迟连利 教授 博士生导师
山东省青岛市即墨区滨海路72号山东大学青岛校区淦昌苑F楼130室
邮编:266237
电话:0532-58631419
Email:lianlichi@sdu.edu.cn
教育经历
1995年-1999年在中国海洋大学食品科学与工程本科专业学习,获理学学士学位;
1999年-2002年在中国海洋大学食品与药物研究所攻读硕士研究生,获工学硕士学位;
2002年进入美国University of Iowa药学专业攻读博士学位,2003年随导师转入Rensselaer Polytechnic Institute化学与化学生物系分析化学专业,2006年12月获博士学位。
工作经历
2005年曾在美国新泽西葛兰素史克公司(GlaxoSmithKline)担任实习顾问,参与戒烟药的研发。
2007年起在美国芝加哥雅培公司(Abbott Laboratories)担任资深科学家,主要从事疾病相关蛋白和糖链标志物的研究,参与了生殖细胞癌hCG、急性肾损伤NGAL、心血管疾病PlGF和丙肝HCV等诊断产品的研发。
2010年被山东大学国家糖工程技术研究中心聘为教授、博士生导师,主要从事生物质谱新方法开发、低分子肝素等生化药物结构确证以及糖缀合物参与疾病发生发展机制等方面的研究。已发表SCI收录论文60余篇,授权国际发明专利3项,国家发明专利11项。
研究方向
1、生物质谱技术研究多糖和蛋白的结构与功能。
2、重大疾病的蛋白组学和糖组学;诊断标志物及新药靶点研究。
3、蛋白药物、糖药物和中药的应用开发研究。
学术荣誉
第二届“张树政糖科学奖”优秀青年奖(2017年),第1位。
首届“张天民糖类药物”杰出青年奖(2020年),第1位。
多组学技术在代谢疾病机制及生物大分子功能结构表征研究中的应用,山东省科技进步二等奖(2019年),第3位。
肝素类药物质量安全控制关键技术创新及应用,山东省药学会科学技术奖一等奖(2020年),第3位。
主持项目
国家自然科学基金面上项目“低分子肝素糖链的结构细分及抗动脉粥样硬化机制研究” (21877072),2019年-2022年;
国家自然科学基金面上项目“糖胺聚糖的序列及其与肿瘤蛋白的相互作用位点研究”(21472115),2015年-2018年;
国家自然科学基金青年基金“癌症生物标志物糖基化及影响抗体亲和的质谱研究”(31000367),2011年-2013年;
教育部博士点基金“糖链结构信息库和糖链质谱数据库的构建”(20100131120071),2011年-2013年;
山东省自然科学基金“肝素糖链的精细结构及其抗动脉粥样硬化的分子机制”(ZR2019MB014),2019年-2022年;
山东省自然科学基金“肝素多糖结构的质谱分析研究”(ZR2010CM041),2010年-2013年;
多家生物医药企业委托技术开发课题50余项。
参与项目
国家重点研发计划“新兴生物功能性物质结构关键计量技术研究:动物源肝素多糖不良反应与相关结构关系计量表征技术研究”(2021YFF0600703),2021年-2025年,项目骨干;
国家重点研发计划“医用多糖生物制造关键技术及产业化示范:生物合成多糖构效关系研究与等价性评价”(2021YFC2103100),2021年-2025年,项目骨干;
国家重点研发计划“精准医疗中重大疾病体外诊断试剂及生物药物的计量基标准研究”(2017YFF0205400),2017年-2020年,项目骨干;
国家自然科学基金重大项目培育项目“蛋白糖基化的定量研究及其在新型药物和诊断技术开发中的应用”(91853120),2019年-2021年,第2位;
国家自然科学基金重大项目培育项目“蛋白磷酸化和泛素化在ox-LDL致血管内皮损伤中的动态变化和交互调控网络”(91439111),2015年-2017年,第2位;
国家973计划项目“肿瘤的糖化学生物学前沿研究”(2012CB822100)课题2“糖链探针的生物合成研究”,2012年-2016年,学术骨干;
“重大新药创制”科技重大专项“十二五”规划第二批课题“糖疫苗及相关技术体系的建立与研究”(2012ZX09502-001-005),2012年-2015年,学术骨干。
通讯作者论文
[1] B. Zhang, D. Shi, M. Li, F. Shi*, L. Chi*, A quantitative mass spectrometry method to differentiate bovine and ovine heparins from pharmaceutical porcine heparin, Carbohydrate Polymers, 2023, 301, 120303. (IF = 10.723)
[2] D. Shi, A. Sheng, C. Bu, Z. An, X. Cui, X. Sun, H. Li, F. Zhang, R.J. Linhardt, T. Zhang*, L. Jin*, L. Chi*, A cluster sequencing strategy to determine the consensus affinity domains in heparin for its binding to specific proteins, Analytical Chemistry, 2022, 94, 13987-13994. (IF = 8.008)
[3] Q. Wang, L. Chi*, The alterations and roles of glycosaminoglycans in human diseases, Polymers, 2022, 14, 5014. (IF = 4.967)
[4] D. Shi, C. Bu, P. He, Y. Song, J.S. Dordick, R.J. Linhardt, L. Chi*, F. Zhang*, Structural characteristics of heparin binding to SARS-CoV-2 spike protein RBD of Omicron sub-lineages BA.2.12.1, BA.4 and BA.5, Viruses, 2022, 14, 2696. (IF = 5.818)
[5] D. Shi, P. He, Y. Song, S. Cheng, R.J. Linhardt, J.S. Dordick, L. Chi*, F. Zhang*, Kinetic and structural aspects of glycosaminoglycan-monkeypox virus protein A29 interactions using surface plasmon resonance, Molecules, 2022, 27, 5898. (IF = 4.927)
