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教师简介

宋保亮(Bao-Liang Song)
来源:伟德官网 时间:2016-12-26 10:53:43 阅读量:
    职称职务:教授、院长 
Appointment: Professor, Dean
学科专业:生物化学 
Department: Biochemistry
研究方向:胆固醇代谢与代谢性疾病 
Research: Cholesterol metabolism and metabolic diseases
实验室位置:伟德官网大楼1134房间 
Location: College of Life Sciences, Room 1134
Email: blsong@whu.edu.cn

 

教育经历/Education
1993-1997 南京大学生物科学与技术系,学士
      B.S. Biology, Nanjing University, Nanjing, China
1997-2002 中科院上海生命科学研究院生物化学与细胞生物学研究所,博士
      Ph.D. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological
      Sciences, Chinese Academy of Sciences. 博士

工作经历与任职/Professional Experience
2002-2005  美国德克萨斯大学西南医学中心,博士后
       Post-doctoral research fellow, UT Southwestern Medical Center, Mentors: Drs. Mike
       Brown, Joe Goldstein, Russell DeBose-Boyd

2005-2014  中科院上海生命科学研究院生物化学与细胞生物学研究所,研究组长,研究员,博士生导师。
      分子生物学国家重点实验室副主任(2012-2014),生化细胞所所长助理(2013-2014)
       Principle Investigator, Institute of Biochemistry and Cell Biology, Shanghai Institutes
       for Biological Sciences, Chinese Academy of Sciences.

2014-至今  伟德官网,教授,院长
       Professor and Dean, College of Life Sciences, Wuhan University, Wuhan, China

学术兼职
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) 筹划委员
2018-至今  国家基金委“糖脂代谢的时空网络调控”重大研究计划专家组组长
2019-至今  中国细胞生物学会,副理事长

奖励及荣誉
国家杰出青年科学基金(2009)
陈嘉庚青年科学奖(2012)
万人计划科技创新领军人才入选者(2012)
亚太Arthur Kornberg Memorial Award(2013)
中国青年科技奖(2013)
谈家桢生命科学创新奖(2014)
2015年度中国生命科学领域十大进展(2016)
国务院政府特殊津贴(2016)
首届全国创新争先奖(2017)
药明康德生命化学研究奖杰出成就奖(2018)

研究概述/Research Description
  胆固醇是生命活动必需的脂类物质,并与心脑血管疾病、神经退行性疾病及肿瘤等的发生密切相关,胆固醇代谢是生物医学的前沿领域和药物研发的关键基础。我们长期从事胆固醇代谢研究,取得如下成果:1)阐明一个胆固醇合成的负反馈调控通路与人体胆固醇吸收的分子通路,奠定了当前学术界对这两个代谢途径的认识;2)发现由溶酶体-过氧化物酶体膜接触介导的胆固醇运输新途径,证明膜接触是主要的运输方式,并决定脂质在细胞内的精确分布;3)鉴定蛋白质胆固醇共价修饰新类型,颠覆了20多年来认为Hedgehog是唯一胆固醇修饰蛋白的认识,揭示胆固醇可作为共价配体调控信号转导和发育。以通讯(含共同通讯)作者发表论文30余篇,包括1篇Science、1篇Cell、1篇Nature Medicine、4篇Cell Metabolism、1篇Nature Cell Biology、1篇Molecular Cell、1篇Nature Metabolism。成果被选入十余部英文教材与专著。

Cholesterol is an essential component of mammalian membranes. But high level of circulating cholesterol causes cardiovascular disease. Imbalanced cholesterol metabolism is related to Alzheimer’s disease, cancer and other diseases. Aiming to address fundamental questions in the lipid field and improve human health, we focus on cholesterol metabolism and have made scientific achievements as follows.

