李蓬
李蓬主要成就
科研综述李蓬发现细胞内调节脂代谢的细胞器脂滴可通过特殊的融合方式而生长，在脂代谢调控中起重要作用；发现和鉴定了多个与脂滴融合相关的重要蛋白和调控因子，系统阐明了脂滴融合的生物化学和细胞生物学机制；运用小鼠模型和临床样品等从生理和病理机制上证明脂滴融合是肥胖和非酒精性脂肪肝发生的细胞生物学基础，分析鉴定了调控肝脏细胞，乳腺表皮细胞，皮脂细胞中脂肪分泌的重要通路及其调控机制；从生物化学，细胞生物学，生理学和病理学等多个角度阐明了脂代谢调控的机制和代谢性疾病发生和发展的基础。学术论著截至2017年，李蓬在国际顶尖杂志如Cell、Nature、Nature Cell Biology、Genes & Development等发表70余篇具有较高影响因子的国际论文，代表论文如下：Du X#, Zhou L#, Aw Y, Mak HY, Xu Y, Rae J, Wang W, Zadoorian A, Hancock S, Osborne B, Chen X, Wu JW, Turner N, Parton RG, Li P*, Yang H*. ORP5 localizes to ER-lipid droplet contacts and regulates the level of PI(4)P on lipid droplets. J Cell Biol, 2020, 219(1): e201905162.Chen FJ, Yin Y, Chua BT, Li P*. CIDE family proteins control lipid homeostasis and the development of metabolic diseases. Traffic, 2020,21(1): 94-105.Lv X#, Liu J#, Qin Y, Liu Y, Jin M, Dai J, Chua BT, Yang H, Li P*. Identification of gene products that control lipid droplet size in yeast using a high-throughput quantitative image analysis. Biochim Biophys Acta Mol Cell Biol Lipids, 2019, 1864(2): 113-127.Li Q, Zhao Q, Zhang J, Zhou L, Zhang W, Chua B, Chen Y, Xu L*, Li P*. The Protein Phosphatase 1 Complex Is a Direct Target of AKT that Links Insulin Signaling to Hepatic Glycogen Deposition. Cell Rep, 2019, 28(13): 3406-3422.Su L#, Zhou L#, Chen FJ, Wang H, Qian H, Sheng Y, Zhu Y, Yu H, Gong X, Cai L, Yang X, Xu L, Zhao TJ, Li JZ, Chen X*, Li P*. Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites. EMBO J, 2019, 38(8): e100156.Wang J, Yan C, Xu C, Chua BT, Li P*, Chen FJ*. Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids. J Biol Chem, 2018, 293(50): 19330-19343.Zhou L#, Yu M#, Arshad M, Wang W, Lu Y, Gong J, Gu Y, Li P*, Xu L*. Coordination Among Lipid Droplets, Peroxisomes, and Mitochondria Regulates Energy Expenditure Through the CIDE-ATGL-PPARα Pathway in Adipocytes. Diabetes, 2018, 67(10): 1935-1948.Xu D#, Li Y#, Wu L#, Li Y, Zhao D, Yu J, Huang T, Ferguson C, Parton RG, Yang H, Li P*. Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions. J Cell Biol, 2018: 975-995.Qian H, Chen Y, Nian Z, Su L, Yu H, Chen FJ, Zhang X, Xu W, Zhou L, Liu J, Yu J, Yu L, Gao Y, Zhang H, Zhang H, Zhao S, Yu L, Xiao RP, Bao Y, Hou S, Li P, Li J, Deng H, Jia W, Li P*. HDAC6-mediated acetylation of lipid droplet-binding protein CIDEC regulates fat-induced lipid storage. J Clin Invest, 2017, 127: 1353-1369.Zhou L, Park SY, Xu L, Xia X, Ye J, Su L, Jeong KH, Hur JH2, Oh H, Tamori Y, Zingaretti CM, Cinti S, Argente J, Yu M, Wu L, Ju S, Guan F,Yang H, Choi CS, Savage DB, Li P*. Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27 deficient mice. Nat Commum, 2015, 6: 5949.Wu L, Xu D, Zhou L, Xie B, Yu L, Yang H, Huang L, Ye J, Deng H, Yuan YA, Chen S, Li P*. Rab8a-AS160-MSS4 regulatory circuit controls lipid droplet fusion and growth. Dev Cell, 2014, 30: 378-393.Zhang S, Shui G, Wang G, Wang C, Sun S, Zouboulis CC, Xiao R, Ye J, Li W, Li P*. Cidea control of lipid storage and secretion in mouse and human sebaceous Glands, Mol Cell Biol, 2014, 34: 1827-1838.Sun Z, Gong J, Wu H, Xu W, Wu L, Xu D, Gao J, Wu J, Yang H, Yang M and Li P*. Perilipin1 promotes unilocular lipid droplet formation through activation of Fsp27 in adipocytes. Nat Commum, 2013, 4: 1594.Xu L, Zhou L, Li P*. CIDE proteins and lipid metabolism. Arterioscler Thromb Vasc Biol, 2012, 32: 1094-1098.Zhou L, Xu L, Ye J, Li D, Wang W, Li X, Wu L, Wang H, Guan F, Li P*. Cidea promotes hepatic steatosis by sensing dietary fatty acids. Hepatology, 2012, 56: 95-107.Wang W, Lv N, Zhang S, Shui G, Qian H, Zhang J, Chen Y, Ye J, Xie Y, Shen Y, Wenk MR, Li P*. Cidea is an essential transcriptional coactivator regulating mammary gland secretion of milk lipids. Nat Med, 2012, 18: 235-243.Gong J, Sun Z, Wu L, Xu W, Schieber N, Xu D, Shui G, Yang H, Parton RG, Li P*. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J Cell Biol, 2011, 195: 953-963.Ye J, Li JZ, Liu Y, Li X, Yang T, Ma X, Li Q, Yao Z, Li P*. Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab, 2009, 9: 177-190.Qi J, Gong J, Zhao T, Zhao J, Lam P, Ye J, Li JZ, Wu J, Zhou HM, Li P*. Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. EMBO J, 2008, 27: 1537-1548.Li JZ, Ye J, Xue B, Qi J, Zhang J, Zhou Z, Li Q, Wen Z, Li P*. Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes, 2007, 56: 2523-2532.Zhou Z, Yon Toh S, Chen Z, Guo K, Ng CP, Ponniah S, Lin SC, Hong W, Li P*. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat Genetics, 2003, 35: 49-56.Chua BT, Volbracht C, Ta KOn, Li R, Yu V and Li P*. Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat Cell Biol, 2003, 5: 1083-1089.Li P, Nijhawan D, Budihardio I, Srinivasula SM, Ahmad M, Alnemri ES, and Wang X. Cytochrome C and dATP-dependent formation of Apaf-1/Caspase-9 complex initiates an apoptotic protease cascade. Cell, 1997, 91: 478-489.Li P, Yang X, Wasser M, Cai Y, Chia W. Inscuteable and Staufen mediate asymmetric localization and segregation for Prospero RNA during Drosophila neuroblast cell divisions. Cell, 1997, 90: 437-447.团队建设李蓬承担很多的科研管理、学科规划、平台搭建和制度建设工作，她带领的课题组每周六上午开组会，只要时间允许，她一定出席。2005年回国来到清华搭建自己的研究平台，经历了两三年的磨合，搭平台、买设施、建文化，而且要手把手地带出一批研究生出来，直到第一拨学生真正在知识和技术上培养出来，课题组在2007年才有第一篇论文，从这之后李蓬课题组成果不断，取得了一系列具有原创性、系统性和连续性的成果，研究工作处于国际脂代谢领域的前沿。她除了承担多门课程，还负责清华大学生命科学学院的科研平台建设和人才引进。教育思想李蓬认为学生们都很聪明，也很认真，但思想容易波动，尤其是实验遇到挫折时，会产生焦虑甚至动摇做科学的决心。科研应先不谈结果，要坚持下去不怕失败，山穷水尽疑无路，柳暗花明又一村，有可能下一个实验就会带来一片新天地。科研最需要的是无畏的精神，希望清华的学生们能真正从事国际上最顶尖的科学研究。
