Glycomics is rapidly emerging as a new paradigm for biomarker discovery. Diseases as diverse as infection and cancer are known to involve changes in glycosylation. Glycans on cell surfaces are important for understanding nearly all cell surface interactions. They are key targets for drugs and may yield cell-specific therapeutics. In addition, they are also shed and can give indications of the changes in glycosylation associated with the disease. The study of glycosylation of cell surfaces is still in its infancy. The majority of the research has employed fluorescently labeled lectins providing few structural details. In this proposal, we will develop techniques to study surface glycans by using methods that release them specifically and examine them with high sensitivity. In the process, we will develop comprehensive methods to determine glycan structures and micoheterogeneity. To achieve these tasks, we will develop a high throughput method for glycomics analysis that will rapidly identify glycan structures. This goal would have seemed impossible given the complexity and the heterogeneity of glycan structures. However, we will develop a method with a constructed database at its core that will serve as template with descriptors including liquid chromatography retention time, accurate mass, and tandem mass spectrometry to identify individual glycan (or oligosaccharide) structures. The creation of this database will form the kernel of a comprehensive database will allow routine analysis of oligosaccharide possible. The development of methods for the rapid identification will significantly advance glycobiology research. Additionally, the analysis of glycans by liquid chromatography will provide a new method for biomarker discovery by allowing the analysis of structural isomers thereby increasing the richness of the compound pool.

Public Health Relevance

A method for the deep structural analysis of glycans on cell surface will be developed that will allow differentiation of specific cancer types based on their glycan profile. This research will lead to potentially new biomarkers for cancer-specific therapeutics.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01GM049077-20
Application #
8608532
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Davis
State
CA
Country
United States
Zip Code
95618
Park, Dayoung; Arabyan, Narine; Williams, Cynthia C et al. (2016) Salmonella Typhimurium Enzymatically Landscapes the Host Intestinal Epithelial Cell (IEC) Surface Glycome to Increase Invasion. Mol Cell Proteomics 15:3653-3664
Yang, Nan; Goonatilleke, Elisha; Park, Dayoung et al. (2016) Quantitation of Site-Specific Glycosylation in Manufactured Recombinant Monoclonal Antibody Drugs. Anal Chem 88:7091-100
Arabyan, Narine; Park, Dayoung; Foutouhi, Soraya et al. (2016) Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6:29525
Huang, Jincui; Guerrero, Andres; Parker, Evan et al. (2015) Site-specific glycosylation of secretory immunoglobulin A from human colostrum. J Proteome Res 14:1335-49
Ruhaak, L Renee; Lebrilla, Carlito B (2015) Applications of Multiple Reaction Monitoring to Clinical Glycomics. Chromatographia 78:335-342
Song, Ting; Aldredge, Danielle; Lebrilla, Carlito B (2015) A Method for In-Depth Structural Annotation of Human Serum Glycans That Yields Biological Variations. Anal Chem 87:7754-62
Dallas, David C; Guerrero, Andres; Parker, Evan A et al. (2015) Current peptidomics: applications, purification, identification, quantification, and functional analysis. Proteomics 15:1026-38
Park, Dayoung; Brune, Kristin A; Mitra, Anupam et al. (2015) Characteristic Changes in Cell Surface Glycosylation Accompany Intestinal Epithelial Cell (IEC) Differentiation: High Mannose Structures Dominate the Cell Surface Glycome of Undifferentiated Enterocytes. Mol Cell Proteomics 14:2910-21
Hong, Qiuting; Ruhaak, L Renee; Stroble, Carol et al. (2015) A Method for Comprehensive Glycosite-Mapping and Direct Quantitation of Serum Glycoproteins. J Proteome Res 14:5179-92
Ruhaak, L Renee; Taylor, Sandra L; Stroble, Carol et al. (2015) Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue. J Proteome Res 14:4538-49

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