| 研究成果： |
主要研究方向为糖生物学在癌症和炎症研究中的应用和多核核磁共振在化学生物学中的应用。
代表性成果可总结为以下几个方面： （1) 聚糖结构在癌细胞中的变异及功能的研究。与法国里尔第一大学Catherine Robbe-Masselot教授合作，致力于癌细胞蛋白糖基化的特征并寻找潜在的癌细胞生物标志物的研究。利用MALDI-TOT质谱方法研究癌细胞中糖蛋白糖链结构。阐明了聚糖结构在癌细胞中的变化以及对癌细胞的生长凋亡平衡的影响。这项基础研究对解读癌细胞的产生和转移具有重要的意义，对重新激发癌细胞程序化死亡提供了理论依据。
（2）糖基转移酶的活性和抑制剂的研发。与南开大学生命科学院王磊教授合作，从事致命大肠杆菌O157的O－抗体糖基转移酶的研究，通过质谱与核磁共振的手段解析酶产物的结构, 为选择针对性抗菌药的研究奠定了基础。与加拿大女王大学化学系Walter A. Szarek教授长期合作, 研发了一系列糖基转移酶抑制素，其中具有特异性的抑制剂能有效抑制糖基转移酶在癌细胞中的生物活性，从而改变癌细胞表面聚糖的结构，例如降低铜绿假单胞菌对肺表面细胞的粘附性。为了更深入的了解抑制剂的作用机理，设计并合成了大量与抑制剂结构相似的化合物，研究化合物的构效关系。这项研究对新一代消炎药和抗癌药的研发具有重要意义。
（3）多核核磁共振技术研究化学生物学反应物质的本构关系。即用核磁共振技术研究药类化合物装载的宾主系统、药物的化学作用机理以及生物气体信号分子NO和H2S之间的相互作用机理。运用多核核磁共振技术结合紫外、红外光谱以及理论计算解决了一系列困扰化学生物学领域的难题。在同位素标记化合物的合成、核磁共振波谱分析方面积累了丰富的经验。在过去的几年中，已成功解决了化学界对硝酰基化合物化学性质及活性结构的争议；解决了困扰化学界一百七十年之久的格梅林反应Gmelin reaction化学品色现象的争议，该论文被选为期刊代表性文章, 并被美国化学会《C&EN News》报道；构建直接检测降压药硝普钠sodium nitroprusside和2-巯基丁二酸 mercaptosuccinic acid反应的不稳定“红色产物”的方法，对此类降压药物的生物作用机理提供了更深入的认识，论文被期刊主编评选为热点文章。 （4）透明质酸衍生物在关节炎大鼠及创伤大鼠模型中的治疗效果研究，揭示透明质酸衍生物具备组织修复、促进愈合、关节润滑和抗炎等“一石多鸟”的作用机制。
代表作： 1. Role of Glycans onKey Cell Surface Receptors That Regulate Cell Proliferation and Cell Death. Yin Gao, Xue Luan, Jacob Melamed, Inka Brockhausen*, Cells, 2021, 10, 1252. https://doi.org/10.3390/cells10051252.
2. 17O NMR spectroscopy-assisted in vitro bioactivity studies of the intermediates formed via Na2S and RSNO cross-linking reactions. Xingyu Zhu and Yin Gao*, RSC Advances,2020,10,39617-39626.
3. The expression and functional analysis of the sialyl-T antigen in prostate cancer. Ruifeng Bai, Xue Luan, Yu Zhang, Catherine Robbe-Masselot, Inka Brockhausen, Yin Gao*, Glycoconj J, 2020,37(4):423-433.
4. N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models.
Lanzhou Li#, Di Wang#, Ruifeng Bai, Xueju Wang, Chunyu Wang, Yin Gao*, Tassos Anastassiades*, Pharmaceutical Biology, 2019; 57(1), 717-728, https://doi.org/10.1080/13880209.2019.1672755.
5. A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen.
Yin Gao#, Yao Sun#, Hao Yang, Pengyu Qiu, Zhongcheng Cong, Yifang Zou, Liu Song, Jianfeng Guo* and Tassos P. Anastassiades, International Journal of Molecular Sciences, 2019;20(15). pii: E3722. doi: 10.3390/ijms20153722.
6. Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation
Na Qu, Yating Sun, Yujing Li, Fei Hao, Pengyu Qiu, Lesheng Teng, Jing Xie*; Yin Gao*, Biomed Eng Online. 2019;18(1):11. doi: 10.1186/s12938-019-0624-7.
7. Recent advances in single-cell analysis by mass spectrometry.
Lei Yin, Zhi Zhang, Yingze Liu, Yin Gao* and Jingkai Gu*, Analyst. 2019;144(3):824-845. doi: 10.1039/c8an01190g.
8. Antitumor effect of a liposome-encapsulated β1,4-galactosyltransferase inhibitor. Guangsheng Cai, Kun Wang, Na Qu, Pengyou Qiu, Jason Z. Vlahakis, Walter A. Szarek, Robert J. Lee*, Yin Gao*, International Journal of Pharmaceutics, 2018, 552: 388-393.
9. Solid-State 15N and 17O NMR of S-Nitrosothiols.
Yin Gao, Yizhe Dai, Gang Wu, Journal of Physical Chemistry B, 2017, 121: 7311-7317.
10. Direct NMR detection of the unstable “red product” from reaction between nitroprusside and 2-mercaptosuccinic acid.
Yin Gao, Brendan Mossing, Gang Wu, Dalton Transactions, 2015, 44(47): 20338-20343.
11. Solving the 170-Year-Old mystery about red-violet and blue transient intermediates in the Gmelin reaction.
Yin Gao, Abouzar Toubaei, Xianqi Kong, Gang Wu, European Journal of Chemistry, 2015-November, 21: 17172-17177.
12. Acidity and hydrogen exchange dynamics of iron(II)-bound nitroxyl in aqueous solution.
Yin Gao, Abouzar Toubaei, Xianqi Kong, Gang Wu, Angewandte Chemie International Edition, 2014, 53(43): 11547-11551.
13. Acceptor specificities and selective inhibition of recombinant human Gal- and GlcNAc-transferases that synthesize core structures 1, 2, 3 and 4 of O-glycans.
Yin Gao, Rajindra P. Aryal, Tongzhong Ju, Richard D. Cummings, Gagandeep Gahlay, Donald L. Jarvis, Khushi Matta, Jason Z. Vlahakis, Walter A. Szarek, Inka Brockhausen*, Biochimica et Biophysica Acta, 2013, 1830(8): 4274-4281.
14. Selective inhibition of glycosyltransferases by bivalent imidazolium salts.
Yin Gao, Jason Z. Vlahakis, Walter Szarek, Inak Brockhausen, Bioorganic & Medicinal Chemistry, 2013-March, 21(5): 1305-1311 (Impact factor: 3.21).
15. Biochemical characterization of WbdN, a β1,3-glucosyltransferase involved in O-antigen synthesis in enterohemorrhagic Escherichia coli O157.
Yin Gao#, Bin Liu#, Scott Strum, John S. Schutzbach, Tatyana N. Druzhinina, Natalia S. Utkina, Vladimir I. Torgov, Leonid L. Danilov, Vladimir V. Veselovsky, Jason Z. Vlahakis, Walter A. Szarek, Lei Wang, Inka Brockhausen, Glycobiology, 2012, 22(8): 1092 -1102.
16. Functional identification of bacterial glucosyltransferase WbdN, Methods.
Yin Gao, Anna Vinnikova, Inka Brockhausen, Mol. Biol., 2013, 1022: 199 – 214.
15. Glycosylation potential of human prostate cancer cell lines.
Yin Gao, Vishwanath Chachadi, Pi-Wan Cheng, Inka Brockhausen, Glycoconjugate Journal, 2012, 29(7): 525-537.
17. Specificity of β1,4-galactosyltransferase inhibition by 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-D-glucopyranoside.
Yin Gao, Carmen Lazar, Walter A. Szarek, Inka Brockhausen, Glycoconjugate Journal, 2010, 27(7): 673 -684.
