phenotyping Screening. Metabolites, 2022. 12(12):1276.
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6 Zhao, M., K. Ren, X. Xiong, Y. Xin, Y. Zou, J.C. Maynard, A. Kim, A.P. Battist, N. Koneripalli, Y. Wang,Q. Chen, R. Xin, C. Yang, R. Huang, J. Yu, Z. Huang, Z. Zhang, H. Wang, D. Wang, Y. Xiao, O.C. Salgado,N.N. Jarjour, K.A. Hogquist, X.S. Revelo, A.L. Burlingame, X. Gao, J. von Moltke, Z. Lin, and H.B. Ruan,Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. Immunity, 2022. 55(4): p. 623-638.
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7 Zou, Y., J. Pei, Y. Wang, Q. Chen, M. Sun, L. Kang, X. Zhang, L. Zhang, X. Gao, and Z. Lin, The Deficiency of SCARB2/LIMP-2 Impairs Metabolism via Disrupted mTORC1-Dependent Mitochondrial OXPHOS. Int J Mol Sci, 2022. 23(15):8634.
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8 Chen, Q., J. Zheng, D. Wang, Q. Liu, L. Kang, X. Gao*, and Z. Lin*, Nitrosonisoldipine is a selective inhibitor of inflammatory caspases and protects against pyroptosis and related septic shock. Eur J Immunol, 2021. 51(5): p. 1234-1245.
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9 Zou, D., J. Pei, J. Lan, H. Sang, H. Chen, H. Yuan, D. Wu, Y. Zhang, Y. Wang, D. Wang, Y. Zou, D. Chen, J. Ren, X. Gao, and Z. Lin, A SNP of bacterial blc disturbs gut lysophospholipid homeostasis and induces inflammation through epithelial barrier disruption. EBioMedicine, 2020. 52: p. 102652.
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10 Zheng, J., D. Wang, Q. Chen, Q. Liu, Z. Lin, Q. Hu, X. Wu, X. Gao, Q. Li, and J. Ren, Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N-terminal. Eur J Immunol, 2020. 50(3): p. 464-467.
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11 Zhang, T., P. Xie, Y. Dong, Z. Liu, F. Zhou, D. Pan, Z. Huang, Q. Zhai, Y. Gu, Q. Wu, N. Tanaka, Y. Obata, A. Bradley, C.J. Lelliott, L.M.J. Nutter, C. McKerlie, A.M. Flenniken, M.F. Champy, T. Sorg, Y. Herault, M.H. Angelis, V.G. Durner, A.M. Mallon, S.D.M. Brown, T. Meehan, H.E. Parkinson, D. Smedley, K.C.K. Lloyd, J. Yan, X. Gao, J.K. Seong, C.L. Wang, R. Sedlacek, Y. Liu, J. Rozman, L. Yang, and Y. Xu, High-throughput discovery of genetic determinants of circadian misalignment. PLoS Genet, 2020. 16(1): p. e1008577.
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12 Wang, D., J. Zheng, Q. Hu, C. Zhao, Q. Chen, P. Shi, Q. Chen, Y. Zou, D. Zou, Q. Liu, J. Pei, X. Wu, X. Gao, J. Ren, and Z. Lin, Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis. Cell Death Differ, 2020. 27(2): p. 466-481.
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13 Lloyd, K.C.K., D.J. Adams, G. Baynam, A.L. Beaudet, F. Bosch, K.M. Boycott, R.E. Braun, M. Caulfield, R. Cohn, M.E. Dickinson, M.S. Dobbie, A.M. Flenniken, P. Flicek, S. Galande, X. Gao, A. Grobler, J.D. Heaney, Y. Herault, M.H. de Angelis, J.R. Lupski, S. Lyonnet, A.M. Mallon, F. Mammano, C.A. MacRae, R. McInnes, C. McKerlie, T.F. Meehan, S.A. Murray, L.M.J. Nutter, Y. Obata, H. Parkinson, M.S. Pepper, R. Sedlacek, J.K. Seong, T. Shiroishi, D. Smedley, G. Tocchini-Valentini, D. Valle, C.L. Wang, S. Wells, J. White, W. Wurst, Y. Xu, and S.D.M. Brown, The Deep Genome Project. Genome Biol, 2020. 21(1): p. 18.
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14 Jiang, H., L. Zhang, X. Liu, W. Sun, K. Kato, C. Chen, X. Li, T. Li, Z. Sun, W. Han, F. Zhang, Q. Xiao, Z. Yang, J. Hu, Z. Qin, R.H. Adams, X. Gao, and Y. He, Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation. Arterioscler Thromb Vasc Biol, 2020. 40(4): p. 958-972.
