杨霜

发布者:金雪明发布时间:2020-10-16浏览次数:5940

本团队长期招聘教授、副教授、研究员、师资和统招博士后。



杨     霜


特聘教授 | 苏州大学药学院

仁爱路199号苏州大学独墅湖校区二期云轩楼2107

邮箱:yangs2020@suda.edu.cn



个人概述

研究领域涵盖化学和生物工程,侧重细胞表面糖基化和人体体液疾病糖蛋白标志物的发现和临床应用。围绕糖生物并利用先进质谱技术,开发蛋白糖基化富集和分离技术,研究异常糖基化与肿瘤调控机理,退性神经特异糖基化,利用糖基化调控机制和新技术发现糖蛋白早诊和预后标志物。

 

University of Maryland at College Park攻读博士期间,研究微流体芯片用于蛋白和多肽分离,该技术应用于On Chip聚糖和糖肽分析。随后在University of Maryland at College Park从事博士后工作期间,开发用高表面积纳米纤维(Nanofilament)用于激光解离聚糖和大分子质谱检测。在Johns Hopkins University博士后和任教期间,开发了基于固相化学酶的聚糖和糖蛋白分析方法,发明基于二级质谱的同位素聚糖定量标签(iARTsQUANTITY),探索前列腺癌和心血管疾病异常糖基化。2016年加入美国食品和药品管理局(FDA)后,开发唾液酸链接修饰方法,并首次解决了O-糖基化的富集和分离难题,成功应用于肺癌、禽流感和新冠糖基化和疫苗表征。在NIH期间开始研究肿瘤粘蛋白(MUCO-糖基化与疾病产生和进程。

 

参与美国国立卫生研究院子课题 (NIH) 6项、主持美国国立卫生研究院中小企业创新研究 (SBIR) 1项、共同主持美国马里兰州创新项目 (MII) 1项。自2016年开始担任华人北美质谱协会 (CASMS) 委员,组织2017ACS年会分析化学会议主持。发表学术论文70余篇,包括Nat ProtocNat Rev ChemNat MicrobiolNat BiotechnolMetab Eng, Anal ChemLab Chip等期刊。

 

研究课题

            基于唾液肺癌岩藻糖标志物发现和应用,肺癌岩藻糖糖基化调控机制

            肺泡灌洗液和胸腔积水与肺部疾病糖基化

            基于尿样和消化道体液外泌体胰腺癌异常糖基化和标志物的研究

            胰腺炎症和癌诊糖基化对丝氨酸蛋白酶活性的调控

            帕金森和老年痴呆体液早期症状标志物筛查

            大分子糖蛋白的表征和与药物作用

 

教育背景

            University of Maryland at College Park, Mechanical Engineering, Ph.D., 2008

            National University of Singapore, Materials Science, M.S., 2003

            上海交通大学,材料科学与工程,硕士,1997

            哈尔滨工业大学,化学,本科,1994

 

工作和研究经历

上海哈威新材料技术有限公司,上海,中国

质量控制经理(1997.3-1999.12)

职责和技能:

编写通信光电缆保护HDPE管道的质量控制标准和实施日常生产质量检验;


起草公司ISO9000质量标准并于1999年获批。



三星公司上海技术和市场部,上海,中国

技术支持工程师   (2000.1-2001.12)

职责和技能:

与客户讨论并将各种电子原材料使用过程中遇到的技术改进总结及时向总部反馈,产品包括银浆料、手机电池电解液、电子封装用塑料材料;


根据客户生产过程中遇到的潜在质量和可靠性问题提出修改意见。



University   of Maryland at College Park, Maryland, USA

博士后/初创公司科学家   (2009.1-2010.12)

负责项目:

采用基于塑料和硅芯片设计用于大分子一维及二维分离的生物功能微流体芯片,可分析蛋白质和其他生物大分子;


在硅芯片上刻蚀纳米纤维产生高表面积基材用于激光解离聚糖和大分子质谱检测 (LDI-MS)


