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 cancer
a. Breast cancer
b. Glioma and glioblastoma
- Extracellular matrix structure and neurological diseases
b. Parkinson’s disease
- Method for proteomics and glycomics from tissue slides
- Glycoproteomics of influenza virus
Margaret Downs—Graduate Student
Manveen Sethi – Instructor
Deborah Chang – Graduate Student
William Hackett – Graduate Student, Bioinformatics
- 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
- Raghunathan, R.; Sethi, M. K.; Klein, J. A.; Zaia, J. Proteomics, glycomics, and glycoproteomics of matrisome molecules. Mol Cell Proteomics 2019, . Pubmed Link
- Raghunathan, R.; Sethi, M.; Zaia, J. On-slide tissue digestion for mass spectrometry based glycomic and proteomic profiling. MethodsX 2019, . Pubmed Link
- Klein, J. A.; Zaia, J. psims – A declarative writer for mzML and mzIdentML for Python. Mol Cell Proteomics 2019, 18, 571-575. Pubmed Link
- Klein, J.; Zaia, J. glypy: An Open Source Glycoinformatics Library. J Proteome Res 2019, 18, 3532-3537. 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
- 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 Proteomics 2018, 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 Proteomics 2018, 17, 1578-1590. Pubmed Link
- Klein, J.; Carvalho, L.; Zaia, J. Application of Network Smoothing to Glycan LC-MS Profiling. Bioinformatics 2018, 34, 3511-3518. Pubmed Link
- Khatri, K.; Pu, Y.; Klein, J. A.; Wei, J.; Costello, C. E.; Lin, C.; Zaia, J. Comparison of Collisional and Electron-Based Dissociation Modes for Middle-Down Analysis of Multiply Glycosylated Peptides. J Am Soc Mass Spectrom 2018, 29, 1075-1085. 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 Proteomics 2018, 17, 1448-1456. Pubmed Link
- Sethi, M. K.; Zaia, J. Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease. Anal Bioanal Chem 2017, 409, 379-394. Pubmed Link
- Khatri, K.; Klein, J. A.; Zaia, J. Use of an informed search space maximizes confidence of site-specific assignment of glycoprotein glycosylation. Anal Bioanal Chem 2017, 409, 607-618. Pubmed Link
- Khatri, K.; Klein, J. A.; Haserick, J.; Leon, D. R.; Costello, C. E.; McComb, M. E.; Zaia, J. Microfluidic capillary electrophoresis-mass spectrometry for analysis of monosaccharides, oligosaccharides and glycopeptides. Anal. Chem. 2017, 89, 6645-6655. Pubmed Link
- Hu, H.; Khatri, K.; Zaia, J. Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev 2017, 36, 475-498. Pubmed Link