The manner in which a cells respond to growth factor stimuli depends on interactions among cell surface receptors, growth factor ligands, and extracellular matrix molecules. Cell surface and extracellular matrix molecules bind growth factors, creating morphogens gradients essential to tissue patterning. Cell surface proteoglycans catalyzes the binding of growth factors to receptors, initiating downstream signaling. These events depend on the fine structure of in a given spatial and temporal context in normal and disease biochemistry.
The key to exploiting an understanding of cell surface and extracellular matrix molecular structure-function relationships for human disease therapy is to determine their roles in normal and diseased tissue. Toward this end, we have developed mass spectral methods for glycomics, proteomics, and glycoproteomics that enable comparison of structures as a function of biological variables.
We aim to develop a fundamental understanding of the manner in which cell surface and extracellular matrix molecular structure varies according to disease mechanisms. We have collaborative projects concerning cancer, neurological diseases, and viral disease. Our effort is divided among methods development, applied biochemistry, and bioinformatics.
A summary of current research projects follows.
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- Mass spectral and bioinformatics methods for sequencing glycosaminoglycans
- Bioinformatics methods for glycoproteomics and glycomics
- Extracellular matrix structure and neurological diseases
- Methods for glycoproteomics from brain tissue
- Glycoproteomics of viral proteins
Laboratory members
Mary Rachel Stimson – Graduate student, Bioinformatics
Representative Publications
- Xia, C.; Mernie, E.; Zaia, J.; Costello, C. E.; Lin, C. Accurate Collisional Cross Section Measurement by Multipass Cyclic Ion Mobility Spectrometry. Anal. Chem. 2024, 96, 11959-11968. Pubmed Link
- Sethi, M. K.; Maccioni, R.; Hogan, J. D.; Kawamura, T.; Repunte-Canonigo, V.; Chen, J.; Zaia, J.; Sanna, P. P. Comprehensive Glycomic and Proteomic Analysis of Mouse Striatum and Lateral Hypothalamus Following Repeated Exposures to Cocaine or Methamphetamine. Mol Cell Proteomics 2024, 23, 100803. Pubmed Link
- Li, R.; Xia, C.; Wu, S.; Downs, M. J.; Tong, H.; Tursumamat, N.; Zaia, J.; Costello, C. E.; Lin, C.; Wei, J. Direct and Detailed Site-Specific Glycopeptide Characterization by Higher-Energy Electron-Activated Dissociation Tandem Mass Spectrometry. Anal. Chem. 2024, 96, 1251-1258. Pubmed Link
- Klein, J.; Carvalho, L.; Zaia, J. Expanding N-glycopeptide identifications by modeling fragmentation, elution, and glycome connectivity. Nat Commun 2024, 15, 6168. Pubmed Link
- Hackett, W. E.; Chang, D.; Carvalho, L.; Zaia, J. RAMZIS: a bioinformatic toolkit for rigorous assessment of the alterations to glycoprotein composition that occur during biological processes. Bioinform Adv 2024, 4, vbae012. Pubmed Link
- Wong, T. L.; Mooney, B. P.; Cavallero, G. J.; Guan, M.; Li, L.; Zaia, J.; Wan, X. F. Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. J Proteome Res 2023, 22, 62-77. Pubmed Link
- Wei, J.; Papanastasiou, D.; Kosmopoulou, M.; Smyrnakis, A.; Hong, P.; Tursumamat, N.; Klein, J. A.; Xia, C.; Tang, Y.; Zaia, J.; Costello, C. E.; Lin, C. De novo glycan sequencing by electronic excitation dissociation MS(2)-guided MS(3) analysis on an Omnitrap-Orbitrap hybrid instrument. Chem Sci 2023, 14, 6695-6704. Pubmed Link
- Liu, X.; Halvorsen, S.; Blanke, N.; Downs, M.; Stein, T. D.; Bigio, I. J.; Zaia, J.; Zhang, Y. Progressive mechanical and structural changes in anterior cerebral arteries with Alzheimer’s disease. Alzheimer’s research & therapy 2023, 15, 185. Pubmed Link
- Downs, M.; Curran, J.; Zaia, J.; Sethi, M. K. Analysis of complex proteoglycans using serial proteolysis and EThcD provides deep N- and O-glycoproteomic coverage. Anal Bioanal Chem 2023, 415, 6995-7009. Pubmed Link
- Dasgupta, S.; Zaia, J. Antiracism in biomolecular research. Anal Bioanal Chem 2023, 415, 6611-6613. Pubmed Link
- Wu, J.; Chopra, P.; Boons, G. J.; Zaia, J. Influence of saccharide modifications on heparin lyase III substrate specificities. Glycobiology 2022, 32, 208-217. Pubmed Link
- Downs, M.; Sethi, M. K.; Raghunathan, R.; Layne, M. D.; Zaia, J. Matrisome changes in Parkinson’s disease. Anal Bioanal Chem 2022, 414, 3005-3015. Pubmed Link
- Chang, D.; Klein, J.; Hackett, W.; Nalehua, M. R.; Wan, X. F.; Zaia, J. Improving statistical certainty of glycosylation similarity between influenza A virus variants using data-independent acquisition mass spectrometry. Mol Cell Proteomics 2022, , 100412. Pubmed Link