1. Regulation of cholesterol biosynthesis and intestinal absorption.
(A)
We identify a rare frameshift variant in the LIMA1 gene from a Chinese Kazakh family with inherited low plasma cholesterol. The loss-of-function mutation of LIMA1 reduces intestinal cholesterol absorption and lower plasma cholesterol, suggesting targeting LIMA1 can be a new way to lower cholesterol level (Science, 2018). (B) We have elucidated the molecular mechanism of intestinal cholesterol absorption. We find that NPC1L1 and Flotillins form cholesterol-rich microdomains in the plasma membrane (PNAS, 2011). When the cholesterol level is high, cholesterol binds to the N-terminal domain of NPC1L1 (JBC, 2011), releasing its C-terminal cytoplasmic tail to recruit the clathrin adaptor Numb and initiating clathrin-mediated endocytosis (Nat Med, 2014). The cholesterol absorption inhibitor ezetimibe blocks cholesterol uptake by impairing NPC1L1 endocytosis (Cell Metab, 2008). Cholesterol and fatty acids stabilize ACAT-2 that increases cholesterol absorption efficiency and prevents lipotoxicity (NCB, 2017). (C) The sterol-regulated degradation of HMG-CoA reductase (HMGCR) and the SREBP pathway are two major feedback regulatory mechanisms governing cholesterol synthesis. Together with others, we have delineated the HMGCR degradation pathway. We identify gp78 and RNF145 as the key E3s catalyzing HMGCR ubiquitination (Mol Cell, 2005; Cell Metab, 2012; JBC, 2018), characterized lanosterol, 24,25-dihydrolanosterol and geranylgeraniol as the endogenous regulators (JBC, 2003; Cell Metab, 2005), reveal that Ufd1 is a cofactor of gp78 (Cell Metab, 2007). (D) Based on these findings, we have developed compounds to treat hyperlipidemia by inhibiting SREBP processing or inducing HMGCR degradation (Cell Metab, 2011; Nat Commun, 2018).

2. Cholesterol transport through lysosome-peroxisome membrane contacts.
Most mammalian cells take up cholesterol from low-density lipoprotein (LDL) through receptor-mediated endocytosis. After reaching lysosomes, LDL-derived cholesterol continues to move to other organelles. However, to where and how cholesterol moves from lysosome are poorly understood. We find that cholesterol can be conveyed through membrane contact sites formed between lysosomal protein synaptotagmin VII (Syt7) and peroxisomal lipid PI(4,5)P2 (Cell, 2015). We further identify that the GARP complex is involved in cholesterol transport by targeting NPC2 to lysosomes (Cell Rep, 2017). We have reviewed the cholesterol transport at membrane contact sites (TiBS, 2018).

3. Covalent cholesterol modification of Smoothened (SMO).
Hedgehog (Hh) has been known as the only cholesterol-modified morphogen playing pivotal roles in development and tumorigenesis. A major unsolved question is how Hh signaling regulates the activity of SMO. Through an unbiased biochemical screen, we identify that SMO is covalently modified by cholesterol on the Asp95 (D95) residue through an ester bond. This modification is inhibited by Patched-1 (Ptch1) but enhanced by Hh. The cholesterylation of SMO is critical for Hh signal transduction, assuring proper embryonic development (Mol Cell, 2017). This work reveals a novel function of cholesterol as a covalent ligand of SMO to regulate cell fate.

Our long-term goal is to reveal the mechanisms of cholesterol metabolism and develop novel strategies to treat cholesterol-related diseases.


            Figure 1. Summary of Song’s work on cholesterol metabolism.

 
PUBLICATIONS (*: Corresponding author):
Representative Publications:

1) Xiao J, Luo J, Hu A, Xiao T, Li M, Kong Z, Jiang L, Zhou Z, Liao Y, Xie C, Chu B, Miao H, Li B,Shi X and
Song BL*. Cholesterol transport through the peroxisome-ER membrane contacts tethered by PI(4,5)P2 and extended synaptotagmins. Sci China Life Sci. 2019 May 22. doi:10.1007/s11427-019-9569-9. [Epub ahead of print]


2) Gong XM, Li YF, Luo J, Wang JQ, Wei J, Wang JQ, Xiao T, Xie C, Hong J, Ning G, Shi XJ, Li BL, Qi W* and Song BL*. Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance. Nature Metabolism, 1: 570-583, 2019


3) Zhang YY, Fu ZY, Wei J, Qi W, Baituola G, Luo J, Meng YJ, Guo SY, Yin H, Jiang SY, Li YF, Miao HH, Liu Y, Wang Y, Li BL, Ma YT* and Song BL*. A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science, 360(6393):1087-1092, 2018

4) Wang YJ, Bian Y, Luo J, Lu M, Xiong Y, Guo SY, Yin HY, Lin X, Li Q, Chang CCY, Chang TY, Li BL* and Song BL*. Cholesterol and fatty acids regulate cysteine ubiquitination of ACAT2 through competitive oxidation. Nature Cell Biology, 19(7): 808-819, 2017

