临床质谱中心(杨霜 教授)

发布者:金雪明发布时间:2020-10-09浏览次数:2537

临床质谱中心

Center for Clinical Mass Spectrometry



姓  名:Yang Shuang (杨霜)

职称职务:特聘教授

联系电话:0512-6588 0229

电子邮箱:yangs2020@suda.edu.cn

办公地址:苏州市工业园区仁爱路199号苏州大学独墅湖校区二期云轩楼2107

  

个人简历

一、学习工作经历

1、学历背景

1990.9-1994.7哈尔滨工业大学化学系,工学学士

1994.9-1997.2上海交通大学材料科学与工程,工学硕士

2002.1-2003.8新加坡国立大学材料科学系,工学硕士

2003.9-2008.12美国马里兰大学机械工程,哲学博士

2、研究经历

2009.1-2010.12美国马里兰大学微流体中心,博士后

2011.1-2013.9美国约翰霍普金斯医学院,博士后

3、研究和工作经历

2013.10-2016.9美国约翰霍普金斯医学院,青年教师

2016.10-2019.9美国食品药物管理局,副研究员

2019.10-2020.9美国国立卫生研究院牙科和颅面研究所,研究员

2020.10至今:苏州大学药学院,特聘教授 


二、研究方向

1、非小细胞肺癌糖基化机制和早期标志物研究

运用固相化学酶方法、以色谱分析和质谱分析为基础,研究非小细胞肺癌信号传导途径对糖基化的调控机制,探索共价结合药物对肿瘤细胞的抑制和糖基化的调控机理。通过对药物对特异性糖基化的改变,分析在血清中与非小细胞肺癌特异的糖蛋白,筛选出可用于早期诊断的肺癌糖基化蛋白质。

2、蛋白质组学发现基于唾液的肺癌早期生物标志物

唾液是龈沟液、黏膜渗出液和唾液腺腺泡超渗液的混合体,富含疾病生物标志物。唾液腺周围富集毛细血管,对血液渗透性高,使得血液循环中的分子可直接或以外泌体(exosome)的形式分泌到唾液中。其浓度变化可以用作生物标志物以检测早期癌症或监测患者对治疗的反应。通过深度蛋白质组学鉴定唾液中的肺癌生物标志物,并进一步验证其早期诊断以及预后判断患者对治疗反应的能力。早期准确识别高风险人群,以便早期干预治疗和后期追踪观察。

3、血液中神经退行疾病生物标志物的分析和开发

脑脊液(CSF)蛋白质(包括总Tau、磷酸化Tau181和淀粉样蛋白β1-42)的检测和功能成像技术,包括颞中叶的核磁共振成像和氟脱氧葡萄糖正电子发射断层摄影术(PET),已广泛用于诊断神经退行疾病。脑脊液和成像候选生物标记物,如脑脊液可溶性淀粉样前体蛋白(sAPPs)和淀粉样蛋白成像,与已建立的标记物相比也可能具有更好的诊断特性。但是有创性的脑脊液取样并不适合大规模的常规筛查。因此采用血液可大规模对患者筛查和健康监测,通过对血液样本中脑特异性糖蛋白,包括Tau、和淀粉样蛋白β1-42、神经丝蛋白、alpha-突触核蛋白、磷酸化alpha-突触核蛋白和alpha-突触核蛋白寡聚体等蛋白翻译后修饰的研究,探明病变的产生与糖基化、磷酸化和乙酰化的关系,发现与疾病相关的早期症状生物标志物。