[6] Q. Chen, F. Li, H. Wang, C. Bu, F. Shi, L. Jin*, Q. Zhang*, L. Chi*, Evaluating the immunogenicity of heparin and heparin derivatives by measuring their binding to platelet factor 4 using biolayer interferometry, Frontiers in Molecular Biosciences, 2022, 9, 966754. (IF = 6.113)
[7] A. Sheng, Q. Chen, M. Yu, R. Xiao, T. Zhang, Z. Wang, R. J. Linhardt, X. Sun*, L. Jin*, L. Chi*, Coupling liquid chromatography and tandem mass spectrometry to electrophoresis for in-depth analysis of glycosaminoglycan drugs: heparin and the multicomponent sulodexide, Analytical Chemistry, 2021, 93, 1433-1442. (IF = 8.008)
[8] B. Zhang, L. Chi*, Chondroitin sulfate/dermatan sulfate-protein interactions and their biological functions in human diseases: implications and analytical tools, Frontiers in Cell and Developmental Biology, 2021, 9, 693563. (IF = 6.081)
[9] D. Shi, A. Sheng, L. Chi*, Glycosaminoglycan-protein interactions and their roles in human disease, Frontiers in Molecular Biosciences, 2021, 8, 639666. (IF = 6.113)
[10] H. Qiu, L. Jin, J. Chen, M. Shi, F. Shi, M. Wang, D. Li, X. Xu, X. Su, X. Yin, W. Li, X. Zhou, R. J. Linhardt, Z. Wang, L.Chi*, Q. Zhang*, Comprehensive glycomic analysis reveals that human serum albumin glycation specifically affects the pharmacokinetics and efficacy of different anticoagulant drugs in diabetes, Diabetes, 2020, 69, 760-770.(IF = 9.337)
[11] L. Ding, S. Xie, S. Zhang, H. Shen, H. Zhong, D. Li, P. Shi*, L. Chi*, Q. Zhang*, Delayed comparison and Apriori algorithm (DCAA): a tool for discovering protein-protein interactions from time-series phosphoproteomic data, Frontiers in Molecular Biosciences, 2020, 7, 606570. (IF = 6.113)
[12] X. Xu, H. Qiu, F. Shi, Z. Wang, X. Wang, L. Jin, L. Chi*, Q. Zhang*, The protein S-nitrosylation of splicing and translational machinery in vascular endothelial cells is susceptible to oxidative stress induced by oxidized low-density lipoprotein, Journal of Proteomics, 2019, 195, 11-22. (IF = 3.855)
[13] Z. Wang, T. Zhang, S. Xie, X. Liu, H. Li, R.J. Linhardt, L. Chi*, Sequencing the oligosaccharide pool in the low molecular weight heparin dalteparin with offline HPLC and ESI-MS/MS, Carbohydrate Polymers, 2018, 183, 81-90. (IF = 10.723)
[14] S. Xie, Y. Guan, P. Zhu, F. Li, M. Yu, R.J. Linhardt, L. Chi*, Lan Jin*, Preparation of low molecular weight heparins from bovine and ovine heparins using nitrous acid degradation, Carbohydrate Polymers, 2018, 197, 83-91. (IF = 10.723)
[15] Z. Wang, L. Chi*, Recent advances in mass spectrometry analysis of low molecular weight heparins, Chinese Chemical Letters, 2018, 29, 11-18. (IF = 8.455)
[16] X. Sun, Z. Guo*, M. Yu, C. Lin, A, Sheng, Z. Wang, R.J. Linhardt, L. Chi*, Hydrophilic interaction chromatography-multiple reaction monitoring mass spectrometry method for basic building block analysis of low molecular weight heparins prepared through nitrous acid depolymerization, Journal of Chromatography A, 2017, 1479, 121-128. (IF = 4.601)