5) Xiao X, Tang JJ, Peng C, Wang Y, Fu L, Qiu ZP, Xiong Y, Yang LF, Cui HW, He XL, Yin L, Qi W, Wong CL, Zhao Y, Li BL, Qiu WW* and Song BL*. Cholesterol modification of Smoothened is required for hedgehog signaling. Molecular Cell, 66: 154-162, 2017

6) Li N, Zhou ZS, Shen Y, Xu J, Miao HH, Xiong Y, Xu F, Li BL, Luo J and Song BL*. Inhibition of the SREBP pathway suppresses hepatocellular carcinoma through repressing inflammation. Hepatology, 65(6): 1936-1947, 2017

7) 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

8) 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  

9) 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  

10) 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

11) 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

12) 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

13) 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

14) 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

15) 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

16) 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


All Publications:

                          2019


1. Xiao J, Luo J, Hu A, Xiao T, Li M, Kong Z, Jiang L, Zhou Z, Liao Y, Xie C, Chu B, Miao H, Li B, Shi X, Song BL*. Cholesterol transport through the peroxisome-ER membrane contacts tethered by PI(4,5)P2 and extended synaptotagmins. Sci China Life Sci. 2019 May 22. doi: 10.1007/s11427-019-9569-9. [Epub ahead of print]


2. Gong XM, Li YF, Luo J, Wang JQ, Wei J, Wang JQ, Xiao T, Xie C, Hong J, Ning G, Shi XJ, Li BL, Qi W*, Song BL*. Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance. Nature Metabolism, 1: 570-583, 2019


3. Luo J, Jiang LY, Yang H, Song BL*. Intracellular cholesterol transport by sterol transfer proteins at membrane contact sites. Trends in Biochemical Sciences (Invited review), 44(3): 273-292, 2019


4. Hu A, Song BL*. The interplay of Patched, Smoothened and cholesterol in Hedgehog signaling. Curr Opin Cell Biol. 61: 31-38, 2019


5. Jiang SY, Tang JJ, Xiao X, Qi W, Wu S, Jiang C, Hong J, Xu J*, Song BL*, Luo J*. Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase. PLoS Genet. 15(7): e1008289, 2019


6. Chen L, Ma MY, Sun M, Jiang LY, Zhao XT, Fang XX, Lam SM, Shui GH, Luo J, Shi XJ, Song BL*. Endogenous sterol intermediates of the mevalonate pathway regulate HMG-CoA reductase degradation and SREBP-2 processing. J Lipid Res. 2019 Aug 27. pii: jlr.RA119000201. doi: 10.1194/jlr.RA119000201. [Epub ahead of print]


7. Han Y, Hu Z, Cui A, Liu Z, Ma F, Xue Y, Liu Y, Zhang F, Zhao Z, Yu Y, Gao J, Wei C, Li J, Fang J, Li J, Fan JG, Song BL, Li Y. Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene. Nature Communications, 10(1): 623, 2019


8. Gao M, Huang X,
Song BL, Yang H. The biogenesis of lipid droplets: Lipids take center stage. Prog Lipid Res. 75:100989, 2019 

                       2018

9. Zhang YY, Fu ZY, Wei J, Qi W, Baituola G, Luo J, Meng YJ, Guo SY, Yin H, Jiang SY, Li YF, Miao HH, Liu Y, Wang Y, Li BL, Ma YT*, Song BL*. A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science, 360(6393): 1087-1092, 2018

10. Jiang SY, Li H, Tang JJ, Wang J, Luo J, Liu B, Wang JK, Shi XJ, Cui HW, Tang J, Yang F, Qi W, Qiu WW*, Song BL*. Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol. Nature Communications, 9(1): 5138, 2018

11. Liao YC, Wei J, Wang J, Shi XJ, Luo J, Song BL*. The non-canonical NF-κB pathway promotes NPC2 expression and regulates intracellular cholesterol trafficking. Science China Life Sciences, 61(10): 1222-1232, 2018

12. Jiang LY, Jiang W, Tian N, Xiong YN, Liu J, Wei J, Wu KY, Luo J, Shi XJ*, Song BL*. Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase. Journal of Biological Chemistry, 293(11): 4047-4055, 2018  