4、胰腺癌对尿液中蛋白质组成和糖基化的调控机理

胰腺癌在早期阶段没有特定的症状,绝大多数有症状(>80%)确诊后已属晚期,该阶段的5年生存率只有不到5%,因此基于早期诊断技术的开发显得尤为重要。胰腺癌诊断主要靠不同的成像技术,由于胰腺位于胃和脊柱之间,造成成像技术的局限性检测不到小于2厘米的肿瘤,因此依赖成像结果准确度低。研究表明,腺体的分泌或脱落排泄到尿液,使得尿液含有与胰腺癌相关的蛋白。因此尿液能提供在远隔器官的肾小球滤过后胰腺的信息。使用质谱技术深度分析蛋白质组学,鉴定尿液中与胰腺腺癌相关的生物标志物,并进一步采用免疫组化、酶联免疫吸附测定等方法验证肿瘤标志物。通过对不同阶段病人标志物的筛查,确定其早期诊断标志物,并对病人早期治疗。

5、心脏肥大早期症状标志物的开发

使用质谱的分子分析可以探索心脏肥大中蛋白质翻译后修饰的调控。蛋白质的异常糖基化表明与心脏肥大的发生和发展有关,并导致心力衰竭。鉴定受调节的糖蛋白及其聚糖可以帮助疾病的早期发现和治疗。探明蛋白质糖基化在心肌肥大中的生理和病理作用,发现心肥大生物标志物,为早期治疗提供分子生物学依据。

 6禽流感血凝素和神经氨酸酶糖基化表征

甲型流感病毒每年导致流行性传染,往往要求频繁更新流感疫苗。候选疫苗病毒(CVV)与普通人群中传播的具有血凝素(HA)抗原性的病毒进行匹配而付出了巨大的努力,由于HA神经氨酸酶的突变,使得现有疫苗效力(VE)不高。因此采用分子生物学和质谱蛋白组学分析,通过对HANA抗原和糖基化位点的表征可为更新流感疫苗提供分子信息。

 7新冠刺突糖蛋白和受体的研究

严重急性呼吸综合症冠状病毒2SARS-CoV-2)是新型冠状病毒的一种菌株,已导致2019年大流行的疾病(COVID-19),这种致命病毒已在全球造成超过几千

病例。新冠刺突蛋白是病毒识别并结合宿主受体的第一个接触点,是生物医学研究的重点,以寻求有效的预防和治疗COVID-19。刺突蛋白的大量生产通常在不同的细胞系统中进行。我们初步研究表明细胞表达系统决定刺突蛋白结合域糖基化位点和糖型,不同的表达细胞获得的突刺蛋白受体结合域的位点占有率和连接在糖基化位点的聚糖类型都存在巨大差异。因此影响刺突蛋白和宿主细胞受体之间的相互作用。使用分子生物学、免疫组和蛋白组方法,确定刺突蛋白和受体的糖基化位点和抗原位点,为抑制剂、抗体和疫苗开发提供分子依据。

 8微流体功能芯片的开发和应用

将开发的先进生物分析方法集成到一体化的微流体功能芯片,用于临床样本的检测和疾病诊断。采用聚二甲基硅氧烷(polydimethylsiloxane, PDMS)或聚甲基丙烯酸甲酯(polymethylmethacrylate, PMMA)制作微流体芯片。


三、近五年主要成果

1、论文(按时间倒序)

1S. Yang, Y. Wang, Q. Wang, L. Zhang, M. Matthew, M. Bern, J.F. Cipollo, K.G.T. Hagen, and L.A. Tabak, “Express cells impact glycosite occupancy and types of glycans on SARS-CoV-2 spike glycoprotein,” submitted, 2020.

2S. 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,” revision submitted to Glycoconjugate Journal, 2020.

3S. Yang and J. F. Cipollo, “A versatile solid-phase method for glycan release via enzymatic and chemical reactions,” revision, 2020.

4Q. Wang, T. Wang, S. Yang, C-y. Chung, C-t. Li., J.F. Cipollo, M.J. Betenbaugh, “The interplay of protein engineering and glyco-engineering to generate better-refined antibodies in Chinese hamster ovary cells,” submitted, 2020.

5S. Yang, W.Wu, R-f Shen, J. Sjogren, and J.F. Cipollo, “Optimization of O-GIG for enrichment and release of protein O-glycosylation,” Analytical Chemistry 2020, 92, 10946-10951.

6U.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 2020, revision.

