姓名：刘浥
博士职称
E-MAIL: liuyee@fudan.edu.cn

研究方向
1.探索分子生物钟调控糖脂代谢的机制及其在2型糖尿病发病机理中的作用
2.基于分子机制建立筛选体系以寻找改善糖脂代谢的先导性小分子化合物
重要学术贡献
（1）发现肝糖异生关键转录复合物CREB/CRTC2的调节机理，以及分子生物钟重要因子CRY1抑制其活性的机制（Nature 2007, 2008，Nature Med 2010，均为第一/共同第一作者），这些研究对体内生物钟调控糖代谢机制具有重要启示作用，并为防治2型糖尿病提供了全新的思路和靶点。
（2）发现禁食饥饿通过glucagon-CREB/CRTC2信号通路上调分子生物钟关键转录因子BMAL1在肝脏中的表达，而注射胰岛素则显著抑制这种诱导效果(J Biol Chem 2016，通讯作者)。进一步研究揭示胰岛素可以诱导BMAL1蛋白上的Ser42位点的磷酸化，从而影响其在细胞内的定位。这一调控机理在牵引饮食改变生物钟振荡信号发生过程中有着的关键作用，为理解生物钟信号的发生机制提供了重要理论基础（Nat Commu 2016，通讯作者）。
发表论文
1.Dang, F. Wu, R., Wang, P., Wu, Y., Azam, S., Liu Y*. Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism. (2016) Scientific Report. 6:36926; doi: 10.1038/srep36926
2.Dang, F., Sun, X., Ma, X., Wu, R., Zhang, D., Chen, Y., Xu, Q., Wu, Y., Liu Y*. Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock. (2016) Nature Communications. 7:12696; Doi:10.1038/ncomms12696.
3.Ma X, Zhou Z, Chen Y, Wu Y, Liu Y*. (2016) RBP4 functions as a hepatokine in the regulation of glucose metabolism by the circadian clock in mice. Diabetologia. 59(2):354-62.
4.Sun, X., Dang, F., Zhang, D., Yuan, Y., Zhang, C., Wu, Y., Wang, Y., Liu, Y*., (2015) Glucagon-CREB/CRTC2 Signaling Cascade Regulates Hepatic BMAL1 Protein. J Biol Chem. 290(4):2189-97.
5.Zhang, E.E., Liu, Y., Dentin, R., Pongsawakul, P.Y., Liu, A.C., Hirota, T., Nusinow, D.A., Sun, X., Landais, S., Kodama, Y., Brenner, D.A., Montminy, M., Kay, S.A. (2010) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nature Medicine 16:1152-1156. (co-first authors)
6.Wang, Y., Inoue, H., Ravnskjaer, K., Viste, K., Miller, N., Liu, Y., Hedrick, S., Vera, L., Montminy, M. (2010) Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity. Proc Natl Acad Sci U S A. 107(7):3087-92.
7.Liu, Y., Dentin, R., Chen, D., Hedrick, S., Ravnskjaer, K., Schenk, S., Milne, J., Meyers, D.J., Cole, P., Yates, J.R. 3rd., Olefsky, J., Guarente, L., Montminy, M. (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456, 269-273.
8.Dentin, R., Liu, Y., Koo, S., Hedrick, S., Vargas, T., Heredia, J., Yates, J.R. 3rd., Montminy, M. (2007) Insulin Modulates Gluconeogenesis via Inhibition of the Coactivator TORC2. Nature 449:366-369. (co-first authors)
9.Ravnskjaer, K., Kester, H., Liu, Y., Zhang, X., Lee, D., Yates, J.R. 3rd., Montminy, M. (2007) Cooperative interactions between CBP and TORC2 confer selectivity to CREB target gene expression. EMBO J. 26:2880-2889.
10.Liu, Y., Montminy, M. (2006) CAT in the HAT: catabolic inhibition by the histone acetyltransferase GCN5. Cell Metab. 3:387-388.
11.Fang, X., Hu, S., Xu, B., Snyder, G.D., Harmon, S., Yao, J., Liu, Y., Sangras, B., Falck, J.R., Weintraub, N.L., Spector, A.A. (2006) 14,15-Dihydroxyeicosatrienoic acid activates peroxisome proliferator-activated receptor-alpha. Am J Physiol Heart Circ Physiol. 290:H55-63.
12.Liu, Y., Zhang, Y., Schmelzer, K., Lee, T.S., Fang, X., Zhu, Y., Spector, A.A., Gill, S., Morisseau, C., Hammock, B.D., Shyy, J.Y. (2005) The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc Natl Acad Sci U S A. 102:16747-16752.
13.Fang, X., Hu, S., Watanabe, T., Weintraub, N.L., Snyder, G.D., Yao, J., Liu, Y., Shyy, J.Y., Hammock, B.D., Spector, A.A. (2005) Activation of Peroxisome Proliferator-activated Receptor (alpha) by Substituted Urea-derived Soluble Epoxide Hydrolase Inhibitors. J. Pharmacol. Exp. Ther. 314:260-270.
14.Yeh, M., Cole, A.L., Choi, J., Liu, Y., Tulchinsky, D., Qiao, J.H., Fishbein, M.C., Dooley, A.N., Hovnanian, T., Mouilleseaux, K., Vora, D.K., Yang, W.P., Gargalovic, P., Kirchgessner, T., Shyy, J.Y., Berliner, J.A. Role of sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products. (2004) Circ Res. 95:780-788.
15.Zeng, L., Liao, H., Liu, Y., Lee, T.S., Zhu, M., Wang, X., Stemerman, M.B., Zhu, Y., Shyy, J.Y. Sterol-responsive element-binding protein (SREBP) 2 down-regulate ATP-binding cassette transporter A 1 in vascular endothelial cell: a novel role of SREBP in regulating cholesterol metabolism. (2004) J. Biol. Chem., 279:48801-48807.
16.Liu, Y., Zhu, Y., Rannou, F., Lee, T.S., Formentin, K., Zeng, L., Yuan, X., Wang, N., Chien, S., Forman, B.M., Shyy, J.Y. Laminar Flow Activates Peroxisome Proliferator-Activator Receptor γ in Vascular Endothelial Cells. (2004) Circulation, 110:1128-1133.
17.Lin, T., Zeng, L., Liu, Y., DeFea, K., Schwartz, M.A., Chien, S., Shyy, J.Y. The Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins. (2003) Circ Res., 92:1296-1304.
18.Liu, Y., Chen, B.P., Lu, M., Zhu, Y., Stemerman, M.B., Chien, S., Shyy, J.Y. Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. (2002) Arterioscler. Thromb. Vasc. Biol., 22: 76-81.
19.Yang, L., Kuo, C.B., Liu, Y., Coss, D., Xu, X., Chen, C., Oster-Granite, M.L., Walker, A.M. Administration of unmodified prolactin (U-PRL) and a molecular mimic of phosphorylated prolactin (PP-PRL) during rat pregnancy provides evidence that the U-PRL: PP-PRL ratio is crucial to the normal development of pup tissues. (2001) J. Endocrinol., 168: 227-238.
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申请专利
1.阿特匹灵C及其类似物在制备防治代谢性疾病的药物中的应用，申请号：1.0