13. Hu A, Zhao XT, Tu H, Xiao T, Fu T, Wang Y, Liu Y, Shi XJ, Luo J*, Song BL*. PIP4K2A regulates intracellular cholesterol transport through modulating PI(4,5)P2 homeostasis. Journal of Lipid Research, 59(3): 507-514, 2018

14. Guo C, Chi Z, Jiang D, Xu T, Yu W, Wang Z, Chen S, Zhang L, Liu Q, Guo X, Zhang X, Li W, Lu L, Wu Y, Song BL, Wang D*. Cholesterol homeostatic regulator SCAP-SREBP2 integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling in macrophages. Immunity, 49(5): 842-856, 2018  

                      2017

15. Wang YJ, Bian Y, Luo J, Lu M, Xiong Y, Guo SY, Yin HY, Lin X, Li Q, Chang CCY, Chang TY, Li BL*, Song BL*. Cholesterol and fatty acids regulate cysteine ubiquitination of ACAT2 through competitive oxidation. Nature Cell Biology, 19(7): 808-819, 2017  

16. Xiao X, Tang JJ, Peng C, Wang Y, Fu L, Qiu ZP, Xiong Y, Yang LF, Cui HW, He XL, Yin L, Qi W, Wong CC, Zhao Y, Li BL, Qiu WW*, Song BL*. Cholesterol modification of smoothened is required for hedgehog signaling. Molecular Cell, 66(1): 154-162, 2017  

17. Li N, Zhou ZS, Shen Y, Xu J, Miao HH, Xiong Y, Xu F, Li BL, Luo J, Song BL*. Inhibition of the SREBP pathway suppresses hepatocellular carcinoma through repressing inflammation. Hepatology, 65(6): 1936-1947, 2017  

18. Wei J, Zhang YY, Luo J, Wang JQ, Zhou YX, Miao HH, Shi XJ, Qu YX, Xu J, Li BL, Song BL*. The GARP complex is involved in intracellular cholesterol transport via targeting NPC2 to lysosomes. Cell Reports, 19(13): 2823-2835, 2017

19. Luo J, Jiang L, Yang H, Song BL*. Routes and mechanisms of post-endosomal cholesterol trafficking: a story that never ends. Traffic (Invited review), 18(4): 209-217, 2017  

20. Xie C, Gong XM, Luo J, Li BL, Song BL*. AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse Niemann-Pick type C disease. Journal of Lipid Research, 58(3): 512-518, 2017  

21. Shan B, Wang X, Wu Y, Xu C, Xia Z, Dai J, Shao M, Zhao F, He S, Yang L, Zhang M, Nan F, Li J, Liu J, Liu J, Jia W, Qiu Y, Song BL, Han JJ, Rui L, Duan SZ*, Liu Y*. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity. Nature Immunology, 18(5): 519-529, 2017  

22. Liu R, Zou Y, Hong J, Cao M, Cui B, Zhang H, Chen M, Shi J, Ning T, Zhao S, Liu W, Xiong H, Wei C, Qiu Z, Gu W, Zhang Y, Li W, Miao L, Sun Y, Yang M, Wang R, Ma Q, Xu M, Xu Y, Wang T, Chan KK, Zuo X, Chen H, Qi L, Lai S, Duan S, Song BL, Bi Y, Liu S*, Wang W*, Ning G*, Wang J*. Rare loss-of-function variants in NPC1 predispose to human obesity. Diabetes, 66(4): 935-947, 2017  

                     2016

23. Xie C, Zhang YP, Song L, Luo J, Qi W, Hu J, Lu D, Yang Z, Zhang J, Xiao J, Zhou B, Du JL, Jing N, Liu Y, Wang Y, Li BL, Song BL*, Yan Y*. Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome. Cell Research, 26(10): 1099-1111, 2016  

24. Su JF, Wei J, Li PS, Miao HH, Ma YC, Qu YX, Xu J, Qin J, Li BL, Song BL, Xu ZP*, Luo J*. Numb directs the subcellular localization of EAAT3 through binding the YxNxxF motif. Journal Cell Science, 129(16): 3104-3114, 2016  

25. Yuan Q, Fu Z, Wei J, Li PS, Miao HH, Qu YX, Xu J, Qin J, Li BL, Song BL, Ma Y*. Identification and characterization of NPC1L1 variants in Uygur and Kazakh with extreme low-density lipoprotein cholesterol. Biochemical and Biophysical Research Communications, 479(4): 628-635, 2016  

