个人简历

2005年毕业于德国哈勒－维腾贝格大学，获博士学位。2005年至2006年，德国纽伦堡－埃朗根大学生化系，博士后；2006年至2008年，英国邓迪大学／英国医学研究理事会蛋白磷酸化研究所，博士后；2008年至2011年，英国邓迪大学／英国医学研究理事会蛋白磷酸化研究所，副研究员；2012年至今，南京大学模式动物研究所，教授；现任南京大学模式动物研究所所长、南京大学－南京生物医药研究院院长。
基金种类\t基金项目名称
国家自然科学基金　31271498　TBC1D1/14-3-3相互作用在四型葡萄糖转运体细胞质膜转移过程中的功能研究
国家自然科学基金　31571211　AS160在葡萄糖代谢稳态调控中的功能及作用机理研究

研究领域

代谢生理与疾病
胰岛素抵抗是2型糖尿病发病的主要原因，与肥胖、非酒精性脂肪肝等代谢疾病也密切相关。本实验室主要研究生理或病理条件下胰岛素敏感性的调控机制以及胰岛素抵抗的分子机理；采用包括蛋白质组学、代谢组学、生物化学、细胞生物学以及分子生理学等在内的实验手段，结合小鼠基因敲入和基因敲除模型，旨在发现胰岛素敏感性调节的关键分子、发展改善胰岛素敏感性的新策略；同时，实验室也围绕改善或恢复胰岛素敏感性研发治疗2型糖尿病及其并发症的新型药物。""

