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
Manveen Sethi – Postdoctoral Associate
Jiandong Wu – Postdoctoral Associate
Deborah Chang – Graduate Student
Joshua Klein – Graduate Student, Bioinformatics
J.D. Hogan – Graduate Student, Bioinformatics
Rekha Ragunathan – Graduate Student, Molecular & Translational Medicine
- 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
- 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
- Khatri, K.; Klein, J. A.; White, M. R.; Grant, O. C.; Leymarie, N.; Woods, R. J.; Hartshorn, K. L.; Zaia, J. Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions. Mol Cell Proteomics 2016, 15, 1895-912. Pubmed Link
- Hu, H.; Khatri, K.; Zaia, J. Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev 2016, . 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
- Turiák, 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
- Mao, Y.; Huang, Y.; Buczek-Thomas, J. A.; Ethen, C. M.; Nugent, M. A.; Wu, Z. L.; Zaia, J. A Liquid Chromatography-Mass Spectrometry-based Approach to Characterize the Substrate Specificity of Mammalian Heparanase. J Biol Chem 2014, 289, 34141-51. Pubmed Link
- Khatri, K.; Staples, G. O.; Leymarie, N.; Leon, D. R.; Turiák, L.; Huang, Y.; Yip, S.; Hu, H.; Heckendorf, C. F.; Zaia, J. Confident Assignment of Site-Specific Glycosylation in Complex Glycoproteins in a Single Step. J. Proteome Res. 2014, 13, 4347-4355. Pubmed Link
Complete list can be found at BU Profiles