26. Ding L, Li J, Song BL, Xiao X, Zhang B, Qi M, Huang W, Yang L, Wang Z*. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Toxicology and Applied Pharmacology, 304: 99-109, 2016

27. Li J, Ding L, Song BL, Xiao X, Qi M, Yang Q, Yang Q, Tang X, Wang Z, Yang L*. Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway. European Journal of Pharmacology, 770: 99-109, 2016

28. Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, Yan C, Wang L, Chang CC, Chang TY, Zhang T, Zhou P, Song BL, Liu W, Sun SC, Liu X, Li BL*, Xu C*. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature, 531(7596): 651-655, 2016  

29. Xu D, Wang Z, Zhang Y, Jiang W, Pan Y, Song BL, Chen Y*. PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus. Nature Communications, 6: 8100, 2016  

30. Guo D, Lu M, Hu X, Xu J, Hu G, Zhu M, Zhang X, Li Q, Chang CC, Chang T, Song BL, Xiong Y, Li B*. Low-level expression of human ACAT2 gene in monocytic cells is regulated by the C/EBP transcription factors. Acta Biochimica et Biophysica Sinica, 48(11): 980-989, 2016  

31. Guo D, Zhang X, Li Q, Qian L, Xu J, Lu M, Hu X, Zhu M, Chang CC, Song BL, Chang T, Xiong Y, Li B*. The ACAT2 expression of human leukocytes is responsible for the excretion of lipoproteins containing cholesteryl/steryl esters. Acta Biochimica et Biophysica Sinica, 48(11): 990-997, 2016

                     2015

32. Chu BB, Liao YC, Qi W, Xie C, Du X, Wang J, Yang H, Miao HH, Li BL, Song BL*. Cholesterol transport through lysosome-peroxisome membrane contacts. Cell, 161(2): 291-306, 2015  

33. 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. Journal of Steroid Biochemistry and Molecular Biology, 151: 102-107, 2015

34. Xiang Y, Tang JJ, Tao W, Cao X, Song BL, Zhong J*. Identification of Cholesterol 25-Hydroxylase as a Novel Host Restriction Factor and a Part of the Primary Innate Immune Responses against Hepatitis C Virus Infection. Journal of Virology, 89(13): 6805-6816, 2015  

35. Zhu M, Zhao X, Chen J, Xu J, Hu G, Guo D, Li Q, Zhang X, Chang CC, Song BL, Xiong Y*, Chang T*, Li B*. ACAT1 regulates the dynamics of free cholesterols in plasma membrane which leads to the APP-α-processing alteration. Acta Biochimica et Biophysica Sinica, 47(12): 951-959, 2015  

36. Zhu M, Lei L, Zhu Z, Li Q, Guo D, Xu J, Chen J, Sha H, Zhang X, Yang X, Song BL, Li B*, Yan Y*, Xiong Y*. Excess TNF-α in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells. Acta Biochimica et Biophysica Sinica, 47(11): 899-907, 2015

                        2014

37. Li PS, Fu ZY, Zhang YY, Zhang JH, Xu CQ, Ma YT, Li BL, Song BL*. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nature Medicine, 20(1): 80-86. 2014  

38. 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. Journal of Biological Chemistry, 289(48): 33689-33700, 2014  

39. 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  

40. Ding L, Li J, Song BL, Xiao X, Huang W, Zhang B, Tang X, Qi M, Yang Q, Yang Q, Yang L*, Wang Z*. Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway. Journal of Pharmacology and Experimental Therapeutics, 351(2): 474-483, 2014

                     2013

41. 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. Journal of Molecular Cell Biology, 5(6): 404-415, 2013

42. 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 Research, 23(8): 1007-1024, 2013  

43. 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. Nature Communications, 4: 2005, 2013

44. Xiao X*, Song BL. SREBP: a novel therapeutic target. Acta Biochimica et Biophysica Sinica (Invited review), 45(1): 2-10, 2013  

45. Xu J, Hu G, Lu M, Xiong Y, Li Q, Chang CC, Song BL, Chang T, Li B*. MiR-9 reduces human acyl-coenzyme A: cholesterol acyltransferase-1 to decrease THP-1 macrophage-derived foam cell formation. Acta Biochimica et Biophysica Sinica, 45(11): 953-962, 2013  

