We will develop the methods and tools that will profile glycans in human fluids to enable the discovery of markers for diseases. Cancer is a disease known to accompany aberrant glycosylation. Glycoproteins shed by diseased cells will be harvested for their glycan content and profiled to obtain disease markers. This approach represents a new paradigm for disease marker discovery. It will focus primarily on the glycans as disease markers while neglecting, at first, the identity of the associated proteins. This approach will be multifaceted and primarily glycocentric;it contrasts and complements the proteome-centered approaches currently under extensive investigations. In this process, we will develop a set of mass spectrometry-based tools for clinical glycomics. These tools will be used to observe changes in glycosylation of diseases in two human fluids, sera and tear. The fluids are chosen by the needs of our collaborator in diseases that include ovarian cancer and ocular rosacea but will have direct implications in breast cancer and prostate cancer for sera and other dry eye diseases for tear fluids. While disease markers will be the future outcome of these studies, they will not be the only focus of this project. Instead we will also develop the tools that will be used by our collaborators to discover markers for these diseases and lay the foundation for the use of mass spectrometry in clinics for glycomic analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM049077-17
Application #
7753848
Study Section
Special Emphasis Panel (ZRG1-BCMB-M (10))
Program Officer
Edmonds, Charles G
Project Start
1993-05-01
Project End
2010-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
17
Fiscal Year
2010
Total Cost
$236,044
Indirect Cost
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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