研究方向

1. 脂滴生物学

脂滴是重要的细胞器，存在于所有真核生物中。脂滴与其它细胞器互作，响应胞内外环境变化，动态调节细胞的脂类代谢和能量平衡，参与生物体的生长、发育、生殖、衰老、抗逆境等。脂滴在脂肪组织和非脂肪组织（如肝脏）中大量沉积，导致肥胖、脂肪肝、糖尿病等代谢性疾病。我们利用秀丽线虫和小鼠等模式生物，结合细胞生物学、遗传学、生物化学及分子生物学，以及脂质代谢流、分子影像等方法和技术，重点研究：1）脂肪酸的合成、调控及其生物学功能；2）脂滴起源、增大和融合的分子机理；3）不同生理或病理条件下脂滴与其它细胞器互作维持细胞和机体能量平衡机理；进而揭示脂代谢紊乱相关疾病如脂肪肝和糖尿病等代谢性疾病的发病机理，寻找新的疾病标志物和治疗靶标。

2. 脂肪肝发病机理及治疗

肝脏是重要的代谢器官。临床上，当肝脏中多于5%的肝细胞出现脂滴积累时，即为肝脏脂肪变性。随着肝脏中脂肪过多的积累，脂毒性、胰岛素抵抗等多种因素作用下，出现小叶炎症和肝细胞损伤等，肝脏脂肪变性发展为脂肪性肝炎；如果脂肪性肝炎中出现胶原沉积则发展形成肝脏纤维化，继续恶化则导致肝硬化和肝癌。

我们建立了脂肪肝细胞、小鼠、树鼩和猕猴模型。发现树鼩是一种新型的非肥胖型脂肪肝（non-obese fatty liver）动物模型；筛选到一些自发性肥胖、脂肪肝和糖尿病猕猴。基于上述脂肪肝细胞和动物模型，利用转录组、蛋白质组、代谢组等，开展脂肪肝的发病机理研究，寻找新的疾病标志物和治疗靶标；同时开展减肥降脂药物的筛选、评价和作用机理研究。我们新发现一个脂肪肝致病因子——钙结合蛋白S100A11，其表达和脂肪肝的进展正相关，S100A11过表达通过HDAC6-FOXO1轴上调自噬和脂肪合成，导致脂肪肝（Zhang, et al. CMGH，2020）。目前正在研究S100A11在肝脏及其它代谢性疾病中的作用机理。

正在承担的科研项目

1. 云南省科技厅—云南大学联合基金（双一流重点项目），“钙结合蛋白 S100A11 在肝纤维化中的作用及调控机理”，2019FY003021，项目负责人，2019/ 9/1-2022/8/31。

2. 科技部国家重点研发计划重点专项，“应激对组织器官代谢稳态和发育的调控作用与机制”，课题三“应激调控细胞器稳态的代谢效应与机制”，2018YPA0800703，课题负责人，2019/07-2024/06。

3. 国家自然科学基金“重大研究计划”培育项目，91857113，“LET-767参与胰岛素信号通路调控脂代谢的分子机理研究”，2019/01—2021/12，项目负责人。

4. 国家自然科学基金－云南省联合基金（重点项目），U1702288，“树鼩肝脏脂肪储存方式与非肥胖型脂肪肝发病机制研究”，2018/01—2021/12，项目负责人。

获奖情况：

2018年  陈策实、梁斌、夏侯军，“乳腺癌及代谢性疾病树鼩模型的创建与研究”，云南省自然科学奖三等奖。

发表研究论文（#通讯作者；*共同第一作者. 按发表年代排序):

1. Yan-Hu Liu*, Lu Wang*, Zhiguo Zhang*, Newton O. Otecko, Saber Khederzadeh, Yongqin Dai, Bin Liang#, Guo-Dong Wang#, Ya-Ping Zhang#. Whole-genome sequencing reveals lactase persistence adaptation in European dogs. Molecular Biology and Evolution. In press.

2. Fan Q, Xu F#, Liang B# and Zou X#. The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism. Front. Pharmacol. (2021) doi: 10.3389/fphar.2021.696603.

3. Zhang L*, Zhu T*, Miao H# and Liang B#. The Calcium Binding Protein S100A11 and Its Roles in Diseases. Front. Cell Dev. Biol. (2021) doi: 10.3389/fcell.2021.693262.

