Area of Interest Glycomics
Glycoproteomics
Neurological diseases
Viral diseases
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.
Mass spectral and bioinformatics methods for sequencing glycosaminoglycans
Bioinformatics methods for glycoproteomics and glycomics
Extracellular matrix structure and neurological diseases
Mary Rachel Stimson – Graduate student, Bioinformatics
Representative Publications
Muraoka, S.; DeLeo, A. M.; Sethi, M. K.; Yukawa-Takamatsu, K.; Yang, Z.; Ko, J.; Hogan, J. D.; Ruan, Z.; You, Y.; Wang, Y.; Medalla, M.; Ikezu, S.; Chen, M.; Xia, W.; Gorantla, S.; Gendelman, H. E.; Issadore, D.; Zaia, J.; Ikezu, T. Proteomic and biological profiling of extracellular vesicles from Alzheimer’s disease human brain tissues. Alzheimer’s & Dementia2020, doi: 10.1002/alz.12089. Pubmed Link
Klein, J. A.; Zaia, J. Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft. bioRxiv2020, , 2020.05.31.125302. Pubmed Link
Klein, J.; Zaia, J. Relative Retention Time Estimation Improves N-Glycopeptide Identifications By LC-MS/MS. J Proteome Res2020, 19, 2113-2121. Pubmed Link
Chang, D.; Hackett, W. E.; Zhong, L.; Wan, X. F.; Zaia, J. Measuring site-specific glycosylation similarity between influenza A virus variants with statistical certainty. Mol Cell Proteomics2020, . Pubmed Link
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
Klein, J. A.; Zaia, J. psims – A declarative writer for mzML and mzIdentML for Python. Mol Cell Proteomics2019, 18, 571-575. Pubmed Link
Chang, D.; Zaia, J. Why glycosylation matters in building a better flu vaccine. Mol Cell Proteomics2019, 18, 2348-2358. Pubmed Link
Raghunathan, R.; Polinski, N. K.; Klein, J. A.; Hogan, J. D.; Shao, C.; Khatri, K.; Leon, D.; McComb, M. E.; Manfredsson, F. P.; Sortwell, C. E.; Zaia, J. Glycomic and Proteomic Changes in Aging Brain Nigrostriatal Pathway. Molecular & Cellular Proteomics2018, 17, 1778-1787. Pubmed Link
Klein, J. A.; Meng, L.; Zaia, J. Deep sequencing of complex proteoglycans: a novel strategy for high coverage and site-specific identification of glycosaminoglycan-linked peptides. Mol Cell Proteomics2018, 17, 1578-1590. Pubmed Link
Klein, J.; Carvalho, L.; Zaia, J. Application of Network Smoothing to Glycan LC-MS Profiling. Bioinformatics2018, 34, 3511-3518. Pubmed Link
Hogan, J. D.; Klein, J. A.; Wu, J.; Chopra, P.; Boons, G. J.; Carvalho, L.; Lin, C.; Zaia, J. Software for peak finding and elemental composition assignment for glycosaminoglycan tandem mass spectra. Mol Cell Proteomics2018, 17, 1448-1456. Pubmed Link