Proteoglycans are proteins glycosylated with glycosaminoglycans as well as other glycan classes. These molecules surround neurons and glial cells and form organized extracellular lattices. Because such lattices control the brain physiological microenvironment, proteoglycans are essential to both normal and disease mechanisms. Much of what is known about proteoglycan glycosylation derives from classical biochemical studies and immune-histology. Thus, while biomedical scientists have a general picture of proteoglycan structure, we lack an understanding of how glycosylation changes in association with neurological disease mechanisms.
We have developed analytical methods for analysis of glycan classes and proteins from histological slides. I will discuss applications of these methods to studies of brain aging, Parkinson’s disease, and glioblastoma.
Dr. Joseph Zaia, Ph. D. is a Professor in the Dept. of Biochemistry, Cell Biology and Genomics and Associate Director of the Center for Biomedical Mass Spectrometry (CBMS) on the Boston University Medical Campus (www.bumc.bu.edu/BUCBM). His primary research interest concerns structural biochemistry of proteoglycans and glycoproteins. He has extensive experience with methods for compositional analysis of glycosaminoglycan (GAG) oligosaccharides using liquid chromatography-mass spectrometry and sequencing using tandem mass spectrometry. His group has pioneered methods for analysis of GAGs from cultured cells, wet tissue, and histological slides from vertebrate and invertebrate sources. He has used these methods to study tissue-specific patterns of expression of heparan sulfate, activity of extracellular Sulf enzymes and mammalian heparanase. He has also developed bioinformatics software for interpretation glycan and glycopeptide liquid chromatography-mass spectrometry data.
Dr. Zaia collaborates widely with investigators regarding roles of proteoglycan and glycoprotein expression in human diseases. He organized an American Society for Mass Spectrometry tutorial on glycomics and glycoproteomics and participates regularly in short courses on these topics at international conferences. He organized an Association of Biomolecular Resource Facilities interlaboratory study on protein glycosylation and is a member of the Minimum Information Required for a Glycomics Experiment working group.
1. Khatri, K., et al., Comparison of collisional and electron-based dissociation modes for glycopeptide analysis. Journal of the American Society for Mass Spectrometry, 2018. accepted.
2. Sethi, M.K. and J. Zaia, Extracellular matrix proteomics in schizophrenia and Alzheimer's disease. Anal Bioanal Chem, 2017. 409(2): p. 379-394.
3. Khatri, K., J.A. Klein, and J. Zaia, Use of an informed search space maximizes confidence of site-specific assignment of glycoprotein glycosylation. Anal Bioanal Chem, 2017. 409(2): p. 607-618.
4. Khatri, K., et al., Microfluidic capillary electrophoresis-mass spectrometry for analysis of monosaccharides, oligosaccharides and glycopeptides. Anal Chem, 2017. 89(12): p. 6645-6655.
5. Hu, H., K. Khatri, and J. Zaia, Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev, 2017. 36(4): p. 475-498.
6. Chen, J., et al., Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse. Sci Rep, 2017. 7(1): p. 13931.
7. Zaia, J., et al., Complete Molecular Weight Profiling of Low Molecular Weight Heparins Using Size Exclusion Chromatography-Ion Suppressor-High Resolution Mass Spectrometry. Anal Chem, 2016. 88(21): p. 10654-10660.
8. Tykesson, E., et al., 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: p. 1447-1456.
9. Khatri, K., et al., Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions. Mol Cell Proteomics, 2016. 15(6): p. 1895-912.
10. Huang, Y., et al., Discovery of a Heparan Sulfate 3-O-Sulfation Specific Peeling Reaction. Anal Chem, 2015. 81(1): p. 592-600.
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