4. Lou P*, Bi X*, Tian Y*, Li G, Kang Q, Lv C, Song Y, Xu J, Sheng X, Yang X, Liu R, Meng Q, Ren F, Plikus MV, Liang B, Zhang B#, Guo H#, Yu Z#. MiR-22 modulates brown adipocyte thermogenesis by synergistically activating the glycolytic and mTORC1 signaling pathways. Theranostics (2021). doi:10.7150/thno.50900.

5. Linqiang Zhang*, Zhiguo Zhang*, Chengbin Li*, Tingting Zhu, Jing Gao, Hu Zhou, Yingzhuan Zheng, Qing Chang, Mingshan Wang, Jieyu Wu, Liyuan Ran, Yingjie Wu#, Huilai Miao#, Xiaoju Zou#, and Bin Liang#. S100A11 promotes liver steatosis via FOXO1 mediated autophagy and lipogenesis. Cellular and Molecular Gastroenterology and Hepatology (2020). doi.org/10.1016/j.jcmgh.2020.10.006.

6. Jian-Wei Hao, Juan Wang, Huiling Guo, Yin-Yue Zhao, Hui-Hui Sun, Yi-Fan Li, Xiao-Ying Lai, Ning Zhao, Xu Wang, Changchuan Xie, Lixin Hong, Xi Huang, Hong-Rui Wang, Cheng-Bin Li, Bin Liang, Shuai Chen#, and Tong-Jin Zhao#. CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis. Nature Communications (2020). doi.org/10.1038/s41467-020-18565-8.

7. Liu X, Liu B, Li R, Wang F, Wang N, Zhang M, Bai Y, Wu J, Liu L, Han D, Li Z, Feng B, Zhou G, Wang S, Zeng L, Miao J, Yao Y, Liang B, Huang L#, Wang Q#, and Wu Y#.  miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6. Front. Cell Dev. Biol. (2020) doi:10.3389/fcell.2020.00847

8. Liujuan Cui, Mirza Ahmed Hammad, Shuyan Zhang, Bin Liang, and Pingsheng Liu#. Lipid Droplets and Mitochondria Are Anchored during Brown Adipocyte Differentiation. Protein & Cell. (2019). doi.org/10.1007/s13238-019-00661-1.

9. Yong Shao*, Hang-Yu Tian*, Jing-Jing Zhang*, Hamed Kharrati-Koopaee*, Xing Guo, Xiao-Lin Zhuang, Ming-Li Li, Hojjat Asadollahpour Nanaie, Elahe Dehghani Tafti, Bahador Shojaei, Mohammad Reza Namavar, Narges Sotoudeh, Adeola Oluwakemi Ayoola, Jia-Li Li, Bin Liang#, Ali Esmailizadeh#, Shu Wang#, & Dong-Dong Wu#. Genomic and phenotypic analyses reveal mechanisms underlying homing ability in pigeon. Molecular Biology and Evolution. (2019). doi.org/10.1093/molbev/msz208.

10. Shuang Wang*, Ning Wang*, Bin Yu, Mingxing Cao, Yanlong Wang, Yuqi Guo, Yanli Zhang, Ping Zhang, Bin Liang#, Xin Li# and Yingjie Wu#. Circulating IGF-1 Promotes Prostate Adenocarcinoma via FOXO3A/BIM Signaling in a Double Transgenic Mouse Model. Oncogene. (2019). doi: 10.1038/s41388-019-0880-9.

11. Ran, L. *, Wang, X., Mi*, A., Liu, Y., Wu, J., Wang, H., Guo, M., Sun, J., Liu, B., Li, Y., Wang, D., Jiang, R., Wang, N., Gao, W., Zeng, L., Huang, L., Chen, X., LeRoith, D., Liang, B. #, Li, X. #, Wu, Y#., Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis, iScience (2019),  doi.org/10.1016/j.isci.2019.05.020.

12. Mengqiao Cui, Rong Ying, Xue Jiang, Gang Li, Xuanjun Zhang, Jun Zheng, Kin Yip Tam, Bin Liang, Anbing Shi, Verena Gobel#, and Hongjie Zhang#. A model of hereditary sensory and autonomic neuropathy type 1 reveals a role of glycosphingolipids in neuronal polarity. Journal of Neuroscience. (2019). doi.org/10.1523/JNEUROSCI.2541-18.2019.

13. Shimeng Xu*, Fei Zou*, Zhiqing Diao^*, Shuyan Zhang, Yaqin Deng, Xiaotong Zhu, Liujuan Cui, Jinhai Yu, Zhiguang Zhang, Adekunle Toyin Bamigbade, Hongchao Zhang, Xuan Wei, Xuelin Zhang, Bin Liang#, and Pingsheng Liu#. Perilipin 2 and lipid droplets provide reciprocal stabilization. Biophysics Reports. (2019). doi.org/10.1007/s41048-019-0091-5.