[17] X. Liu, K. St Ange, X. Wang, L. Lin, F. Zhang, L. Chi*, R.J. Linhardt*, Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR, Analytica Chimica Acta, 2017, 961, 91-99. (IF = 6.911)
[18] X. Liu, K. St Ange, L. Lin, F. Zhang, L. Chi*, R.J. Linhardt*, Top-down and bottom-up analysis of commercial enoxaparins, Journal of Chromatography A, 2017, 1480, 32-40. (IF = 4.601)
[19] X. Li, F. Shi*, L. Gong, B. Hang, D. Li, L. Chi*, Species-specific identification of collagen components in Colla Corii Asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach, International Journal of Nanomedicine, 2017, 12, 4443-4454. (IF = 7.033)
[20] J. Yang, L. Chi*, Characterization of structural motifs for interactions between glycosaminoglycans and proteins, Carbohydrate Research, 2017, 452, 54-63. (IF = 2.975)
[21] X. Sun, A. Sheng, X. Liu, F. Shi, L. Jin, S. Xie, F. Zhang, R.J. Linhardt, L. Chi*, Comprehensive identification and quantitation of basic building blocks for low-molecular weight heparin, Analytical Chemistry, 2016, 88, 7738-7744. (IF = 8.008)
[22] Y. Guan, X. Xu, X. Liu, A. Sheng, L. Jin, R.J. Linhardt, L. Chi*, Comparison of low-molecular-weight heparins prepared from bovine lung heparin and porcine intestine heparin, Journal of Pharmaceutical Sciences, 2016, 105, 1843-50. (IF = 3.784)
[23] D. Li, P. Zhang, F. Li, L. Chi, D. Zhu, Q. Zhang*, L. Chi*, Recognition of N-glycoforms in human chorionic gonadotropin by monoclonal antibodies and their interaction motifs, Journal of Biological Chemistry, 2015, 290, 22715-22723. (IF = 5.486)
[24] X. Bai, D. Li, J. Zhu, Y. Guan, Q. Zhang, L. Chi*, From individual proteins to proteomic samples: characterization of O-glycosylation sites in human chorionic gonadotropin and human-plasma proteins. Analytical and Bioanalytical Chemistry, 2015, 407, 1857-1869.(IF = 4.478)
[25] X. Xu, D. Li, L. Chi, X. Du, X. Bai, L. Chi*, Fragment profiling of low molecular weight heparins using reversed phase ion pair liquid chromatography-electrospray mass spectrometry, Carbohydrate Research, 2015, 407, 26-33. (IF = 2.975)
[26] D. Li, L. Chi, L. Jin, X. Xu, X. Du, S. Ji, L. Chi*, Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry, Carbohydrate Polymers, 2014, 99, 339-344. (IF = 10.723)
[27] Z. Wang, D. Li, X. Sun, X. Bai, L. Jin, L. Chi*, Liquid chromatography-diode array detection-mass spectrometry for compositional analysis of low molecular weight heparins, Analytical Biochemistry, 2014, 451, 35-41. (IF = 3.191)
[28] X. Bai, Z. Wang, C. Huang, Z. Wang*, L. Chi*, Investigation of non-enzymatic glycosylation of human serum albumin using ion trap-time of flight mass spectrometry, Molecules, 2012, 17, 8782-94. (IF = 4.927)
