Glycosaminoglycan glycomics

Heparan sulfate (HS) present on cell surfaces may be remodeled by extracellular sulfatase enzymes (Sulfs). These enzymes remove a fraction of the 6-O-sulfate groups on HS, thereby altering the manner in which the chains bind to protein partners. The loss of 6-O-sulfate groups alters cell responses to growth factors signaling through binding to HS, including Wnts, bone morphogenic proteins and fibroblastic growth factors. The question remains regarding the HS sequence context for Sulf recognition and activity, as well as the differences associated with different cellular phenotypes. We investigated remodeling of HS chains by Sulf2 at the disaccharide level. The results demonstrated that Sulf2 acts in a different manner at the chain non-reducing end, relative to the interior regions of the chain.

  • Wu, J.; Wei, J.; Chopra, P.; Boons, G. J.; Lin, C.; Zaia, J. Sequencing Heparan Sulfate Using HILIC LC-NETD-MS/MS. Anal. Chem. 2019, 91, 11738-11746. Pubmed Link
  • Wei, J.; Wu, J.; Tang, Y.; Ridgeway, M. E.; Park, M. A.; Costello, C. E.; Zaia, J.; Lin, C. Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS. Anal. Chem. 2019, 91, 2994-3001. Pubmed Link
  • Wu, J.; Wei, J.; Hogan, J. D.; Chopra, P.; Joshi, A.; Lu, W.; Klein, J.; Boons, G. J.; Lin, C.; Zaia, J. Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides. J Am Soc Mass Spectrom 2018, 29, 1262-1272. Pubmed Link
  • Chen, J.; Kawamura, T.; Sethi, M. K.; Zaia, J.; Repunte-Canonigo, V.; Sanna, P. P. Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse. Sci Rep 2017, 7, 13931. Pubmed Link
  • Zaia, J.; Khatri, K.; Klein, J. A.; Shao, C.; Sheng, Y.; Viner, R. Complete Molecular Weight Profiling of Low Molecular Weight Heparins Using Size Exclusion Chromatography-Ion Suppressor-High Resolution Mass Spectrometry. Anal. Chem. 2016, 88, 10654-10660. Pubmed Link
  • Tykesson, E.; Mao, Y.; Maccarana, M.; Pu, Y.; Gao, J.; Lin, C.; Zaia, J.; Westergren-Thorsson, G.; Ellervik, U.; Malmstrom, L.; Malmstrom, A. Deciphering the mode of action of the processive polysaccharide modifying enzyme dermatan sulfate epimerase 1 by hydrogen-deuterium exchange mass spectrometry. Chemical Science 2016, 7, 1447-1456. Pubmed Link
  • Huang, Y.; Mao, Y.; Zong, C.; Lin, C.; Boons, G.; Zaia, J. Discovery of a Heparan Sulfate 3-O-Sulfation Specific Peeling Reaction. Anal. Chem. 2015, 81, 592-600. Pubmed Link
  • Turi├ík, L.; Shao, C.; Meng, L.; Khatri, K.; Leymarie, N.; Wang, Q.; Pantazopoulos, H.; Leon, D. R.; Zaia, J. Workflow for Combined Proteomics and Glycomics Profiling from Histological Tissues. Anal. Chem. 2014, 86, 9670-9678. Pubmed Link
  • Huang, Y.; Mao, Y.; Buczek-Thomas, J. A.; Nugent, M. A.; Zaia, J. Oligosaccharide substrate preferences of human extracellular sulfatase sulf2 using liquid chromatography-mass spectrometry based glycomics approaches. PLoS ONE 2014, 9, e105143. Pubmed Link
  • Hu, H.; Huang, Y.; Mao, Y.; Yu, X.; Xu, Y.; Liu, J.; Zong, C.; Boons, G. J.; Lin, C.; Xia, Y.; Zaia, J. A Computational Framework for Heparan Sulfate Sequencing Using High-resolution Tandem Mass Spectra. Molecular & cellular proteomics : MCP 2014, 13, 2490-2502. Pubmed Link
  • Zaia, J. Glycosaminoglycan glycomics using mass spectrometry. Molecular & cellular proteomics : MCP 2013, 12, 885-92. Pubmed Link
  • Shi, X.; Shao, C.; Mao, Y.; Huang, Y.; Wu, Z. L.; Zaia, J. LC-MS and LC-MS/MS studies of incorporation of 34SO3 into glycosaminoglycan chains by sulfotransferases. Glycobiology 2013, 23, 969-979. Pubmed Link
  • Shao, C.; Shi, X.; White, M.; Huang, Y.; Hartshorn, K.; Zaia, J. Comparative glycomics of leukocyte glycosaminoglycans. The FEBS journal 2013, 280, 2447-2461. Pubmed Link
  • Shao, C.; Shi, X.; Phillips, J. J.; Zaia, J. Mass spectral profiling of glycosaminoglycans from histological tissue surfaces. Anal. Chem. 2013, 85, 10984-10991. Pubmed Link
  • Huang, Y.; Yu, X.; Mao, Y.; Costello, C. E.; Zaia, J.; Lin, C. De Novo Sequencing of Heparan Sulfate Oligosaccharides by Electron-Activated Dissociation. Anal. Chem. 2013, 85, 11979-11986. Pubmed Link
  • Gill, V. L.; Aich, U.; Rao, S.; Pohl, C.; Zaia, J. Disaccharide analysis of glycosaminoglycans using hydrophilic interaction chromatography and mass spectrometry. Anal. Chem. 2013, 85, 1138-45. Pubmed Link
  • Tran, T. H.; Shi, X.; Zaia, J.; Ai, X. Heparan Sulfate 6-O-endosulfatases (Sulfs) Coordinate the Wnt Signaling Pathways to Regulate Myoblast Fusion during Skeletal Muscle Regeneration. J. Biol. Chem. 2012, 287, 32651-32664. Pubmed Link
  • Thelin, M.; Svensson, K. J.; Shi, X.; Bagher, M.; Axelsson, J.; Isinger-Ekstrand, A.; van Kuppevelt, T. H.; Johansson, J.; Nilbert, M.; Zaia, J.; Belting, M.; Maccarana, M.; Malmstrom, A. Dermatan sulfate is involved in the tumorigenic properties of Esophagus Squamous Cell Carcinoma. Cancer Res. 2012, 72, 1943-1952. Pubmed Link
  • Shi, X.; Huang, Y.; Mao, Y.; Naimy, H.; Zaia, J. Tandem mass spectrometry of heparan sulfate negative ions: sulfate loss patterns and chemical modification methods for improvement of product ion profiles. J. Am. Soc. Mass Spectrom. 2012, 23, 1498-511. Pubmed Link
  • Maxwell, E.; Tan, Y.; Tan, Y.; Hu, H.; Benson, G.; Aizikov, K.; Conley, S.; Staples, G. O.; Slysz, G. W.; Smith, R. D.; Zaia, J. GlycReSoft: A Software Package for Automated Recognition of Glycans from LC/MS Data. PLoS ONE 2012, 7, e45474. Pubmed Link