使用COC塑料开发集成等电聚焦(IEF)和高效液相色谱(HPLC)分离微流体芯片,富集分离蛋白质。



Johns   Hopkins University, Pathology, Maryland, USA

博士后   (2011.1-2013.9)

项目和成果:

设计基于固相化学酶技术,在固相上衍生唾液酸并富集N-聚糖;


独创一种从复杂样本中采用微酸条件共价结合、酸性条件水解的可逆表面反应功能团,用于分析带有还原端的聚糖;


优化用于分析蛋白糖基化位点、占有率、位点糖组成及丰度、整体蛋白含量的方法;


首创同位素聚糖标记物标签,使用二级质谱定量聚糖相对含量。



Johns   Hopkins University, Pathology, Baltimore, Maryland, USA

助理教授   (2013.10-2016.9)

项目和成果:

成功使用福尔马林定型临床病理切片质谱成像,实现切片组织大分子和聚糖在肿瘤病人中的分子成像(MALDI-MSI


研究心血管疾病(心肥大)蛋白糖基化的变化,发现心肥大中唾液酸糖基化高表达;


成功开发使用移液枪管尖制备的高通量样本制备产品(AutoTip),可在自动化液体操作同时处理96-384种临床样本。使用该技术分析了前列腺癌患者尿样种聚糖著称,发现支链、岩藻糖和唾液酸表达增加;


创建了高通量用于依次分析N-聚糖和O-聚糖的固相化学酶系统,成功分析卵巢癌细胞聚糖结构和丰度;


发明了季胺同位素聚糖标签,用于二级质谱聚糖的相对定量,可用于LC-MS/MS结构和定量分析。



Food and   Drug Administration, CBER, Silver Spring, Maryland, USA

副研究员(2016.10-2019.9)

项目和成果:

独创了用于分析复杂蛋白O-糖基化的固相化学酶方法,采用新发现的O-蛋白酶(OpeRATOR),在固相上衍生聚糖和氨基酸,从带有O-聚糖的丝氨酸和谷氨酸N端酶切富集得到;


实现带有唾液酸糖蛋白固相上化学衍生,成功将2,32,6链接唾液酸分两步修饰,并使用蛋白酶水解和亲水作用富集(HILIC)研究唾液酸糖蛋白在疾病中的特性和功能;


参与药物和生物制剂的评审工作,包括 pre-IND, IND, 和化学、生产、质量控制等工艺的审查(CMC);


评审流感疫苗和其他疫苗的CMC流程,包括Pneumococcal   oligosaccharide conjugated vaccines, Streptococcus pneumoniae oligosaccharide   conjugated vaccines.



National   Institutes of Health, NIDCR, Bethesda, Maryland, USA

研究员(2019.10-2020.9)

项目和成果:

建立了质谱检验中心(Biological Chemistry Section),包括MALDI-MS (Bruker), LC-MS   (Thermo)和样本处理工作平台;


建立用于质谱分子的各种样本制作流程(SOP),确立了质谱中离子碎片化用于O-糖肽的分析方法,即ETDEThcD


研究了新冠突刺蛋白的糖基化修饰,发现在不同细胞表达对突刺蛋白糖基化的决定作用。

 

获奖、专利和学术论文

获奖

            2008年美国巴尔的摩国际HPLC年度会议药物分析创新最佳墙报

            2011年美国西雅图国际糖生物协会年度会议旅游奖

            2012年美国约翰霍普金斯医学院年度青年科学家奖

            2012年波士顿第11届国际HUPO会议旅行奖

            2012年波士顿第11届国际HUPO会议会议报告奖第3

            2013年美国国家卫生研究员/食品和药品管理局年度会议最佳墙报

            2013年第22届中国大连国际糖缀合物会议旅行奖

            2017年北美华人色谱青年科学家奖(ACS-CACA

            2018年美国食品和药品管理局(FDA)科技成就奖

            2021年江苏生双创博士

 

授权和申请专利

12/20/2021        S. Yang, A. Yang, Z. Yang, 一种岩藻糖糖蛋白荧光显色载体的制备方法、荧光强度参考载体的制作方法及用途。苏州大学。Application No. 202111562311.3.