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15 Huang, C., T. Liu, Q. Wang, W. Hou, C. Zhou, Z. Song, Y.S. Shi, X. Gao, G. Chen, Z. Yin, and Y. Hu, Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Developmentdagger. Cereb Cortex, 2020.
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16 Zhou, S., Y. Li, L. Qiao, Y. Ge, X. Huang, X. Gao, H. Ju, W. Wang, J. Zhang, J. Yan, H. Teng, and Q. Jiang, Inactivation of Lkb1 in postnatal chondrocytes leads to epiphyseal growth-plate abnormalities and promotes enchondroma-like formation. FASEB J, 2019. 33(8): p. 9476-9488.
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17 Zheng, M., D. Li, Z. Zhao, D. Shytikov, Q. Xu, X. Jin, J. Liang, J. Lou, S. Wu, L. Wang, H. Hu, Y. Zhou, X. Gao, and L. Lu, Protein phosphatase 2A has an essential role in promoting thymocyte survival during selection. Proc Natl Acad Sci U S A, 2019. 116(25): p. 12422-12427.
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18 Yuan, X., X. Qin, D. Wang, Z. Zhang, X. Tang, X. Gao, W. Chen, and L. Sun, Mesenchymal stem cell therapy induces FLT3L and CD1c(+) dendritic cells in systemic lupus erythematosus patients. Nat Commun, 2019. 10(1): p. 2498.
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19 Xu, Q., X. Jin, M. Zheng, D. Rohila, G. Fu, Z. Wen, J. Lou, S. Wu, R. Sloan, L. Wang, H. Hu, X. Gao, and L. Lu, Phosphatase PP2A is essential for TH17 differentiation. Proc Natl Acad Sci U S A, 2019. 116(3): p. 982-987.
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20 Wang, Y., P. Shi, Q. Chen, Z. Huang, D. Zou, J. Zhang, X. Gao, and Z. Lin, Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation. J Mol Cell Biol, 2019.
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21 Wang, J., R. Xie, X. Kou, Y. Liu, C. Qi, R. Liu, W. You, J. Gao, and X. Gao, A protein phosphatase 2A deficit in the hippocampal CA1 area impairs memory extinction. Mol Brain, 2019. 12(1): p. 51.
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22 Quan, C., M. Li, Q. Du, Q. Chen, H. Wang, D. Campbell, L. Fang, B. Xue, C. MacKintosh, X. Gao, K. Ouyang, H.Y. Wang, and S. Chen, SPEG Controls Calcium Reuptake Into the Sarcoplasmic Reticulum Through Regulating SERCA2a by Its Second Kinase-Domain. Circ Res, 2019. 124(5): p. 712-726.
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23 Ma, P., N.N. Song, Y. Li, Q. Zhang, L. Zhang, L. Zhang, Q. Kong, L. Ma, X. Yang, B. Ren, C. Li, X. Zhao, Y. Li, Y. Xu, X. Gao, Y.Q. Ding, and B. Mao, Fine-Tuning of Shh/Gli Signaling Gradient by Non-proteolytic Ubiquitination during Neural Patterning. Cell Rep, 2019. 28(2): p. 541-553 e4.
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24 Lai, S.S., X. Fu, Q. Cheng, Z.H. Yu, E.Z. Jiang, D.D. Zhao, D.C. Yu, Y.D. Qiu, X. Gao, H.X. Ju, W. Wang, Q. Jiang, M.S. Zhu, C.J. Li, and B. Xue, HSC-specific knockdown of GGPPS alleviated CCl4-induced chronic liver fibrosis through mediating RhoA/Rock pathway. Am J Transl Res, 2019. 11(4): p. 2382-2392.
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25 Giannuzzi, G., P.J. Schmidt, E. Porcu, G. Willemin, K.M. Munson, X. Nuttle, R. Earl, J. Chrast, K. Hoekzema, D. Risso, K. Mannik, P. De Nittis, E.D. Baratz, Y. Herault, X. Gao, C.C. Philpott, R.A. Bernier, Z. Kutalik, M.D. Fleming, E.E. Eichler, and A. Reymond, The Human-Specific BOLA2 Duplication Modifies Iron Homeostasis and Anemia Predisposition in Chromosome 16p11.2 Autism Individuals. Am J Hum Genet, 2019. 105(5): p. 947-958.
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26 Geng, L., X. Tang, K. Zhou, D. Wang, S. Wang, G. Yao, W. Chen, X. Gao, W. Chen, S. Shi, N. Shen, X. Feng, and L. Sun, MicroRNA-663 induces immune dysregulation by inhibiting TGF-beta1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Cell Mol Immunol, 2019. 16(3): p. 260-274.