18. Analysis of therapeutic monoclonal antibody glycoforms by mass spectrometry for pharmacokinetics study.
Yuting Cong, Lianghai Hu, Zhang Zhang, Yin Gao, Mingming Dong, Hongqiang Qin, Mingliang Ye, Jingkai Gu, Hanfa Zou, , Talanta, 2017, 165: 664-670.
19. Enhanced delivery of paclitaxel using electrostatically-conjugated hercepin-bearing PEI/PLGA nanoparticles against HER-positive brest cancer cells.
Kongtong Yu, Jinglong Zhao, Zunkai Zhang, Yin Gao, Yulin Zhou, Lesheng Teng, Youxin Li, International Journal of Pharmaceutics, 2016, 497: 78-87.
20. Determination of thymopentin in beagle dog blood by liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study. Meiyun Shi, Yan Yang, Xiaotong Zhou, Lanlan Cai, Chunxue Fang, Can Wang, Heping Sun, Yantong Sun, Yin Gao, Jingkai Gu, J. Paul Fawcett, Journal of Separation Science, 2015, 38(8): 1351–1357.
21. Characterization of two UDP-Gal: GalNAc-Diphosphate-lipid β1,3Galactosyltransferases Wbwc from Escherichia coli serotypes O104 and O5.
Shuo Wang, Diana Czuchry, Bin Liu, Anna N. Vinnikova, Yin Gao, Jason Z. Vlahakis, Walter A. Szarek, Lei Wang, Feng Lu, Inka Brockhausen, Journal of Bacteriology, 2014, 196 (17): 3122 – 3133.
22. Determination of a deuterohemin–peptide conjugate in rat plasma by liquid chromatography–tandem mass spectrometry and application to a preclinical pharmacokinetic study.
Hao Wang, Yantong Sun, Wei Guo, Chunxue Fang, J. Paul Fawcett, Wei Lia, Yin Gao, Yan Yang, Jingkai Gu, Journal of Pharmaceutical and Biomedical Analysis, 2014, 98: 401-406.
23. Enzyme-substrate complexes of allosteric citrate synthase: evidence for a novel intermediate in substrate binding.
Harry W. Duckworth, Nham T. Nguyen, Yin Gao, Lynda J. Donald, Robert Maurus, Ayead Ayed, Brigitte Bruneau, Gary D. Brayer, Biochimica et Biophysica Acta, 2013, 1834(12): 2546 – 2553.
24. Structural glycobiology: applications in cancer research.
Inka Brockhausen, Yin Gao, CRC Press, Taylor & Francis Group (Print ISBN: 978-1-4398-5460-0), 2012
会议：
(1) Yin Gao, Scott Strum, Bin Liu, John S. Schutzbach, Tatyana N. Druzhinina, Natalia S. Utkina, Vladimir I. Torgov, Walter A. Szarek, Lei Wang and Inka Brockhausen, "O-antigen synthesis in enterohaemorrhagic Escherichia coli serotype O157: characterization of a novel glucosyltransferase", Society for Glycobiology Annual Meeting, Seattle, WA, United States, Nov 9 – 12, 2011. (Oral).
(2）Yin Gao, Catherine Robbe-Masselot, Gregory Lee and Inka Brockhausen, “Structures of Carbohydrate-associated epitope on CA215 expressed in Ovarian and Cervical cancer cell lines and proposed Biosynthetic Pathways”, 244th ACS National Meeting & Exposition, Philadelphia, PA, United States, Aug 17 – 23, 2012. (Oral).
(3) Yin Gao and Harry W. Duckworth, “The role of 3 AA side chains in the function of Escherichia coli citrate synthase”, The 91st Canadian Chemistry Conference and Exhibition, Edmonton, Alberta, Canada, May 24 – 28, 2008. (Poster).
(4) Yin Gao and Inka Brockhausen, “Glycosylation pathways of human prostate cancer cells”, 20th International Symposium on Glycoconjugates, San Juan, Puerto Rico, United States, Nov 29 – Dec 4, 2009. (Poster).
