|  Appointment: Professor, Dean Department: Biochemistry Research: Cholesterol metabolism and metabolic diseases Location: College of Life Sciences, Room 1134 Email: blsong@whu.edu.cn Education 1993－1997 B.S. Biology, Nanjing University, Nanjing, China 1997－2002 Ph.D. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Professional Experience
2002－2005 Post-doctoral research fellow, UT Southwestern Medical Center, Mentors: Drs. Mike Brown, Joe Goldstein, Russell DeBose-Boyd 2005－2014 Principle Investigator, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. 2014－now Professor and Dean, College of Life Sciences, Wuhan University, Wuhan, China
Academic memberships：
2009－today The Biophysical Society of China, director
2010－today J. of Molecular Cell Biology, Associate Editor
2012－today J. Biol. Chem., Editorial Board Member
2014－2016 International Conference on the Bioscience of Lipids (ICBL) ,member
2014－today The Chinese Society of Biochemistry and Molecular Biology，executive director
Research Description
Dr. Song’s lab works on cholesterol homeostasis that is closely related to cardiovascular disease. His group has dissected the molecular pathway of intestinal cholesterol absorption and identified most of the protein in this process. He has uncovered the mechanism of sterol-regulated degradation of HMG-CoA reductase, which is a major feed-back regulation of de novo cholesterol biosynthesis. His group also identified betulin, a small molecule, which can decrease both cholesterol and fatty acid levels by inhibiting SREBP pathway.
Ongoing projects in this laboratory include:
1) Dissecting the molecular pathway of dietary cholesterol absorption.
2) Studying mechanism and function of intracellular cholesterol trafficking.
3) Uncovering the regulatory mechanisms of cholesterol metabolism.
4) Screening for small chemical compounds controlling cholesterol metabolism.
The long-term goals of these studies are to reveal the molecular mechanism of cholesterol metabolism and develop novel strategies to treat cholesterol-related diseases.
Publications
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 Article about Professor Song Baoliang:http://en.whu.edu.cn/info/1050/1857.htm |
