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)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM049077-18A1
Application #
8297837
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
1993-05-01
Project End
2016-01-31
Budget Start
2012-05-01
Budget End
2013-01-31
Support Year
18
Fiscal Year
2012
Total Cost
$265,248
Indirect Cost
$76,923
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Park, Dayoung; Xu, Gege; Barboza, Mariana et al. (2017) Enterocyte glycosylation is responsive to changes in extracellular conditions: implications for membrane functions. Glycobiology 27:847-860
Kailemia, Muchena J; Park, Dayoung; Lebrilla, Carlito B (2017) Glycans and glycoproteins as specific biomarkers for cancer. Anal Bioanal Chem 409:395-410
Huang, Jincui; Kailemia, Muchena J; Goonatilleke, Elisha et al. (2017) Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM). Anal Bioanal Chem 409:589-606
Krishnan, Sridevi; Shimoda, Michiko; Sacchi, Romina et al. (2017) HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes. Sci Rep 7:43728
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
Ruhaak, L Renee; Kim, Kyoungmi; Stroble, Carol et al. (2016) Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients. J Proteome Res 15:1002-10
Miyamoto, Suzanne; Ruhaak, L Renee; Stroble, Carol et al. (2016) Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies Unusual Glycopeptides. J Proteome Res 15:3358-76
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
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
Underwood, Mark A; Gaerlan, Stephanie; De Leoz, Maria Lorna A et al. (2015) Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res 78:670-7

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