7Qiong Wang, Tiexin Wang, S. Yang, S. Sha, W.W. Wu, Y. Chen, J.T. Paul, R-f. Shen, J.F. Cipollo, and Michael J. Betenbaugh, “Metabolic Engineering Challenges to extending N-glycan pathways in Chinese hamster ovary cells,” Metabolic Engineering, 2020, 61, 301-314.

8N. 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.

9Maira Lorna A. De Leoz 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.

10C. Chung, Q. Wang, S. Yang, S. Chough, J.F. Cipollo, J.P. Balthasa, and M.J. Betenbaugh, “The impact of sialylation linkages of the recombinant butyrylcholinesterases on their pharmacokinetics,” Biotechnology and Bioengineering 2019, 117(1), 157-166.

11H. Wan, J. Gao, H. Yang, S. Yang, R. Harvey et al., “A Neuraminidase Antigenic Drift Contributed to Recent Low Effectiveness of H3N2 Influenza Vaccine,” Nature Microbiology 2019, 4, 2216-2225.

12S. Yang, Z. Yang, P. Wang, “Bioanalysis for precision medicine”, Bioanalysis 2019, 11(11), 1039-1043.

13S. 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).

14S. 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.

15S. Yang*, S. Chatterjee, and J. Cipollo, “The glycoproteomics-mass spectrometry for studying cardiac hypertrophy and heart failure,” Proteomics-Clinical Applications 2018, 12(5), 1870042.

16N. 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,” Prostate Cancer and Prostatic Diseases 2018, 21(1), 137.

17W. Zhou, S. Yang, P.G. Wang, “Matrix effects and matrix effect factors,” Bioanalysis 2017, 9(23), 1839.

18S. Yang* et al., “High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization for glycan extract,” Scientific Reports 2017,7(1), 10216.

19S. 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.

20S. Yang, E. Jankowska, M. Kosikova, H. Xie, and J. Cipollo, “Sialic acid linkage analysis of influenza virus glycoproteins using solid-phase chemical modification,” Analytical Chemistry 2017, 89(17), 9508.

21N. Hoti, S. Yang, P. Aiyetan, B. Kumar, P. Shah, T. Johnson, W.H. Chowdery, H. Zhang, and R. Rodriguez, “Overexpression of Exportin-5 overrides the inhibitory effect of miRNAs regulation control in prostate cancer and stabilizes proteins via post-translational modifications,” Neoplasia 2017, 19(10), 817.

22S. Yang and P. Wang, “Method development of glycoprotein biomarkers for cancers,” Bioanalysis 2017; 9(12):903.

23C. 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.

24S. 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.

25S. Yang*, Y. Hu, L. Sokoll, and H. Zhang, “Quantitative analysis of glycans using a solid-phase method”, Nature Protocols 2017, 12(6), 1229-1244.

26S. Yang*, N. Hoti, W. Yang, Y. Liu, S. Li, and S. Zhang, “Simultaneous analyses of N-linked and O-linked glycans using solid-phase chemoenzymatic method,” Clinical Proteomics 2016; 14 (3):1.

27C. Chung, Q. Wang, S. Yang, B. Yin, H. Zhang, M. Betenbaugh, “Integrated Genome and Protein Editing Swaps α‐2, 6 Sialylation for α‐2, 3 Sialic Acid on Recombinant Antibodies from CHO, ” Biotechnology Journal 2017; 12(2):1600502.

28N. 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.

29D. Do, S. Yang et al., “N-glycan in cockroach allergen regulates human basophil function,” Immunity, Inflammation and Disease 2017; 5(4):386.

30X. Jia, J. Chen, S. Sun, W. Yang, S. Yang, P. Shah, N. Hoti, B. Veltri, and H. Zhang, “Detection of Aggressive Prostate Cancer-Associated Glycoproteins in Urine using Glycoproteomics and Mass Spectrometry,” Proteomics 2016; 16(23):2928.