12/8/2021          S. Yang, J. Li, 一种基于固相富集结合O-糖肽酶切分析Tn抗原的方法。苏州大学。Application No. 202111487621.3.

11/25/2021        S. Yang, S. Yue, 一种基于固相糖蛋白富集和Tn糖肽酶切的分析方法和应用。苏州大学。Application No. 202111411385.7.

11/22/2021        S. Yang, W.H. Hu, 固相富集O-GlcNAc糖肽的制备方法。苏州大学。Application No. 202111388738.6.

10/28/2021        S. Yang, J.H. Jiang, Z.Y. Gao, 一种基于唾液酸特异性岩藻糖基化结构糖谱及其检测方法和应用。苏州大学。Application No. 202111259337.0.

04/29/2021        S. Yang, S. Li, 酸水解化合物的合成方法及其用于固相耦合糖蛋白、固相改性衍生和富集糖肽的方法。Application No. 202110466156.9.

03/17/2021        S. Yang, Z. Liu, 糖肽富集材料及其制备方法和富集方法。苏州大学。Application No. 20210284482.8.

02/05/2021        S. Yang, S. Li, 固相标记物及其制备方法、固相载体多通道多肽和糖肽及其制备方法。苏州大学。Application No. 202110163100.6.

11/05/2021        S. Yang, A. Yang, 一种基于真空泵吸的生物流体与组织分离的装置。苏州大学。专利号:202120042939.X.

12/16/2020        S. Yang, S. Li, 一种基于固相法分离N-糖肽和O-糖肽的方法。苏州大学。Application No. 202011481041.9.

07/27/2018        S. Li, M. Wang, S. Yang, 用于多糖分析的一种同位素标签试剂的制备和应用。Nanjing Apollomics. Application No. 20180843616.3.

06/13/2017        S. Yang, H. Zhang, AutoTip for high-throughput analysis of N-glycans, Johns Hopkins University, pending.

10/12/2015        S. Li, S. Yang, and H. Zhang, Quaternary amine containing isobaric tag for quantitative glycan profiling. University of Maryland and Johns Hopkins University. US patent 20160252518 A1 (US 10,254,291 B2)

05/13/2014        H. Zhang, S. Yang, P. Shah, S. Sun, Solid phase glycan and glycopeptide analysis and microfluidic chip for glycomic extraction, analysis and methods for using same. Johns Hopkins University. World patent #2,014,040,066 A1; US 2015/0233903 A1.

03/13/2014        H. Zhang, S. Yang, Shuwei Li, Isobaric aldehyde-reactive tags for and analysis of glycans using same. Johns Hopkins University. World patent #2,014,040,072 A1; US 2015/0241437 A1 (US 99,394,44 B2).

12/13/2012        H. Zhang, S. Yang. Glycan and glycopeptide capture and release using reversible hydrazone-based method. Johns Hopkins University. Patent #WO2012170491A1; US20140135235A1.

 

2017年以来发表的论文

1.     Z. Gao, M. Xu, S. Yue, H. Shan, J. Xia, J. Jiang, and S. Yang*, Aberrant sialylation and fucosylation of body fluid glycoproteins in lung cancer,” ACS Omega (revision), 2022.

2.     M. Xu, H. Jin, Y. Han, Z. Wu, J. Chen, C. Mao, X. Zhang, P. Hao, C. Liu, S. Yang*, “Mass spectrometry-based analysis of serum N-glycosylation changes in patients with Parkinson’s disease,” ACS Chemical Neuroscience (revision), 2022.