(5) Yin Gao, Changchang Xu, Karen J. Rees-Milton, Inka Brockhausen and Tassos A. Anastassiades, “Glycosyltransferases and acyltransferases in bone and joint disease”, Canadian Connective Tissue Conference, Toronto, Ontario, Canada, June 3 – 5, 2010. (Poster).
(6) Yin Gao, Pi-Wan Cheng, Yifan Wang, Tassos A. Anastassiades and Inka Brockhausen, “The characteristic glycosylation potential of human prostate cancer cells”, Society for Glycobiology Annual Meeting, St. Petersburg, Florida, United States, Nov 7 – 10, 2010. (Poster).
(7) Yin Gao, Scott Strum, Bin Liu, John S. Schutzbach, Tatyana N. Druzhinina, Natalia S. Utkina, Vladimir I. Torgov, Walter A. Szarek, Lei Wang and Inka Brockhausen, "Characterization of a novel glucosyltransferase WbdN from Escherichia coli seroptype O157", 21st International Symposium on Glycoconjugates, Vienna, Austria, Aug 21 – 26, 2011. (Poster).
(8) Yin Gao, Jason Z. Vlahakis, Walter A. Szarek and Inka Brockhausen, "Imidazolium compounds: A new generation of galactosyltransferase inhibitors", Society for Glycobiology Annual Meeting, Seattle, WA, United States, Nov 9 – 12, 2011. (Poster).
(9) Inka Brockhausen, Yin Gao, Bin Liu, Jason Z. Vlahakis, Walter A. Szarek and Lei Wang, “O-antigen synthesis in enterohaemorrhagic Escherichia coli: Characterization of novel glycosyltransferases”, International Symposium on Glycosyltransferases, Hannover, Germany, June 5 – 9, 2012. (Poster).
(10) Yin Gao, Catherine Robbe-Masselot, Gregory Lee and Inka Brockhausen, “Structures of Carbohydrate-associated Epitope on CA215 Expressed in Ovarian and Cervical Cancer Cell lines”, International Symposium on Glycosyltransferases, Hannover, Germany, June 5 – 9, 2012. (Poster).
(11) Inka Brockhausen, Yin Gao, Bin Liu, Jason Z. Vlahakis, Walter A. Szarek and Lei Wang, “O-antigen synthesis in enterohaemorrhagic Escherichia coli: Characterization of novel glycosyltransferases”, 243th ACS National Meeting & Exposition, San Diego, CA, United States, March 25 – 29, 2012. (Poster).
(12) Yin Gao, Jiasheng Lu, Xianqi Kong and Gang Wu, “Synthesis of myoglobin-HNO adducts”, MOOT XXVI NMR Symposium, Kingston, ON, Canada, Oct 25 – 27, 2013. (Poster).
书籍著作: （1）Yin Gao, Anna Vinnikova, Inka Brockhausen, Functional identification of bacterial glucosyltransferase WbdN, Methods. Mol. Biol., 2013, 1022: 199 – 214, Springer Science+Business Media New York, 2013
（2）Inka Brockhausen, Yin Gao, Chapter 8. Structural glycobiology: applications in cancer research, CRC Press, Taylor & Francis Group (Print ISBN: 978-1-4398-5460-0), 2012
发明专利：
1. 一种透明质酸衍生化的非兹体抗炎抗癌药物及其制备方法和应用[2018107668977] 中国专利
2. 一种具有靶向性和抗炎活性的氟化透明质酸衍生物及其制备方法和应用[2018107669077] 中国专利
3. N-Butyrylated hyaluronic acid for hyperuricemia and gouty arthritis [US62/640,910] 美国专利
4. N-Butyrylated hyaluronic acid formulated gel for wound healing [US62/815,782] 美国专利
承担的基金项目：
1. 国家自然科学青年基金（2018-2020）
2. 吉林省科技厅科技发展项目（2017-2019）
3. 吉林省人才项目（2016-2018）
4. 吉林省教育厅项目（2018-2019,2021-2022）
5. 吉林省科学技术协会项目（2018）
6. 吉林省发改委产业技术研究与开发项目（2019-2020）
7. 吉林省科技发展计划项目-国际科技合作（2020-2022）
|
