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 aims 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.
- Development of mass spectral methods for structural analysis of glycosaminoglycans
- Studies of HS chain structure and patterns of expression according to spatial and temporal biological contexts
- Remodeling processes of HS by extracellular enzymes
- HS-growth factor binding
- Glycoproteomics of influenza virus hemagglutinin
Christina Dreyton – Postdoctoral Associate
Le Meng – Postdoctoral Associate
Manveen Sethi – Postdoctoral Associate
Deborah Chang – Graduate Student
Kshitij Khatri – Graduate Student
Joshua Klein – Graduate Student, Bioinformatics
J.D. Hogan – Graduate Student, Bioinformatics
Rekha Ragunathan – Graduate Student, Molecular & Translational Medicine
He H, Liu D, Lin H, Jiang S, Ying Y, Chun S, Deng H, Zaia J, Wen R, Luo Z. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein and has multiple functions. Biochim Biophys Acta. 2016 Jul; 1863(7 Pt A):1682-9. PMID: 27033522.
Khatri K, Klein JA, White MR, Grant OC, Leymarie N, Woods RJ, Hartshorn KL, Zaia J. Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions. Mol Cell Proteomics. 2016 Jun; 15(6):1895-912. PMID: 26984886.
Hu H, Khatri K, Zaia J. Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev. 2016 Jan 4. PMID: 26728195.
Tykesson E, Mao Y, Maccarana M, Pu Y, Gao J, Lin C, Zaia J, Westergren-Thorsson G, Ellervik U, Malmström L, Malmström A. Deciphering the Mode of Action of the Processive Polysaccharide Modifying Enzyme Dermatan Sulfate Epimerase 1 by Hydrogen-Deuterium Exchange Mass Spectrometry. Chem Sci. 2016 Feb 1; 7(2):1447-1456. PMID: 26900446.
Hu H, Khatri K, Klein J, Leymarie N, Zaia J. A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J. 2016 Jun; 33(3):285-96. PMID: 26612686.
Aoki-Kinoshita K, Agravat S, Aoki NP, Arpinar S, Cummings RD, Fujita A, Fujita N, Hart GM, Haslam SM, Kawasaki T, Matsubara M, Moreman KW, Okuda S, Pierce M, Ranzinger R, Shikanai T, Shinmachi D, Solovieva E, Suzuki Y, Tsuchiya S, Yamada I, York WS, Zaia J, Narimatsu H. GlyTouCan 1.0 – The international glycan structure repository. Nucleic Acids Res. 2016 Jan 4; 44(D1):D1237-42. PMID: 26476458.
Salanti A, Clausen TM, Agerbæk MØ, Al Nakouzi N, Dahlbäck M, Oo HZ, Lee S, Gustavsson T, Rich JR, Hedberg BJ, Mao Y, Barington L, Pereira MA, LoBello J, Endo M, Fazli L, Soden J, Wang CK, Sander AF, Dagil R, Thrane S, Holst PJ, Meng L, Favero F, Weiss GJ, Nielsen MA, Freeth J, Nielsen TO, Zaia J, Tran NL, Trent J, Babcook JS, Theander TG, Sorensen PH, Daugaard M. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Cancer Cell. 2015 Oct 12; 28(4):500-14. PMID: 26461094.
Huang Y, Mao Y, Zong C, Lin C, Boons GJ, Zaia J. Discovery of a heparan sulfate 3-O-sulfation specific peeling reaction. Anal Chem. 2015 Jan 6; 87(1):592-600. PMID: 25486437.
Reine TM, Kolseth IB, Meen AJ, Lindahl JP, Jenssen TG, Reinholt FP, Zaia J, Shao C, Hartmann A, Kolset SO. Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation. Diabetes Res Clin Pract. 2015 Jan; 107(1):46-53. PMID: 25467621.
Mao Y, Huang Y, Buczek-Thomas JA, Ethen CM, Nugent MA, Wu ZL, Zaia J. A liquid chromatography-mass spectrometry-based approach to characterize the substrate specificity of mammalian heparanase. J Biol Chem. 2014 Dec 5; 289(49):34141-51. PMID: 25336655.
Complete list can be found at BU Profiles