3.     Q. Wang, T. Wang, R. Zhang, S. Yang, K. McFarland, C-y. Chung, H. Jia, L. Wang, J.F. Cipollo, M.J. Betenbaugh*, “The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions,” Biotechnology and Bioengineering 2021, 10.1002/bit.27953. (IF: 4.260). (Q2)

4.     Q. Wang, Y. Wang, S. Yang, C. Lin, L. Aliyu, Y. Chen, L. Parsons, Y. Tian, H. Jia, A. Pekosz, M.J. Betenbaugh, J.F. Cipollo, “A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates,” Frontiers in Chemistry 2021, 9:735558,1-16. (Q2)

5.     Y. Wang, Q. Wang, Z. Wu, W. Hu, P. Hao, and S. Yang*, “Impact of expressing cells on glycosite occupancy and glycan of SARS-CoV-2 spike glycoprotein,” ACS Omega 2021, 6(24), 15988-15999. (IF: 3.512) (Q3)

6.     U.H. Mortensen*, D.C. Anyaogu, A.H. Hansen, J.B. Hoof, N.I. Majewska, J.T. Paul, K.R. Nielsen, T.J. Hobley, S. Yang, H. Zhang, and M. Betenbaugh, “Glycoengineering of aspergillus nidulans to produce precursors for humanized N-glycan structures,” Metabolic Engineering 2021, 67, 153-163. (IF: 7.263) (Q1)

7.     M. Xu, W. Hu, Z. Liu, J. Xia, S. Chen, P.G. Wang, S. Yang*, “Glycoproteomic bioanalysis of exosomes by LC-MS to early diagnose pancreatic cancer,” Bioanalysis 2021, 13(11), 861-864. (IF: 2.371) (Q4)

8.     S. Yang*, J. Xia, Z. Yang, M. Xu, S. Li, “Lung cancer molecular mutations and abnormal glycosylation as biomarkers for early diagnosis”, Cancer Treatment and Research Communications 2021, 21(7), 100311, 1-11 (IF: 0.580)

9.     M. Xu, M. Zhou, S. Li, X. Zhen, and S. Yang*, “Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: a glycoproteomic approach,” Journal of Neuroscience Research 2021, 99(5), 1308-1324. (IF: 3.921) (Q2)

10.  H. Yu, J. Wang, Z. Tang, X. Li, M. Yin, F. Zhang, J. Shu, W. Chen, S. Yang*, and Z. Li*, “Integrated glycomics strategy for evaluation of glycosylation alterations in salivary proteins associated with type 2 diabetes mellitus,” RSC Advances 2020, 10, 39739-39752. (IF: 3.267) (Q3)

11.  S. Yang, Y. Wang, M. Mann, Q. Wang, E. Tian, L. Zhang, J.F. Cipollo, K.G.T. Hagen, and L.A. Tabak*, “Improved online LC-MS/MS identification of O-glycosites by EThcD fragmentation, chemoenzymatic reaction, and SPE enrichment,” Glycoconjugate Journal 2020, DOI: 10.1007/s10719-020-09952-w. (IF: 3.010) (Q3)

12.  S. Yang*, W. Wu, R-f Shen, L. Parsons, and J.F. Cipollo*, “Optimization of O-GIG for O-Glycopeptide Characterization with Sialic Acid Linkage Determination,” Analytical Chemistry 2020, 92, 10946-10951. (IF: 6.785) (Q2)

13.  Q. Wang, T. Wang, S. Yang, S. Sha, W.W. Wu, Y. Chen, J.T. Paul, R-f. Shen, J.F. Cipollo, and M.J. Betenbaugh*, “Metabolic Engineering Challenges to extending N-glycan pathways in Chinese hamster ovary cells,” Metabolic Engineering, 2020, 61, 301-314. (IF: 7.263) (Q1)

14.  N. de Haan*, S. Yang, J.F. Cipollo, and M. Wuhrer, “Glycomics studies using sialic acid derivatization and mass spectrometry,” Nature Reviews Chemistry 2020, 4, 229-242. (IF: 33.566) (Q1)

