林树海 LIN Shu-Hai, Ph.D.

教授

代谢组学与细胞代谢（Metabolomics and Cellular Metabolism）

课题组长

E-mail：shuhai@xmu.edu.cn

2003年，广州中医药大学中药学院，学士；

2005年，中山大学药学院，硕士；

2006-2007年，康化（上海）新药研发有限公司；

2011年，香港浸会大学化学系，博士；

2011-2012年，香港浸会大学化学系，博士后；

2012-2014年，香港浸会大学化学系，研究助理教授；

2014-2015年，香港浸会大学中医药学院，高级研究员；

2015年12月-2018年1月，上海交通大学医学院基础医学院副研究员、研究员；

2018年2月-8月，上海交通大学附属第六人民医院转化医学中心，研究员；

2018年10至今，厦门大学生命科学学院，教授。

2003, BSc, College of Chinese Medicine, Guangzhou University of Chinese Medicine;

2005, MSc, School of Pharmaceutical Sciences, Sun Yat-sen University;

2006-2007, PepTech (Shanghai) Pharmaceutical Co., Ltd;

2011, Ph. D., Department of Chemistry, Hong Kong Baptist University;

2011-2012, Postdoctoral Fellow, Department of Chemistry, Hong Kong Baptist University;

2012-2014, Research Assistant Professor, Department of Chemistry, Hong Kong Baptist University;

2014-2015, Senior Research Associate, School of Chinese Medicine, Hong Kong Baptist University;

Dec. 2015-Jan. 2018, Associate Professor, Professor, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine;

Feb. 2018-Aug. 2018, Professor, Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital;

Oct. 2018- Professor, School of Life Sciences, Xiamen University.

研究领域(Research Area)

代谢组学：运用先进质谱技术和稳定同位素标记（13C, 15N, 2H）原子在示踪分子（Tracer）的位置不同，用以描述特定代谢通路。基于质量同位素体分布，开发数学模型描述细胞中代谢通路的活性与动态变化，开展体内外代谢流的定量分析。体内代谢流分析，重点关注不同组织与循环系统之间的代谢对话；体外代谢流分析，重点关注免疫细胞与其他细胞之间的代谢通讯和亚细胞水平的代谢穿梭，比如苹果酸-天冬氨酸穿梭，柠檬酸-丙酮酸穿梭和磷酸甘油穿梭。

细胞代谢：过去的肿瘤代谢研究中，普遍忽略微环境对肿瘤代谢的影响。本课题组将运用体内外代谢流分析技术，结合生物化学和遗传学等技术手段，定量解释环境因素对肿瘤代谢重编程的影响。特别是通过开发先进质谱技术方法，与肿瘤生物学家、免疫学家合作，更好地理解免疫代谢如何在肿瘤微环境中精确调节。从代谢生物学研究中的物质与能量分配问题到精准医学中的临床队列代谢组学分析，都是本课题感兴趣的研究领域。

Research Area

Metabolomics: By employing state-of-the-art mass spectrometry and stable isotope (13C, 15N, 2H) atoms in the tracer molecules, we analyze the specific metabolic pathways. Based on mass isotopologue distribution, we will establish mathematical modeling to delineate the activity and dynamic changes of metabolic pathways for metabolic flux analysis in in vivo and vitro. In vivo, we mainly focus on metabolic cross-talks between tissues and circulation system; in vitro, we mainly focus on metabolic communications between immune cells and other types of cells as well as metabolic shuttling at subcellular level, such as malate-aspartate shuttle, citrate-pyruvate shuttle and glycerophosphate shuttle.

Cellular metabolism: In the past decades, the impacts of microenvironment on cancer metabolism are largely overlooked. By applying metabolic flux analysis in vivo, in combination with biochemistry and genetics, we will quantitatively explain the impact of environmental factors on metabolic reprogramming in tumors. In particular, we are developing novel mass spectrometric technologies and collaborating with oncologists and immunologists for a better understanding of precision modulation of immunometabolism within the tumor microenvironment. We are also interested in the research fields ranging from distribution of nutrient utilization and energy expenditure in metabolic biology to metabolomics of clinical cohorts in precision medicine.