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27 Gao, J., A. Qin, D. Liu, R. Ruan, Q. Wang, J. Yuan, T.S. Cheng, A. Filipovska, J.M. Papadimitriou, K. Dai, Q. Jiang, X. Gao, J.Q. Feng, H. Takayanagi, C. Zhang, and M.H. Zheng, Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network. Sci Adv, 2019. 5(11): p. eaaw7215.
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28 Dai, J., S. Zhou, Q. Ge, J. Qin, J. Li, H. Ju, Y. Cao, M. Zheng, C. Li, X. Gao, H. Teng, and Q. Jiang, Recruitment of Brd3 and Brd4 to acetylated chromatin is essential for proinflammatory cytokine-induced matrix-degrading enzyme expression. J Orthop Surg Res, 2019. 14(1): p. 59.
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29 Chen, Q., P. Shi, Y. Wang, D. Zou, X. Wu, D. Wang, Q. Hu, Y. Zou, Z. Huang, J. Ren, Z. Lin, and X. Gao, GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity. J Mol Cell Biol, 2019. 11(6): p. 496-508.
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30 Chen, Q., P. Shi, D. Wang, Q. Liu, X. Li, Y. Wang, D. Zou, Z. Huang, X. Gao, and Z. Lin, Epidermis-Activated Gasdermin-A3 Enhances Thermogenesis of Brown Adipose Tissue through IL-6/Stat3 Signaling. Am J Pathol, 2019. 189(5): p. 1041-1052.
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31 - Chen, Q., P. Shi, Y. Wang, D. Zou, X. Wu, D. Wang, Q. Hu, Y. Zou, Z. Huang, J. Ren, Z. Lin, and X. Gao, GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity. J Mol Cell Biol, 2018.
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32 - Dai, J., S. Zhou, Q. Ge, J. Qin, D. Chen, Z. Xu, D. Shi, J. Li, H. Ju, Y. Cao, M. Zheng, C.J. Li, X. Gao, H. Teng, and Q. Jiang, Bi-directional regulation of cartilage metabolism by inhibiting BET proteins-analysis of the effect of I-BET151 on human chondrocytes and murine joints. J Orthop Surg Res, 2018. 13(1): p. 118.
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33 - Geng, L., X. Tang, K. Zhou, D. Wang, S. Wang, G. Yao, W. Chen, X. Gao, W. Chen, S. Shi, N. Shen, X. Feng, and L. Sun, MicroRNA-663 induces immune dysregulation by inhibiting TGF-beta1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Cell Mol Immunol, 2018.
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34 - Geng, L., S. Wang, X. Li, D. Wang, H. Chen, J. Chen, Y. Sun, W. Chen, G. Yao, X. Gao, W. Chen, S. Shi, X. Feng, and L. Sun, Association between Type I interferon and depletion and dysfunction of endothelial progenitor cells in C57BL/6 mice deficient in both apolipoprotein E and Fas ligand. Curr Res Transl Med, 2018. 66(3): p. 71-82.
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35 - Lai, B., J. Zou, Z. Lin, Z. Qu, A. Song, Y. Xu, and X. Gao, Haploinsufficiency of hnRNP U Changes Activity Pattern and Metabolic Rhythms. Am J Pathol, 2018. 188(1): p. 173-183.
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36 - Lin, Z., F. Liu, P. Shi, A. Song, Z. Huang, D. Zou, Q. Chen, J. Li, and X. Gao, Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C. Stem Cell Res Ther, 2018. 9(1): p. 47.
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37 - Lu, K., T. Shi, L. Li, K. Zhang, X. Zhu, S. Shen, F. Yu, H. Teng, X. Gao, H. Ju, W. Wang, and Q. Jiang, Zhuangguguanjie formulation protects articular cartilage from degeneration in joint instability-induced murine knee osteoarthritis. Am J Transl Res, 2018. 10(2): p. 411-421.
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38 - Lu, K., T.S. Shi, S.Y. Shen, W.L. Lu, J. Wu, K.J. Zhang, X.B. Zhu, Y. Shi, X.L. Liu, F. Yu, L. Li, H.J. Teng, X. Gao, H.X. Ju, W. Wang, C.J. Li, Q. Jiang, and B. Xue, Egr1 deficiency disrupts dynamic equilibrium of chondrocyte extracellular matrix through PPARgamma/RUNX2 signaling pathways. Am J Transl Res, 2018. 10(6): p. 1620-1632.
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39 - Luan, X.R., X.L. Chen, Y.X. Tang, J.Y. Zhang, X. Gao, H.P. Ke, Z.Y. Lin, and X.N. Zhang, CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse. Mol Ther Nucleic Acids, 2018. 12: p. 220-228.
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40 - Ma, H., C. Liu, B. Shi, Z. Zhang, R. Feng, M. Guo, L. Lu, S. Shi, X. Gao, W. Chen, and L. Sun, Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis. EBioMedicine, 2018. 32: p. 21-30.
