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Development and Application of Novel Glycan-Specific Reagents to Facilitate Early detection of epithelial ovarian cancer.

Keywords: epithelial ovarian cancer, mass spectrometry, glycans, plasma proteins, glycan-specific tags, biomarkers

Contact: David C. Muddiman
Phone: (919) 513-0084
North Carolina State University at Raleigh

Description (provided by applicant): Mass spectrometry is an extraordinarily powerful bio-analytical technique that has had a profound impact on our molecular understanding of human health and disease. Major advances in mass analyzer technology, dissociation techniques, and ionization methods are largely attributed to the central role that mass spectrometry plays in the field of systems biology. While mass spectrometry has evolved over the last century into a highly effective analytical tool, there are still opportunities for new advances to be made allowing an even more diverse array of biological questions to be addressed. This proposal is centered on the development and characterization of novel glycan-specific tags for biological mass spectrometry that facilitate the relative quantification of glycans cleaved from plasma proteins with increased ion abundance. The short-term objective of this proposal is to develop these novel tags and then test them using the avian model of spontaneous epithelial ovarian cancer. These results will provide a solid bio-analytical technology foundation from which our newly developed chemical tags can be applied to achieve the long-term objective of effectively elucidating glycan biomarkers for the early detection of epithelial ovarian cancer in women. Public Description of Proposed Research Mass spectrometry (MS), the science related to the ""weighing of molecules"", has had a profound impact on the study of human health and disease including cancer, heart disease, neural development, and auto-immune diseases. However, front-end chemistries for MS-based glycomics will be exploited to dramatically improve the ability of MS to detect and quantify glycans cleaved from plasma proteins. This will allow a more diverse array of contemporary biomedical questions to be addressed including the quantification of diagnostic and prognostic biomarkers. This proposal is squarely centered on the elucidation of a glycan-specific biomarker(s) for the early detection of epithelial ovarian cancer.

PUBLIC HEALTH RELEVANCE: This proposal seeks support to develop and apply novel tags that will facilitate both global and targeted quantitative mass spectrometric analysis of N-linked glycans with significantly improved limits-of-detection. Once synthesized, the novel tags and ancillary methods will concurrently be applied to the experimental chicken model of spontaneous epithelial ovarian cancer for comparative analysis (i.e., biomarker discovery) and fully disseminated to the glycomics research community. The long-term application of these novel tags, as developed in our laboratory for this study, will be their use to elucidate glycan biomarkers for the early detection of epithelial ovarian cancer.

Walker et al, Systematic Comparison of reverse phase and hydrophilic interaction liquid chromatography platforms for the analysis of N-linked glycans, Analytical Chem, Oct 2012


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