近期论文

1. Targeting RalGAPα1 in skeletal muscle to simultaneously improve postprandial glucose and lipid control. Science Advances DOI: 10.1126/sciadv.aav4116 (* corresponding author)
2. Quan C, Li M, Du Q, Chen QL, Wang H, Campbell D, Fang L, Xue B, MacKintosh C, Gao X, Ouyang KF, Wang HY and Chen S* (2018) SPEG controls calcium re-uptake into the sarcoplasmic reticulum through regulating SERCA2a by its second kinase-domain. Circ Res DOI: 10.1161/CIRCRESAHA.118.313916 (* corresponding author)
3. Wang J, Hao JW, Wang X, Guo H, Sun HH, Lai XY, Liu LY, Zhu M, Wang HY, Li YF, Yu LY, Xie C, Wang HR, Mo W, Zhou HM, Chen S, Liang G, Zhao TJ. (2019) DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane. Cell Rep 26(1): 209-221.
4. Kang D, Wang D, Xu J, Quan C, Guo X, Wang H, Luo J, Yang Z, Chen S*, Chen J*. (2018) The InR/Akt/TORC1 Growth-Promoting Signaling Negatively Regulates JAK/STAT Activity and Migratory Cell Fate during Morphogenesis. Dev Cell 44:524-531 e525 (* corresponding author)
5. Hao F.Q., Tian M.M., Feng Y.P., Quan C., Chen Y.X., Chen S. and Wei M. (2018) Abrogation of lupus nephritis in somatic hypermutation-deficient MRL/lpr mice. J Immunol 200(12): 3905-3912
6. Chen Q, Rong P, Xu D, Zhu S, Chen L, Xie B, Du Q, Quan C, Sheng Y, Zhao TJ, Li P, Wang HY*, Chen S* (2017) Rab8a deficiency in skeletal muscle causes hyperlipidemia and hepatosteatosis via impairment of muscle lipid uptake and storage. Diabetes 66(9): 2387-2399 (* corresponding author)
7. Chen L., Chen Q.L., Rong P. Wang H.Y.* and Chen S.* (2017) The energy sensing LKB−AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R−PKB pathway in primary hepatocytes. FEBS J 284(13): 2096-2109 (* corresponding author)
8. Chen QL, Xie BX, Zhu SS, Rong P, Sheng Y, Ducommun S, Chen L, Quan C, Li M, Sakamoto K, MacKintosh C, Chen S* and Wang HY* (2017) A TBC1D1Ser231Ala knockin mutation partially impairs 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside- but not exercise-induced muscle glucose uptake in mice. Diabetologia 60(2): 336-345 (* corresponding author)
9. Zhou S., Lu W.L., Chen L., Ge Q.T., Chen D.Y., Xu Z.H., Shi D.Q., Dai J., Li J.X., Ju H.X., Cao Y., Qin J.Z., Chen S., Teng H.J. and Jiang Q. (2017) AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice. Scientific Reports 7: 43245. DOI: 10.1038/srep43245
10. Xie B.X., Chen Q.L., Chen L., Sheng Y., Wang H.Y.* and Chen S.* (2016) The inactivation of RabGAP function of AS160 promotes lysosomal degradation of GLUT4 and causes postprandial hyperglycemia and hyperinsulinemia. Diabetes 65(11):3327-3340 (* corresponding author)
11. Chen L., Chen Q.L., Xie B.X., Quan C., Sheng Y., Zhu S.S., Rong P., Zhou S.L., Sakamoto K., MacKintosh C., Wang H.Y. * and Chen S.* (2016) Disruption of the AMPK–TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion. PNAS 113(26): 7219-24 (* corresponding author)
12. Wang HY*, Quan C, Hu CX, Xie BX, Du YN, Chen L, Yang W, Yang L, Chen QL, Shen B, Hu B, Zheng ZH, Zhu HB, Huang XX, Xu GW and Chen S (2016) A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model. Biology Open 5(7), 979-986
13. Jiang T.T., Gao X.J., Wu C, Tian F, Lei Q.C., Bi J.C., Xie B.X., Wang H.Y., Chen S.*, Wang X.Y.* (2016) Apple-derived pectin modulates gut microbiota, improves gut barrier function, and attenuates metabolic endotoxemia in rats with diet-induced obesity. Nutrients 8(3). pii: E126. doi: 10.3390/nu8030126. (* corresponding author)
14. Li M., Quan C., Toth R., Campbell D.G., MacKintosh C.*, Wang H.Y.* and Chen S.* (2015) Fasting and systemic insulin signaling regulate phosphorylation of brain proteins that modulate cell morphology and link to neurological disorders. J Biol. Chem. 290(50):30030-41 (* corresponding author)
15. Quan C., Xie B.X., Wang H.Y.* and Chen S.*. (2015) PKB-mediated Thr649 phosphorylation of AS160/TBC1D4 regulates the R-wave amplitude in the heart. Plos One 10(4):e0124491. Doi:10.1371/journal.pone.0124491
16. Alvarez-Dominguez J.R., Bai Z.Q., Yuan B.B., Xu D., Lo K.A., Slavov N., Chen S., Lodish H.F. and Sun L. (2015) De novo Reconstruction of Adipose Tissue Transcriptomes Reveals Novel Long Non-coding RNAs that Regulate Brown Adipocyte Development, Cell Metabolism, 21(5): 764-76
17. Tao W., Wu J., Xie B.X., Zhao Y.Y., Shen N., Jiang S., Wang X.X., Xu N., Jiang C., Chen S., Gao X., Xue B., Li C.J. (2015) Lipid-induced muscle insulin resistance is mediated by GGPPS via modulation of the RhoA/Rho kinase signaling pathway. J Biol Chem. 290(33): 20086-97.
18. Wu L., Xu D., Zhou L., Xie B., Yu L., Yang H., Huang L., Ye J., Deng H., Yuan Y.A. Chen S., Li P. (2014) Rab8a-AS160-MSS4 regulatory circuit controls lipid droplet fusion and growth. Dev Cell 30(4): 378-93