31S. Sun, P. Shah, S. Toghi Eshghi, W. Yang, N. Trikannad, S. Yang, L. Chen, P. Aiyetan, N. Hoti, Z. Zhang, D.W. Chan, and H. Zhang, “Solid-phase extraction of N-linked glycans and glycosite-containing peptides (NGAG) for comprehensive characterization of glycoproteins,” Nature Biotechnology 2016; 34(1):84.

32S. Yang, M. Wang, L. Chen, B. Yin, G. Song, I.V. Turko, K.W. Phinney, M.J. Betenbaugh, H. Zhang, and S. Li, “QUANTITY: an isobaric tag for quantitative glycomics,” Scientific Reports, 2015; 5:17585.

33P. Shah, X. Wag, W. Yang, S.Toghi Eshghi, S. Sun, N. Hoti, L. Chen, S. Yang, J. Pasay, A. Rubin, and H. Zhang, “Integrated proteomic and glycoproteomic analyses of prostate cancer cells reveals glycoprotein alteration in protein abundance and glycosylation,” Molecular & Cellular Proteomics 2015; 14(10):2753.

34B. Yin, Y. Gao, C. Chung, S. Yang, E. Blake, M.C. Stuczynski, J. Tang, H.F. Kildegaard, M.R. Anderson, H. Zhang, and M.J. Betenbaugh, “Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N-glycan branching and sialylation,” Biotechnology and Bioengineering 2015; 112 (11):2343.

35S. Yang*, A. Rubin, S. Toghi Eshghi, and H. Zhang, “N-linked glycoproteins: isolation, identification, and quantitation,” Proteomics 2015; 16:241.

36S. Yang, S. Mishra, L. Chen, J. Zhou, D.W. Chan, S. Chatterjee, and H. Zhang, “An integrated glycoprotein immobilization method for glycopeptide and glycan analysis of cardiac hypertrophy,” Analytical Chemistry 2015; 87(19):9671.

37P. Shah, B. Zhang, C. Choi, S. Yang, J. Zhou, R. Harlan, Y. Tian, Z. Zhang, D.W. Chan, and H. Zhang, “Tissue proteomics using chemical immobilization and mass spectrometry,” Analytical Biochemistry 2015; 469:27. 

2、专利

1)发明专利, Quaternary amine containing isobaric tag for quantitative glycan profiling. 专利号:20160252518 A1 (US 10,254,291 B2)

1)发明专利,Isobaric aldehyde-reactive tags for and analysis of glycans using same. 专利号:World patent #2,014,040,072 A1; US 2015/0241437 A1 (US 99,394,44 B2).

1)发明专利,Glycan and glycopeptide capture and release using reversible hydrazone-based method. 专利号:World patent # 2,012,170,491; US 2014/0135235 A1. 

3、目前承担项目

国家自然科学基金项目批准号:81871955β-1,4 半乳糖基转移酶3 表达升高引起的异常糖基化修饰对胃癌发展的作用机制研究,2019

四、主要荣誉

1. 2008HPLC国际会议获得最佳墙报(Best Poster

2. 2011年国际糖生物协会年会Travel Award

3. 2012年度美国约翰霍普金斯医学院青年研究者奖(Young Investigator Award

4. 2012年第11届世界蛋白组会议Travel Award

5. 2012年第11届世界蛋白组会议最佳报告奖

6. 2013年国际糖聚合物会议Travel Award

7. 2017年美国化学协会北美色谱青年研究者奖(Young Investigator Award

8. 2018年美国食品药物管理局科学成就奖(Scientific Achievement Award

五、社会兼职

担任Analytical Chemistry, Analytica Chimica Acta, ChemComm, Chemical Science, Clinical Proteomics, Electrophoresis, Genomics Proteomics & Bioinformatics, Journal of Proteome Research, Journal of Hematology & Oncology, The Journal of Pathology, Journal of Chromatography A, Journal of Separation Science, Molecular BioSystems, Rapid Communication in Mass Spectrometry, The Electrochemical Society Journal等国际学术期刊特邀审稿人。