研究方向
宋保亮主要從事膽固醇代謝平衡調控的研究，其研究方向包括：膽固醇合成的負反饋調控；飲食膽固醇吸收的分子機制；細胞內膽固醇的運輸；新型降脂化合物的研發等。已在國際學術期刊上發表研究論文30餘篇，其中作為通訊作者在《Nature Medicine》發表1篇、《Cell Metabolism》發表4篇、《PNAS》發表1篇等。
因為揭示了膽固醇代謝平衡調控的分子機制，為控制高膽固醇血症及其相關疾病提供了新策略而獲得陳嘉庚青年科學獎生命科學獎。
我們主要從事與心腦血管疾病發生密切相關的膽固醇代謝平衡調控的研究。首次提出並證明了小腸細胞對飲食膽固醇吸收的分子模型，發現了該途徑中的多個蛋白因子；深入探索了內源膽固醇合成的負反饋調控機制—HMGCR蛋白的受控降解，揭示了肝臟脂質合成與棕色脂肪能量代謝的聯繫；構建了基於膽固醇合成負反饋調控途徑的篩選體系，並獲得了能同時降低膽固醇和甘油三酯的活性化合物白樺酯醇。這些原創性成果不僅豐富了膽固醇代謝平衡調控的基礎理論，並且對研發新型的降脂藥物具有重要意義。
主要研究方向包括：1）小腸膽固醇吸收的分子途徑；2）細胞內膽固醇動態運輸的分子機制；3）膽固醇代謝調控的信號轉導途徑和機理；4）膽固醇代謝的藥靶系統及新藥研發。
實驗室的長期目標是揭示膽固醇代謝的分子機制，發展治療膽固醇相關疾病的新策略。
個人經歷
1993－1997 南京大學生物科學與技術系，學士
1997－2002 中科院上海生命科學研究院生物化學與細胞生物學研究所，博士
2002－2005 美國德克薩斯大學西南醫學中心，博士後
2005－2014 中科院上海生命科學研究院生物化學與細胞生物學研究所，研究組長，研究員，博士生導師，“百人計畫”擇優支持，“百人計畫”終期評估優秀。分子生物學國家重點實驗室副主任（2012-2014），生化細胞所所長助理（2013-2014）。
2014－至今 武漢大學生命科學學院，教授，院長
2017年5月，獲得全國創新爭先獎。
學術兼職
2009－至今 中國生物物理學會理事會理事
2010－至今 J. of Molecular Cell Biology, Associate Editor
2012－至今 J. Biol. Chem., Editorial Board Member
2014－2016 International Conference on the Bioscience of Lipids (ICBL) 籌劃委員
2014－至今 中國生物化學與分子生物學理事會，常務理事
人物成就
國家傑出青年科學基金（2009）
國家重大科學研究計畫首席科學家（2009）
中科院優秀研究生指導教師（2010）
陳嘉庚青年科學獎（首屆，2012）
萬人計畫科技創新領軍人才入選者（2012）
中科院優秀研究生指導教師（2013）
亞太Arthur Kornberg Memorial Award（2013）
新世紀百千萬人才工程國家級人選（2013）
中國青年科技獎（2013）
談家楨生命科學創新獎（2014）
長江學者特聘教授（2015）
中國細胞生物學學會-普洛麥格創新獎（2015）
個人作品
Representative Publications:
1) Chu BB, Liao YC, Qi W, Xie C, Du X, Wang J, Yang H, Miao HH, Li BL and Song BL*. Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts. Cell, 161(2):291-306, 2015
2) Li PS, Fu ZY, Zhang YY, Xu CQ, Ma YT, Li BL and Song BL*. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nature Medicine, 20(1): 80-86, 2014
3) Liu TF, Tang JJ, Li PS, Shen Y, Li JG, Miao HH, Li BL* and Song BL*. Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis. Cell Metabolism, 16: 213-225, 2012
4) Tang JJ, Li JG, Qi W, Qiu WW, Li PS, Li BL and Song BL*. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metabolism, 13: 44-56, 2011
5) Ge L, Wang J, Qi W, Miao HH, Cao J, Qu YX, Li BL and Song BL*. The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1. Cell Metabolism,7: 508-519, 2008
6) Cao J, Wang J, Qi W, Miao HH, DeBose-Boyd RA, Wang J, Li BL* and Song BL*. Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism. Cell Metabolism, 6:115-128, 2007
7) Ge L, Qi W, Wang LJ, Miao HH, Qu YX, Li BL and Song BL*. Flotillins play an essential role in Niemann-Pick C1 Like 1-mediated cholesterol uptake. PNAS, 108(2): 551-6, 2011
8) Song BL, Sever N, and DeBose-Boyd RA. Gp78, a membrane anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Molecular Cell. 19(6):829-840, 2005
9) Song BL, Javitt NB, and DeBose-Boyd RA. Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol. Cell Metabolism, 1: 179-189, 2005
10) Sever N#, Song BL#, Yabe D#, Goldstein JL, Brown MS, and DeBose-Boyd RA. Insig-dependent ubiquitination and degradation of mammalian 3-Hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol. J Biol Chem, 278: 52479-52490, 2003
Other Publications:
11) Wei J, Fu ZY, Li PS, Miao HH, Li BL, Ma YT, Song BL*. The Clathrin Adaptor Proteins ARH, Dab2, and Numb Play Distinct Roles in Niemann-Pick C1-Like 1 Versus Low Density Lipoprotein Receptor-mediated Cholesterol Uptake. J Biol Chem, 289(48):33689-700, 2014
12) Jiang W, Tang JJ, Miao HH, Qu YX, Qin J, Xu J, Yang J, Li BL, Song BL*. Forward Genetic Screening for Regulators Involved in Cholesterol Synthesis Using Validation-Based Insertional Mutagenesis. PLoS One, 9(11):e112632, 2014
13) Jiang W, Song BL*. Ubiquitin ligases in cholesterol metabolism. Diabetes Metab J. 38(3):171-80, 2014
14) Rogers MA, Liu J, Song BL, Li BL, Chang CC, Chang TY. Acyl-CoA: cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators. J Steroid Biochem Mol Biol. S0960-0760(14): 00207-6, 2014
15) Xiao X*, Song BL. SREBP: a novel therapeutic target.Acta Biochim Biophys Sin (Shanghai).45(1):2-10, 2013
16) Song BL*. A special issue on 'Metabolism'. Acta Biochim Biophys Sin (Shanghai).45(1):1, 2013
17) Xu J, Hu G, Lu M, Xiong Y, Li Q, Chang CC, Song BL, Chang TY, Li BL. MiR-9 reduces human acyl-coenzyme A:cholesterol acyltransferase-1 to decrease THP-1 macrophage-derived foam cell formation.Acta Biochim Biophys Sin (Shanghai).45(11):953-62, 2013
18) Lu M, Hu XH, Li Q, Xiong Y, Hu GJ, Xu JJ, Zhao XN, Wei XX, Chang CC, Liu YK, Nan FJ, Li J, Chang TY, Song BL*, Li BL*.A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth.J Mol Cell Biol. 5:404-15,2013
19) Hu GJ, Chen J, Zhao XN, Xu JJ, Guo DQ, Lu M, Zhu M, Xiong Y, Li Q, Chang CC, Song BL, Chang TY, Li BL. Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene.Cell Res. 23(8):1007-24, 2013
20) Liu Y, Xu XH, Chen Q, Wang T, Deng CY, Song BL, Du JL, Luo ZG. Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development.Nat Commun. 4:2005.2013
21) Xie C, Zhou ZS, Li N, Bian Y, Wang YJ, Wang LJ, Li BL* and Song BL*. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. J Lipid Res, 53: 2092-2101, 2012
22) Wang LJ and Song BL*. Niemann-Pick C1-Like 1 and cholesterol uptake. Biochim Biophys Acta, 1821(7):964-72, 2012
23) Xie C, Li N, Chen ZJ, Li BL, Song BL*. The small GTPase Cdc42 interacts with Niemann-Pick C1 Like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol dependent manner.J Biol Chem, 286(41):35933-42, 2011
24) Zhang JH, Ge L, Qi W, Zhang L, Miao HH, Li BL, Yang M and Song BL*. The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. J Biol Chem, 286(28): 25088-97, 2011
25) Wang LJ, Wang J, Li N, Ge L, Li BL and Song BL*. Molecular characterization of the NPC1L1 variants identified from cholesterol low absorbers. J Biol Chem, 286(9): 7397-7408, 2011
26) Miao HH, Jiang W, Ge L, Li BL, Song BL*. Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2. Acta Biochim Biophys Sin, 42(5): 303-310, 2010
27) Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL and Song BL*. Requirement of Myosin Vb/Rab11a/Rab11-FIP2 complex in cholesterol-regulatedtranslocation of Niemann-Pick C1 Like 1 protein to the cell surface. J Biol Chem, 284: 22481-90, 2009.