[29] Y. Wang, Z. Lu, F. Feng, W. Zhu, H. Guang, J. Liu, W. He, L. Chi*, Z. Li, H. Yu*, Molecular cloning and characterization of novel cathelicidin-derived myeloid antimicrobial peptide from Phasianus colchicus, Developmental and Comparative Immunology, 2011, 35, 314-322. (IF = 3.605)
第一作者论文
[1] L. Chi, J. Wolff, T. Laremore, O. Restaino, J. Xie, C. Schiraldi, T. Toida, J. Amster, R.J. Linhardt*, Structural analysis of bikunin glycosaminoglycan, Journal of the American Chemical Society, 2008, 130, 2617-2625. (IF = 16.383)
[2] L. Chi, E.M. Munoz, H. S. Choi, Y. W. Ha, Y. S. Kim, T. Toida, R.J. Linhardt*, Preparation and structural determination of large oligosaccharides derived from acharan sulfate, Carbohydrate Research, 2006, 341, 864-869. (IF = 2.975)
[3] L. Chi, J. Amster, R.J. Linhardt*, Mass spectrometry for the analysis of highly charged sulfated carbohydrates, Current Analytical Chemistry, 2005, 1, 223-240. (IF = 2.374)
合作论文
[1] Q. Zhang, H. Cao, L. Wei, D. Lu, M. Du, M. Yuan, D. Shi, X. Chen, P. Wang, X. Chen, L. Chi, Y. Zhang, F. Li*, Discovery of exolytic heparinases and their catalytic mechanism and potential application, Nature Communications, 2021, 12, 1263. (IF = 17.694)
[2] J. Ye, H. Xia, N. Sun, C. Liu, A. Sheng, L. Chi, X. Liu, G. Gu, S. Wang, J. Zhao, P. Wang, M. Xiao, F. Wang H. Cao*, Reprogramming the enzymatic assembly line for site-specific fucosylation, Nature Catalysis, 2019, 2, 514-522. (IF = 40.706)
[3] Z. Wang, P.H. Hsieh, Y. Xu, D. Thieker, E.J. Chai, S. Xie, B. Cooley, R.J. Woods, L. Chi, J. Liu*, Synthesis of 3-O-sulfated oligosaccharides to understand the relationship between structures and functions of heparan sulfate, Journal of the American Chemical Society, 2017, 139, 5249-5256. (IF = 16.383)
授权专利
[1] 国际发明专利,Detection method for low molecular weight heparin complete degradation products using hydrophilic interaction chromatography and multiple reaction monitoring tandem mass spectrometry,PCT/CN2017/074966, US10416132B2 (第1位)
[2] 国际发明专利, PIGF-1 assay and kits and components thereof,WO2009155324 A2 (第2位)
[3] 国际发明专利,中国長白山マムシ毒トロンビン様酵素の特徴的なボリベプチド及びその使用,专利号:7120586 (第5位)
[4] 国家发明专利,低分子肝素糖链序列检测方法、系统及测序试剂盒,专利号:202110691317.4 (第1位)
[5] 国家发明专利,一种鉴别猪来源肝素是否掺反刍类动物肝素的方法,专利号:202111527994.9 (第1位)
[6] 国家发明专利,一种低分子肝素基本组成单元的亲水相互作用色谱多反应监测二级质谱联用检测方法,专利号:201610330158.4 (第1位)
[7] 国家发明专利,一种分析蛋白O-糖基化位点的方法,专利号:201410475759.5 (第1位)
[8] 国家发明专利,一种低分子肝素完全降解产物结合柱前衍生的反相色谱质谱联用检测方法,专利号:201310711455.X (第1位)
[9] 国家发明专利,一种低分子肝素部分降解产物的离子对反相色谱质谱联用检测方法,专利号:201310409051.5 (第1位)
[10] 国家发明专利,一种低分子肝素的离子对反相色谱质谱联用检测方法,专利号:201210235395.4 (第1位)
[11] 国家发明专利,一种蛇毒类凝血酶的定量检测方法,专利号:202010753044.7 (第4位)
[12] 国家发明专利,一种白眉蝮蛇蛇毒类凝血酶特征多肽及其应用,专利号:202010752988.2 (第5位)
[13] 国家发明专利,一种白眉蛇毒血凝酶特征多肽及其在注射用蛇毒血凝酶种属鉴别中的应用,专利号:202010754240.6 (第6位)
[14] 国家发明专利,一种马和骡共有特征性多肽及其应用,专利号:201610504874.X (第6位)
软件著作权
[1] 低分子肝素质谱数据解析辅助软件,登记号:2020SR0077987 (第1位)
[2] In silico sequencing软件,登记号:2021SR0390895 (第1位)