15.  M. Lorna A. De Leoz,…, S. Yang et al., “NIST interlaboratory study on glycosylation analysis of monoclonal antibodies: comparison of results from diverse analytical methods,” Molecular & Cellular Proteomics 2020, 19(1), 11-30.  (IF: 4.870) (Q2)

16.  C. Chung, Q. Wang, S. Yang, S. Chough, J.F. Cipollo, J.P. Balthasa, and M.J. Betenbaugh*, “The impact of sialylation linkage-type on the pharmacokinetics of recombinant butyrylcholinesterases,” Biotechnology and Bioengineering 2019, 117(1), 157-166. (IF: 4.260) (Q2)

17.  H. Wan*, J. Gao, H. Yang, S. Yang, R. Harvey et al., “The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain,” Nature Microbiology 2019, 4, 2216-2225. (IF: 14.300) (Q1)

18.  S. Yang, Z. Yang, P. Wang*, “Bioanalysis for precision medicine”, Bioanalysis 2019, 11(11), 1039-1043. (IF: 2.371) (Q4)

19.  S. Yang*, P. Onigman, W. Wu, J. Sjogren, H. Nyhlen, R-F. Shen, and J. Cipollo*, “Deciphering protein O-glycosylation: solid-phase chemoenzymatic cleavage and enrichment,” Analytical Chemistry 2018, 90(13), 8261-8269 (ACS Editor’s Choice). (IF: 6.785) (Q2)

20.  S. Yang*, W. Wu, R-F. Shen, M. Bern, and J. Cipollo*, “Identification of sialic acid linkages on intact glycopeptides via differential chemical modification using intactGIG-HILIC,” Journal of the American Society for Mass Spectrometry 2018, 29(6), 1273-1283. (IF: 3.150) (Q3)

21.  S. Yang*, S. Chatterjee*, and J. Cipollo, “The glycoproteomics-mass spectrometry for studying cardiac hypertrophy and heart failure,” Proteomics-Clinical Applications 2018, 12(5), 1870042, 1-13. (IF: 2.568) (Q3)

22.  N. Hoti, S. Yang, Y. Hu, P. Shah, M. Haffner, and H. Zhang*, “Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells,” Prostate Cancer and Prostatic Diseases 2018, 21(1), 137, 1-10. (IF: 4.311) (Q2)

23.  W. Zhou, S. Yang, P.G. Wang*, “Matrix effects and matrix effect factors,” Bioanalysis 2017, 9(23), 1839-1844. (IF: 2.371) (Q4)

24.  S. Yang*, D. Clark, Y. Liu, S. Li, H. Zhang, “High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization for glycan extract,” Scientific Reports 2017,7(1), 10216, 1-11. (IF: 3.998) (Q3)

25.  S. Yang*, L. Chen, D.W. Chen, Q. Li, and H. Zhang, “Protein signatures of molecular pathways in non-small cell lung carcinoma (NSCLC): comparison of glycoproteomics and global proteomics,” Clinical Proteomics 2017,14(1), 31, 1-15. (IF: 2.568) (Q3)

26.  S. Yang, E. Jankowska, M. Kosikova, H. Xie, and J. Cipollo*, “Solid-Phase Chemical Modification for Sialic Acid Linkage Analysis: Application to Glycoproteins of Host Cells Used in Influenza Virus Propagation,” Analytical Chemistry 2017, 89(17), 9508-9517. (IF: 6.785) (Q2)

27.  N. Hoti*, S. Yang, P. Aiyetan, B. Kumar, Y. Hu, D. Clark, A.U. Eroglu, P. Shah, T. Johnson, W.H. Chowdery, H. Zhang, and R. Rodriguez, “Overexpression of Exportin-5 Overrides the Inhibitory Effect of miRNAs Regulation Control and Stabilize Proteins via Posttranslation Modifications in Prostate Cancer,” Neoplasia 2017, 19(10), 817-829. (IF: 5.696) (Q2)