代表性论文(Selected Publications)

[1] Cao Y#, Lin SH#, Wang Y, Chin YE, Kang L, Mi J. Glutamic pyruvate transaminase GPT2 promotes tumorigenesis of breast cancer cells by activating sonic hedgehog signaling. Theranostics. 2017; 7(12): 3021-3033.

[2] Chen GQ, Gong RH, Yang DJ, Zhang G, Lu AP, Yan SC, Lin SH*, Bian ZX*. Halofuginone Dually Regulates Autophagic Flux through Nutrient-Sensing Pathways in Colorectal Cancer. Cell Death Dis., 2017; 8(5):e2789.

[3] Cao TT#, Lin SH#, Fu L#, Tang Z, Che CM, Zhang LY, Ming XY, Liu TF, Tang XM, Tan BB, Xiang D, Li F, Chan OY, Xie D, Cai Z, Guan XY. Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in hepatocellular carcinoma cells. Carcinogenesis. 2017;38(1):94-104.

[4] Gao X#, Lin SH#, Ren F, Li JT, Chen JJ, Yao CB, Yang HB, Jiang SX, Yan GQ, Wang D, Wang Y, Liu Y, Cai Z, Xu YY, Chen J, Yu W, Yang PY, Lei QY. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat Commun. 2016; 7:11960.

[5] Lin SH#, Liu T#, Ming X, Tang Z, Fu L, Schmitt-Kopplin P, Kanawati B, Guan XY, Cai Z. Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions. Sci. Rep. 2016; 6:21184.

[6] Chen GQ, Tang CF, Shi XK, Lin CY, Fatima S, Pan XH, Yang DJ, Zhang G, Lu AP, Lin SH*, Bian ZX*. Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism. Oncotarget. 2015; 6(27):24148-62.

[7] Tang Z, Li S, Guan X, Schmitt-Kopplin P, Lin S*, Cai Z*. Rapid assessment of coenzyme Q10 redox state using ultrahigh performance liquid chromatography tandem mass spectrometry. Analyst. 2014; 139(21):5600-4.

[8] Lin S#, Kanawati B#, Liu L, Witting M, Li M, Huang J, Schmitt-Kopplin P, Cai Z. Ultrahigh resolution mass spectrometry-based metabolic characterization reveals cerebellum as a disturbed region in two animal models. Talanta. 2014; 118(1), 45-53.

[9] Lin S, Liu H, Kanawati B, Liu L, Dong J, Li M, Huang J, Schmitt-Kopplin P, Cai Z. Hippocampal metabolomics using ultrahigh-resolution mass spectrometry reveals neuroinflammation from Alzheimer's disease in CRND8 mice. Anal. Bioanal. Chem. 2013; 405(15):5105-17.

[10] Lin S, Yang Z, Liu H, Tang L, Cai Z. Beyond glucose: Metabolic shifts in responses to the effects of the oral glucose tolerance test and the high-fructose diet in rats. Mol. Biosyst. 2011; 7(5):1537-48. 

[11] Lin S, Yang Z, Liu H, Cai Z. Metabolomic Analysis of Liver and Skeletal Muscle Tissues in C57BL/6J and DBA/2J Mice Exposed to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. Mol. Biosyst.2011; 7(6): 1956-65.

[12] Lin S, Yang Z, Zhang X, Bian Z, Cai Z. Hippocampal Metabolomics Reveals 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Toxicity Associated with Ageing in Sprague-Dawley Rats. Talanta, 2011; 85(2): 1007-12.

[13] Lin S, Chan W, and Cai Z. Liquid chromatography/mass spectrometry for investigating the biochemical effects induced by aristolochic acid in rats: the plasma metabolome. Rapid Commnun. Mass Spectrom. 2010; 24(9): 1312-8.

[14] Lin S, Liu N, Yang Z, Song W, Wang P, Chen H, Lucio M, Schmitt-Kopplin P, Chen G, Cai Z. GC/MS-based metabolomics reveals fatty acid biosynthesis and cholesterol metabolism in cell lines infected with influenza A virus. Talanta. 2010; 83(1):262-8.

[15] Lin S, Wang D, Yang D, Yao J, Tong Y, Chen J. Characterization of steroidal saponins in crude extract from Dioscoreanipponica Makino by liquid chromatography tandem multi-stage mass spectrometry. Anal Chim Acta. 2007; 599(1): 98-106.