28) Wang J, Chu BB, Ge L, Li BL, Yan Y* and Song BL*. Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption. J Lipid Res, 50: 1653-62, 2009
29) Lei L, Xiong Y, Chen J, Yang JB, Wang Y, Yang XY, Chang CCY, Song BL, Chang TY and Li BL*. TNF-alpha stimulates the ACAT1 expressionin differentiating monocytes to promote the CE-laden cell formation. J Lipid Res, 50: 1057-67, 2009
30) Zhao XN, Chen J, Lei L, Hu GJ, Xiong Y, Xu JJ, Li Q, Yang XY, Chang C, Song BL, Chang TY and Li BL. The optional long 5'-untranslated region of human ACAT1 mRNAs impairs the production of ACAT1 protein by promoting its mRNA decay. Acta Biochim Biophys Sin, 41: 30-41, 2009
31) Chen J, Zhao XN, Yang L, Hu GJ, Lu M, Xiong Y, Yang XY, Chang CC, Song BL, Chang TY, Li BL. RNA secondary structures located in the interchromosomal region of human ACAT1 chimeric mRNA are required to produce the 56-kDa isoform. Cell Res, 18: 921-936, 2008
32) Qi W and Song BL*. Dissecting the NPC1L1-mediated cholesterol absorption. Future Lipidology, 3: 481-484, 2008
33) Cao J, Qi W and Song BL*. Tocotrienols and the regulation of cholesterol biosynthesis. Chapter 18 (p237-256) In:Tocotrienols: Beyond Vitamin E,CRC press, 2008
34) Lee JN, Song BL, DeBose-Boyd RA, Ye J. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J Biol Chem, 281:39308-39315, 2006
35) Song BL* and Debose-Boyd RA*. Insig-dependent ubiquitination and degradation of 3-Hydroxy-3-methylglutaryl-Coenzyme A stimulated by {delta}- and {gamma}-Tocotrienols. J Biol Chem, 281: 25054-25061, 2006
36) Song BL, Wang CH, Yao XM, Yang L, Zhang WJ, Wang ZZ, Zhao XN, Yang JB, Qi W, Yang XY, Inoue K, Lin ZX, Zhang HZ, Kodama T, Chang CC, Liu YK, Chang TY and Li BL. Human acyl-CoA:cholesterolacyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma. Bio chem J, 394: 617-626, 2006
37) Yao XM, Wang CH, Song BL, Yang XY, Wang ZZ, Qi W, Lin ZX, Chang CC, Chang TY andLi BL. Two human ACAT2 mRNA variants produced by alternative splicing and coding for novel isoenzymes. Acta Biochim Biophys Sin, 37: 797-806, 2005
38) Sever N, Lee PCW, Song BL, Rawson RB, and DeBose-Boyd RA. Isolation of mutant cells lacking Insig-1 through selection with SR-12813, an agent that stimulates degradation of 3-Hydroxy-3-methylglutaryl-Coenzyme A reductase. J Biol Chem, 279: 43136-43147, 2004
39) Song BL and Debose-Boyd RA. Ubiquitination of 3-Hydroxy-3-methylglutaryl-CoA reductase in permeabilized cells mediated by cytosolic E1 and a putative membrane-bound ubiquitin ligase. J Biol Chem, 279: 28798-28806, 2004
