Abstract

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.

  Funding Agency

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

  Institution

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

  Publications

Park, Diane Dayoung; Xu, Gege; Wong, Maurice et al. (2018) Membrane glycomics reveal heterogeneity and quantitative distribution of cell surface sialylation. Chem Sci 9:6271-6285
Ruhaak, L Renee; Xu, Gege; Li, Qiongyu et al. (2018) Mass Spectrometry Approaches to Glycomic and Glycoproteomic Analyses. Chem Rev 118:7886-7930
Kailemia, Muchena J; Xu, Gege; Wong, Maurice et al. (2018) Recent Advances in the Mass Spectrometry Methods for Glycomics and Cancer. Anal Chem 90:208-224
Galermo, Ace G; Nandita, Eshani; Barboza, Mariana et al. (2018) Liquid Chromatography-Tandem Mass Spectrometry Approach for Determining Glycosidic Linkages. Anal Chem 90:13073-13080
Kailemia, Muchena J; Wei, Wanghui; Nguyen, Khoa et al. (2018) Targeted Measurements of O- and N-Glycopeptides Show That Proteins in High Density Lipoprotein Particles Are Enriched with Specific Glycosylation Compared to Plasma. J Proteome Res 17:834-845
Wong, Maurice; Xu, Gege; Park, Dayoung et al. (2018) Intact glycosphingolipidomic analysis of the cell membrane during differentiation yields extensive glycan and lipid changes. Sci Rep 8:10993
Song, Ting; Chen, Peng; Stroble, Carol et al. (2018) Serum glycosylation characterization of osteonecrosis of the femoral head by mass spectrometry. Eur J Mass Spectrom (Chichester) 24:178-187
Phoomak, Chatchai; Silsirivanit, Atit; Park, Dayoung et al. (2018) O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1. Oncogene 37:5648-5665
Miyamoto, Suzanne; Stroble, Carol D; Taylor, Sandra et al. (2018) Multiple Reaction Monitoring for the Quantitation of Serum Protein Glycosylation Profiles: Application to Ovarian Cancer. J Proteome Res 17:222-233
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

Showing the most recent 10 out of 102 publications