The manner in which a cell responds to many growth factor stimuli depends on interactions between glycosaminoglycans (GAGs), growth factors, and growth factor receptors. Extracellular matrix GAGs binds growth factors, creating morphogens gradients essential to tissue patterning. Because these events depend on the fine structure of the GAG chains present, regulation of GAG biosynthesis is a key factor for understanding normal and disease related cellular growth
The key to exploiting an understanding of GAG structure-function relationships for human disease therapy is to winnow oligosaccharide-protein binding patterns from heterogeneous biological preparations. Toward this end, we have developed mass spectral methods for GAGs that enable comparison of structures as a function of biological variables.
The long term research aims are (1) to develop a fundamental understanding of the manner in which glycosaminoglycan expression is varied according to the cellular growth environment related to human disease and (2) to identify HS chain structures useful as therapeutic targets.
New bioinformatics methods are essential to realizing these goals. The data produced using our methods are information rich and not amenable to manual interpretation. Further, the methods needed are distinct from those used in genomics and proteomics. We are developing bioinformatics methods appropriate for interpretation of structural data on glycosaminoglycans and other carbohydrates to identify targets for disease therapy.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Member, Bioinformatics Graduate Program, Boston University
- Center Faculty Member, Mass Spectrometry, Boston University School of Medicine
- Massachusetts Institute of Technology, PhD
- Bates College, BS
- Published on 11/25/2017
Wu ZL, Person A, Anderson M, Burroughs B, Tatge T, Khatri K, Zou Y, Wang L, Geders T, Zaia J, Sackstein R. Imaging specific cellular glycan structures using glycosyltransferases via click chemistry. Glycobiology. 2017 Nov 25. PMID: 29186441.
- Published on 10/24/2017
Chen J, Kawamura T, Sethi MK, Zaia J, Repunte-Canonigo V, Sanna PP. Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse. Sci Rep. 2017 Oct 24; 7(1):13931. PMID: 29066725.
- Published on 6/6/2017
Khatri K, Klein JA, Haserick JR, Leon DR, Costello CE, McComb ME, Zaia J. Microfluidic Capillary Electrophoresis-Mass Spectrometry for Analysis of Monosaccharides, Oligosaccharides, and Glycopeptides. Anal Chem. 2017 Jun 20; 89(12):6645-6655. PMID: 28530388.
- Published on 6/1/2017
Wu ZL, Huang X, Ethen CM, Tatge T, Pasek M, Zaia J. Non-reducing end labeling of heparan sulfate via click chemistry and a high throughput ELISA assay for heparanase. Glycobiology. 2017 Jun 01; 27(6):518-524. PMID: 28025251.
- Published on 3/30/2017
Glaskin RS, Khatri K, Wang Q, Zaia J, Costello CE. Construction of a Database of Collision Cross Section Values for Glycopeptides, Glycans, and Peptides Determined by IM-MS. Anal Chem. 2017 Apr 18; 89(8):4452-4460. PMID: 28323417.
- Published on 2/6/2017
Wu ZL, Huang X, Ethen CM, Tatge T, Pasek M, Zaia J. Non-reducing end labeling of heparan sulfate via click chemistry and a high throughput ELISA assay for heparanase. Glycobiology. 2017 Feb 06; 1-7. PMID: 28173134.
- Published on 11/22/2016
Liu Y, McBride R, Stoll M, Palma AS, Silva L, Agravat S, Aoki-Kinoshita KF, Campbell MP, Costello CE, Dell A, Haslam SM, Karlsson NG, Khoo KH, Kolarich D, Novotny MV, Packer NH, Ranzinger R, Rapp E, Rudd PM, Struwe WB, Tiemeyer M, Wells L, York WS, Zaia J, Kettner C, Paulson JC, Feizi T, Smith DF. The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data. Glycobiology. 2016 Nov 22. PMID: 27993942.
- Published on 10/17/2016
Zaia J, Khatri K, Klein J, 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 Nov 01; 88(21):10654-10660. PMID: 27709905.
- Published on 10/12/2016
Khatri K, Klein JA, Zaia J. Use of an informed search space maximizes confidence of site-specific assignment of glycoprotein glycosylation. Anal Bioanal Chem. 2017 Jan; 409(2):607-618. PMID: 27734143.
- Published on 10/5/2016
Dierker T, Shao C, Haitina T, Zaia J, Hinas A, Kjellén L. Nematodes join the family of chondroitin sulfate-synthesizing organisms: Identification of an active chondroitin sulfotransferase in Caenorhabditis elegans. Sci Rep. 2016 Oct 05; 6:34662. PMID: 27703236.
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