14. Junlong Wang*, Linqiang Zhang*, Ruyue Xiao, Yunhai Li, Shasha Liao, Zhiguo Zhang, Wenhui Yang, Bin Liang^#. Plasma lipidomic signatures of spontaneous obese rhesus monkeys. Lipids in Health and Disease. (2019). doi.org/10.1186/ s12944-018-0952-9.

15. Jieyu Wu ^*, Xue Jiang^*, Yamei Li, Tingting Zhu, Jingjing Zhang, Zhiguo Zhang, Lingqiang Zhang , Yuru Zhang , Yanli Wang, Xiaoju Zou^#, Bin Liang#. PHA-4/FoxA senses nucleolar stress to regulate lipid accumulation in Caenorhabditis elegans. Nature Communications. (2018) doi.org/10.1038/s41467-018-03531-2.

16. Jinhai Yu*, Linqiang Zhang*, Yunhai Li, Xiaotong Zhu, Shimeng Xu, Xiao-Ming Zhou, Haizhen Wang, Hongchao Zhang, Bin Liang#, and Pingsheng Liu^#. The Adrenal Lipid Droplet is a New Site for Steroid Hormone Metabolism. Proteomics. (2018). DOI: 10.1002/pmic.20180013（封面文章）

17. Junlong Wang^*, Shimeng Xu^*, Jing Gao^*, Linqiang Zhang, Zhiguo Zhang, Wenhui Yang, Hu Zhou^#, Pingsheng Liu^#, and Bin Liang#. SILAC-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys. Am J Physiol Endocrinol Metab. (2018). doi.org/10.1152/ajpendo.00016.2018.

18. Baoshen He*, Jingjing Zhang*, Yanli Wang, Yamei Li, Xiaoju Zou^#, Bin Liang#. Identification of cytochrome b5 CYTB-5.1 and CYTB-5.2 in C. elegans; evidence for differential regulation of SCD. BBA-Mol Cell Biol Lipids. (2018). doi: 10.1016/j.bbalip.2017.12.007.

19. Zhang JJ, Hao JJ, Zhang YR, Wang YL, Li MY, Miao HL, Zou XJ^#, Liang B#. Zinc Mediates the SREBP-SCD Axis to Regulate Lipid Metabolism in Caenorhabditis elegans. Journal of Lipid Research. (2017). doi:10.1194/jlr.M077198（封面文章）

20. Yanli Wang*, Cangsang Xie*, Zhiqing Diao and Bin Liang#. Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans. Molecules. (2017). doi:10.3390. 

21. Haizhen Wang*, Xue Jiang*, Jieyu Wu, Linqiang Zhang, Jingfei Huang, Yuru Zhang, Xiaoju Zou^#, Bin Liang#. Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans. Genetics. (2016). doi: 10.1534/genetics.116. 186742  (Comments by GENES to GENOMES https://genestogenomes.org/how-worms-that-pump-iron-get-fat/)

22. Linqiang Zhang*, Xiaoyun Wu*, Shasha Liao*, Yunhai Li, Zhiguo Zhang, Qing Chang, Ruyue Xiao, and Bin Liang#. Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease. Biology Open. (2016). doi:10.1242/bio.020875.

23. Yuru Zhang*, Haizhen Wang* , Jingjing Zhang* ,Ying Hu*, Linqiang Zhang, Xiaoyun Wu, Xiong Su, Tingting Li, Xiaoju Zou^#, Bin Liang#. Cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans. BBA- Mol Cell Biol Lipids. (2016). doi:10.1016/j.bbalip. 2016.01.009.

24. Xiao, R.-Y.; Hao, J.; Ding, Y.-H.; Che, Y.-Y.; Zou, X.-J^#.; Liang, B#. Transcriptome Profile Reveals that Pu-Erh Tea Represses the Expression of Vitellogenin Family to Reduce Fat Accumulation in Caenorhabditis elegans. Molecules. (2016). doi:10.3390.