                     2012

46. Liu TF, Tang JJ, Li PS, Shen Y, Li JG, Miao HH, Li BL*, Song BL*. Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis. Cell Metabolism, 16(2): 213-225, 2012  

47. Xie C, Zhou ZS, Li N, Bian Y, Wang YJ, Wang LJ, Li BL*, Song BL*. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. Journal of Lipid Research, 53(10): 2092-2101, 2012

48. Wang LJ, Song BL*. Niemann-Pick C1-Like 1 and cholesterol uptake. Biochimica et Biophysica Acta (Invited review), 1821(7): 964-972, 2012  

                     2011

49. Tang JJ, Li JG, Qi W, Qiu WW, Li PS, Li BL, Song BL*. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metabolism, 13(1): 44-56, 2011

50. Ge L, Qi W, Wang LJ, Miao HH, Qu YX, Li BL, Song BL*. Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake. Proceedings of the National Academy of Sciences of the United States of America, 108(2): 551-556, 2011  

51. 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. Journal of Biological Chemistry, 286(41): 35933-35942, 2011  

52. Zhang JH, Ge L, Qi W, Zhang L, Miao HH, Li BL, Yang M, Song BL*. The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. Journal of Biological Chemistry, 286(28): 25088-25097, 2011  

53. Wang LJ, Wang J, Li N, Ge L, Li BL, Song BL*. Molecular characterization of the NPC1L1 variants identified from cholesterol low absorbers. Journal of Biological Chemistry, 286(9): 7397-7408, 2011

                     2010

54. 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 Biochimica et Biophysica Sinica, 42(5): 303-310, 2010  

                     2009


55. Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL, Song BL*. Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. Journal of Biological Chemistry, 284(33): 22481-22490, 2009  

56. Wang J, Chu BB, Ge L, Li BL, Yan Y*, Song BL*. Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption. Journal of Lipid Research, 50(8): 1653-1662, 2009

57. Lei L, Xiong Y, Chen J, Yang JB, Wang Y, Yang XY, Chang CC, Song BL, Chang TY, Li BL*. TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation. Journal of Lipid Research, 50(6): 1057-1067, 2009  

58. Zhao XN, Chen J, Lei L, Hu GJ, Xiong Y, Xu JJ, Li Q, Yang XY, Chang C, Song BL, Chang TY, Li BL*. The optional long 5'-untranslated region of human ACAT1 mRNAs impairs the production of ACAT1 protein by promoting its mRNA decay. Acta Biochimica et Biophysica Sinica, 41: 30-41, 2009  

                     2008

59. Ge L, Wang J, Qi W, Miao HH, Cao J, Qu YX, Li BL, Song BL*. The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1. Cell Metabolism, 7(6): 508-519, 2008

60. Qi W, Song BL*. Dissecting the NPC1L1-mediated cholesterol absorption. Future Lipidology (Invited review), 3: 481-484, 2008  

61. 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 Research, 18(9): 921-936, 2008  

                     2007

62. Cao J, Wang J, Qi W, Miao HH, Wang J, Ge L, DeBose-Boyd RA, Tang JJ, Li BL*, Song BL*. Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase. Cell Metabolism, 6(2): 115-128, 2007  

                     2002-2005

63. Song BL, Sever N, 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  

64. Song BL, Javitt NB, DeBose-Boyd RA*. Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol. Cell Metabolism, 1(3): 179-189, 2005

65. Song BL*, DeBose-Boyd RA*. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. Journal of Biological Chemistry, 281(35): 25054-25061, 2006

66. Song BL, 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. Journal of Biological Chemistry, 279(27): 28798-28806, 2004  

67. Sever N#, Song BL#, Yabe D#, Goldstein JL, Brown MS, DeBose-Boyd RA*. Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol. Journal of Biological Chemistry, 278(52): 52479-52490, 2003  

68. Lee JN, Song BL, DeBose-Boyd RA, Ye J*. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. Journal of Biological Chemistry, 281(51): 39308-15, 2006

69. Sever N, Lee PC, Song BL, Rawson RB, 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. Journal of Biological Chemistry, 279(41): 43136-43147, 2004



伟德官网宋保亮教授实验室博士后招聘信息(2018年4月27日)


             

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