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41 - Moore, B.A., B.C. Leonard, L. Sebbag, S.G. Edwards, A. Cooper, D.M. Imai, E. Straiton, L. Santos, C. Reilly, S.M. Griffey, L. Bower, D. Clary, J. Mason, M.J. Roux, H. Meziane, Y. Herault, C. McKerlie, A.M. Flenniken, L.M.J. Nutter, Z. Berberovic, C. Owen, S. Newbigging, H. Adissu, M. Eskandarian, C.W. Hsu, S. Kalaga, U. Udensi, C. Asomugha, R. Bohat, J.J. Gallegos, J.R. Seavitt, J.D. Heaney, A.L. Beaudet, M.E. Dickinson, M.J. Justice, V. Philip, V. Kumar, K.L. Svenson, R.E. Braun, S. Wells, H. Cater, M. Stewart, S. Clementson-Mobbs, R. Joynson, X. Gao, T. Suzuki, S. Wakana, D. Smedley, J.K. Seong, G. Tocchini-Valentini, M. Moore, C. Fletcher, N. Karp, R. Ramirez-Solis, J.K. White, M.H. de Angelis, W. Wurst, S.M. Thomasy, P. Flicek, H. Parkinson, S.D.M. Brown, T.F. Meehan, P.M. Nishina, S.A. Murray, M.P. Krebs, A.M. Mallon, K.C.K. Lloyd, C.J. Murphy, and A. Moshiri, Identification of genes required for eye development by high-throughput screening of mouse knockouts. Commun Biol, 2018. 1: p. 236.
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42 - Rozman, J., B. Rathkolb, M.A. Oestereicher, C. Schutt, A.C. Ravindranath, S. Leuchtenberger, S. Sharma, M. Kistler, M. Willershauser, R. Brommage, T.F. Meehan, J. Mason, H. Haselimashhadi, I. Consortium, T. Hough, A.M. Mallon, S. Wells, L. Santos, C.J. Lelliott, J.K. White, T. Sorg, M.F. Champy, L.R. Bower, C.L. Reynolds, A.M. Flenniken, S.A. Murray, L.M.J. Nutter, K.L. Svenson, D. West, G.P. Tocchini-Valentini, A.L. Beaudet, F. Bosch, R.B. Braun, M.S. Dobbie, X. Gao, Y. Herault, A. Moshiri, B.A. Moore, K.C. Kent Lloyd, C. McKerlie, H. Masuya, N. Tanaka, P. Flicek, H.E. Parkinson, R. Sedlacek, J.K. Seong, C.L. Wang, M. Moore, S.D. Brown, M.H. Tschop, W. Wurst, M. Klingenspor, E. Wolf, J. Beckers, F. Machicao, A. Peter, H. Staiger, H.U. Haring, H. Grallert, M. Campillos, H. Maier, H. Fuchs, V. Gailus-Durner, T. Werner, and M. Hrabe de Angelis, Identification of genetic elements in metabolism by high-throughput mouse phenotyping. Nat Commun, 2018. 9(1): p. 288.
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43 - Wang, Q., J. Tang, S. Jiang, Z. Huang, A. Song, S. Hou, X. Gao, and H.B. Ruan, Inhibition of PPARgamma, adipogenesis and insulin sensitivity by MAGED1. J Endocrinol, 2018.
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44 - Yu, F., X. Han, K. Zhang, B. Dai, S. Shen, X. Gao, H. Teng, X. Wang, L. Li, H. Ju, W. Wang, J. Zhang, and Q. Jiang, Evaluation of a polyvinyl alcohol-alginate based hydrogel for precise 3D bioprinting. J Biomed Mater Res A, 2018.
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45 - Zou, J., B. Lai, M. Zheng, Q. Chen, S. Jiang, A. Song, Z. Huang, P. Shi, X. Tu, D. Wang, L. Lu, Z. Lin, and X. Gao, CD4+ T cells memorize obesity and promote weight regain. Cell Mol Immunol, 2018. 15(6): p. 630-639.
| 基金种类 | 基金项目名称 |
|---|---|
| 国家重点研发计划项目 | 心血管、代谢性疾病等基因修饰动物模型研发 |
| 国家重点研发计划课题 | 样本库和表型分析大数据数据库建设与质控 |
| 国家自然科学基金面上项目 | 细胞焦亡促进矽肺发生的分子机制研究 |
| 国家自然科学基金面上项目 | 基于野生型来源1号染色体替换系的自发性血脂模型的建立与机制研究 |
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林兆宇 linzy@nicemice.cn
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何亚涛 heyt@nicemice.cn
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陈芊月 chenqy@nicemice.cn
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