19. Chen Q.L., Quan C., Xie B.X., Chen L., Zhou S.L., Toth R., Campbell D.G., Lu S.S., Shirakawa R., Horiuchi H., Li C.J., Yang Z.Z., MacKintosh C., Wang H.Y.* and Chen S.*. (2014) GARNL1, a major RalGAP a subunit in skeletal muscle, regulates insulin-stimulated RalA activation and GLUT4 trafficking via interaction with 14-3-3 proteins. Cell Signal 26(8): 1636-1648 (* corresponding author)
20. Wang H.Y., Ducommun S., Quan C., Xie B.X., Li M., Wasserman D.H., Sakamoto K., MacKintosh C.* and Chen S.* (2013) AS160 deficiency causes whole-body insulin resistance via composite effects in multiple tissues. Biochem J. 449 (2): 479-489 (* corresponding author)
21. Ducommun S, Wang H-Y, Sakamoto K, MacKintosh C and Chen S* (2012) Thr649Ala-AS160 knockin mutation does not impair contraction/AICAR-induced glucose transport in mouse muscle. Am J Physiol Endocrinol Metab 302: E1036-E1043 (* corresponding author)
22. Chen S, Synowsky S, Tinti M and MacKintosh C (2011) The capture of phosphoproteins by 14-3-3 proteins mediates actions of insulin. Trends Endocrinol Metab 22(11):429-36
23. Johnson C, Tinti M, Wood NT, Campbell DG, Toth R, Dubois F, Geraghty KM, Wong BH, Brown LJ, Tyler J, Gernez A, Chen S, Synowsky S, Mackintosh C. (2011) Visualization and biochemical analyses of the emerging mammalian 14-3-3-phosphoproteome. Mol Cell Proteomics 10(10): M110.005751
24. Chen S*, Wasserman D, MacKintosh C and Sakamoto K (2011) Mice with AS160/TBC1D4 Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking. Cell Metabolism 13(1): 68-79 (* corresponding author)
25. Chen S* and MacKintosh C (2009) Differential regulation of NHE1 phosphorylation and glucose uptake by inhibitors of the ERK pathway and p90RSK in 3T3-L1 adipocytes. Cell Signal, 21(12): 1984-93 (* corresponding author)
26. Dubois F., Vandermoere F., Gernez A., Murphy J., Toth R., Chen S., Geraghty K., Morrice N. and MacKintosh C. (2009) Differential 14-3-3-affinity capture reveals new downstream targets of PI 3-kinase signalling. Mol Cell Proteomics, 8(11): 2487-99
27. Pehmøller C., Treebak J.T., Birk J.B., Chen S., Mackintosh C., Hardie D.G., Richter E.A., Wojtaszewski J.F. (2009) Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 297(3):E665-75
28. Treebak J.T., Frøsig C., Pehmøller C., Chen S., Maarbjerg S.J., Brandt N., Mackintosh C., Zierath J.R., Hardie D.G., Kiens B., Richter E.A., Pilegaard H. and Wojtaszewski J.F. (2009) Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle. Diabetologia. 52(5):891-900
29. Babraj J.A., Mustard K., Sutherland C., Towler M.C., Chen S., Smith K., Green K., Leese G., Hardie D.G., Rennie M.J. and Cuthbertson D.J. (2009) Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status. Am J Physiol Endocrinol Metab. 296(5): E1042-8
30. Chen S., Murphy J., Toth R., Campbell D.G., Morrice N.A. and MacKintosh C. (2008) Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J. 409(2): 449-459
31. Geraghty K*., Chen S*., Harthill J.E., Ibrahim A.F., Toth R., Morrice N.A., Vandermoere F., Moorhead G.B., Hardie D.G. and MacKintosh C. (2007) Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to insulin-like growth factor 1, EGF, PMA and AICAR. Biochem J. 407(2): 231-241. (* co-first author)
32. Chen S., Hajirezaei M.R,, Zanor M.-I., Hornyik C., Debast S., Lacomme C., Fernie A. R., Sonnewald U. and Börnke F. (2008) Silencing of sucrose-phosphatase in transgenic potato (Solanum tuberosum) leads to unexpected changes in tuber carbohydrate metabolism following cold storage. Plant, Cell and Environment 31(1): 165-176
33. Hedtke B., Alawady A., Chen S., Boernke F. and Grimm B. (2007) HEMA RNAi silencing reveals a control mechanism of ALA biosynthesis on Mg chelatase and Fe chelatase. Plant Mol. Biol. 64(6):733-742.
34. Chen S., Hajirezaei M. and Börnke F. (2005) Differential expression of sucrose-phosphate synthase isoenzymes in Nicotiana tabacum reflects their functional specialization during dark-governed starch breakdown in source leaves. Plant Physiology 139: 1163 – 1174
35. Chen S., Hajirezaei M.R., Tschiersch H., Peisker M., Sonnewald U. and Börnke F. (2005) Decreased sucrose-6-phosphate phosphatase level in transgenic tobacco inhibits photosynthesis, alters carbohydrate partitioning and inhibits growth. Planta 221: 479 – 492
36. Chen S., Hofius D., Sonnewald U. and Börnke F. (2003) Temporal and spatial control of gene silencing in transgenic plants by inducible expression of double-stranded RNA. Plant J. 36: 731 – 740
37. 陈帅，曹守云，A.Martinez，田文忠，陈受宜，储成才 (2002) alc基因开关系统在水稻中的建立和优化。科学通报 47 (5): 366-369
38. Chen S., Qu N., Cao S.-Y., Bauwe H., Chen S.-Y., Tian W.-Z. and Chu C.-C. (2001) Expression pattern of gdcsP promoter from C3-C4 intermediate plant Flaveria anomala in transgenic rice. Chinese Sci Bull., 46 (19): 1635-1638