25. Xiaoyun Wu*, Haibo Xu*, Zhiguo Zhang, Qing Chang, Shasha Liao, Linqiang Zhang, Yunhai Li, Dongdong Wu^# and Bin Liang#. Transcriptome profiles using next generation sequencing reveal liver changes in the early stage of diabetes in tree shrew (Tupaia belangeri chinensis). Journal of Diabetes Research. (2016). doi:10.1155/2016/6238526

26. Linqiang Zhang*, Zhiguo Zhang*, Yunhai Li*, Shasha Liao, Xiaoyun Wu, Qing Chang & Bin Liang#. Cholesterol induces lipoprotein lipase expression in a tree shrew (Tupaia belangeri chinensis) model of non-alcoholic fatty liver disease. Scientific. Reports. (2015). doi:10.1038/srep15970.

27. YiHong Ding*, XiaoJu Zou^#*, Xue Jiang, JieYu Wu, YuRu Zhang, Dan Chen, Bin Liang#. Pu-Erh Tea Down-Regulates Sterol Regulatory Element-Binding Protein and Stearyol-CoA Desaturase to Reduce Fat Storage in Caenorhaditis elegans. PLoS ONE (2015). doi:10.1371/journal.pone.0113815. 

28. Shi X*, Li J*, Zou X, Greggain J, Rodkaer SV, Faergeman NJ, Liang B#, Watts JL^#. Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase. Journal of Lipid Research. (2013). 2504–2514.

29. Yuru Zhang, Xiaoju zou, Yihong Ding, Haizhen Wang, Xiaoyun Wu, Bin Liang#. Comparative Genomics and Functional Study of Lipid Metabolic Genes in Caenorhabditis elegans. BMC Genomics. (2013). doi:10.1186/1471-2164-14-164. (Highly accessed) 

30. Wu X*, Zou X*, Chang Q, Zhang Y, Li Y, Zhang L, Huang J, Liang B#. The Evolutionary Pattern and the Regulation of Stearoyl-CoA Desaturase Genes. BioMed Research International. (2013). doi:10.1155/2013/856521.

31. X. Wu*, Q. Chang*, Y. Zhang*, X. Zou, L. Chen, L. Zhang, L. Lv，and B. Liang#.  Relationships between body weight, fasting blood glucose, sex and age in tree shrews (Tupaia belangeri chinensis). J Anim Physiol Anim Nutr. (2013). doi: 10.1111/jpn.12036.

32. Yu Fan, Zhi-Yong Huang, Chang-Chang Cao, Ce-Shi Chen, Yuan-Xin Chen, Ding-Ding Fan, Jing He, Hao-Long Hou, Li Hu, Xin-Tian Hu, Xuan-Ting Jiang, Ren Lai,Yong-Shan Lang, Bin Liang, Sheng-Guang Liao, Dan Mu, Yuan-Ye Ma, Yu-Yu Niu, Xiao-Qing Sun, Jin-Quan Xia, Jin Xiao, Zhi-Qiang Xiong, Lin Xu, Lan Yang, Yun Zhang, Wei Zhao, Xu-Dong Zhao, Yong-Tang Zheng, Ju-Min Zhou, Ya-Bing Zhu, Guo-Jie Zhang, Jun Wang & Yong-Gang Yao. Genome of the Chinese Tree Shrew. Nature Communications (2013). doi: 10.1038 /ncomms2416.

33. Rong-Xia Li, Wei Xu, Zhen Wang, Bin Liang, Jia-Rui Wu, Rong Zeng. Proteomic characteristics of liver and muscle of Chinese tree shrew (Tupaia belangeri chinensis). Protein & Cell. (2012). 3(9): 691-700.

34. Gholamali Jafari*, Yusu Xie*, Andrey Kullyev, Bin Liang, and Ji Ying Sze. Regulation of extra-synaptic 5-HT by SERT function in 5-HT-absorbing neurons underscores adaptation behavior in C. elegans. Journal of Neuroscience, (2011).31(24):8948-8957.

35. Bin Liang, Kim Ferguson, Lisa Kadyk, and Jennifer L. Watts. The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One, (2010) 5(3) e9869.

36. Kyleann K. Brooks, Bin Liang, Jennifer L. Watts. The influence of bacterial diet on fat storage in C. elegans. PLoS One, (2009) 4(10) e7545.

37. Bin Liang, Mustapha Moussaif, Chih-Jen Kuan, J. Jay Gargus and Ji Ying Sze. Serotonin targets the DAF-16/FOXO signaling pathway to modulate stress responses. Cell Metabolism, (2006) Dec;4(6):429-440. (Preview in Cell Metabolism, 2006 Dec; 4(6):415-417.)

工作单位：云南大学生命科学学院/生命科学中心

Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming 650091, China.

单位地址：昆明市呈贡区大学城东外环南路

邮    编：650500

电子邮箱：liangb73#ynu.edu.cn