28.  S. Yang* and P. Wang, “Method development of glycoprotein biomarkers for cancers,” Bioanalysis 2017; 9(12):903-906. (IF: 2.371) (Q4)

29.  C. Chung, Q. Wang, S. Yang, S.A. Ponce, B.J. Kirsch, H. Hang, M.J. Betenbaugh*, “Combinatorial genome and protein engineering yields monoclonal antibodies with hypergalactosylation from CHO cells,” Biotechnology and Bioengineering 2017, 114(12), 2848-2856. (IF: 4.002) (Q2)

30.  S. Yang*, L. Zhang, S. Thomas, Y. Hu, S. Li, J. Cipollo, and H. Zhang, “Modification of sialic acids on solid-phase: accurate characterization of protein sialylation,” Analytical Chemistry 2017, 89(12), 6330-6335. (IF: 6.785) (Q2)

31.  S. Yang*, Y. Hu, L. Sokoll, and H. Zhang*, “Simultaneous quantification of N- and O-glycans using a solid-phase method”, Nature Protocols 2017, 12(6), 1229-1244. (IF: 10.419) (Q1)

32.  S. Yang*, N. Hoti, W. Yang, Y. Liu, S. Li, and H. Zhang*, “Simultaneous analyses of N-linked and O-linked glycans using solid-phase chemoenzymatic method,” Clinical Proteomics 2016, 14(3), 1-11. (IF: 2.568) (Q3)

33.  C. Chung, Q. Wang, S. Yang, B. Yin, H. Zhang, M. Betenbaugh*, “Integrated Genome and Protein Editing Swaps α2, 6 Sialylation for α2, 3 Sialic Acid on Recombinant Antibodies from CHO,” Biotechnology Journal 2017, 12(2), 1600502, 1-11. (IF: 3.910) (Q2)

34.  N. Hoti*, P. Shah, Y. Hu, S. Yang, and H. Zhang, “Proteomics analyses of prostate cancer cells reveals cellular pathways associated with androgen resistance,” Proteomics 2017, 17, 6, 1-10. (IF: 3.254) (Q3)

35.  D. Do, S. Yang, X. Yao, R.G. Hamilton, J.T. Schroeder, P. Gao*, “N-glycan in cockroach allergen regulates human basophil function,” Immunity, Inflammation and Disease 2017, 5(4), 386-399. (IF: 2.625) (Q4)

 

主持和参与的项目

1.     CNSF 81871955: Mechanism of abnormal glycosylation modification on gastric cancer development (2019-2022) (PI).

2.     P01HL107153 (NIH/NHLBI): Glycoconjugates and cardiovascular disease (2011-2018) (Co-Investigator).

3.     HHSN268201000032C (N01-HV-00240) (NIH/NHLBI): Johns Hopkins proteomic innovation center in heart failure (2010-2015) (Co-Investigator).

4.     U24CA115102 (NIH/NCI): Clinical and analytical validation of cancer biomarkers (2010-2015) (Co-Investigator).

5.     U01CA152813 (NIH/NCI): Glycoprotein biomarkers for the early detection of aggressive prostate cancer (2012-2015) (Co-Investigator).

6.     Maryland Innovation Initiative (MII): QUANTITY: A novel analysis kit for robust drug development, clinical (2015-2016) (Co-PI).

7.     1R21CA191715-01 (NIH/NCI): AGX1/2 Inhibitors as key modulators of the hexosamine biosynthetic (2014-2017) (Co-Investigator).

8.     CBET 1512265 (NSF/ENG/CBET): Integrating novel nutrient feeding strategies with computational (2015-2018) (Co-Investigator).

9.     1R43GM084525-01 (NIH/SBIR): Nanofilament silicon for ultrasensitive proteomics (2008-2010) (PI).