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Northeastern University

1. Gbormittah, Francisca Owusu. Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples.

Degree: PhD, Department of Chemistry and Chemical Biology, 2015, Northeastern University

The development of analytical technologies to investigate the glycoproteome of clinical relevant samples has improved over the last 10 years. These new developments aim to improve the identification and quantification of disease-specific glyco-biomarkers, which are present at low amounts in biological matrices. Glyco-biomakers have the potential to significantly contribute to cancer discovery studies in specific areas such as; early diagnosis, prognosis, monitor cancer recurrence and improve the low survival rate of cancer. In this thesis, we focused on the development and application of novel liquid affinity chromatography fractionation platforms integrated with nano-LC-MS/MS to characterize and quantify the glycoproteome as well as selected glyco-biomarker candidates of cancer samples.; In chapter 1, brief background information covering glycoproteomics and glyco-biomarker discovery studies is presented. Specifically, protein glycosylation process and how the field of `omics', which includes glycoproteomics, have revolutionized clinical glyco-biomarkers discovery are discussed. Further, various disease models, current sample fractionation strategies and analytical methodologies involved in glyco-biomarker development pipeline and their significance as well as their short falls are described. Reviewing biomarker validation and current bio-infomatics tools utilized in glycoproteomics discovery studies concludes chapter 1.; Chapter 2 details the development of a novel multi-dimensional affinity liquid chromatography fractionation approach that combines the depletion of the top 12 abundant proteins and multi-lectin fractionation of the human plasma. Evaluating and validating the reproducibility, specificity and overall recoveries of the platform demonstrated the suitability of the developed method in glyco-biomarker discovery studies of clinical samples. After establishing this robust platform, it was applied in chapter 3 to comprehensively study the global glycoproteome profile of clear cell renal cell carcinoma plasma (ccRCC) samples to identify and characterize potential biomarkers for early detection of the disease. During this study, protein abundance alterations as well as glycan shifts were investigated to understand the sub-proteome of ccRCC.; Chapter 4 focuses on the structural characterization of a glycoprotein (clusterin) that was identified during the ccRCC biomarker discovery studies. Clusterin has been implicated in ccRCC cancer progression however; its structure and biological function(s) are not yet well defined. Therefore, to have more structural insights into clusterin, the protein was immuno-affinity purified from ccRCC plasma followed by tandem mass spectrometry to profile glycoforms, N-glycosylation sites and quantify glycan amounts. We discovered that the levels of bi-antennary digalactosylated disialylated (A2G2S2) and core fucosylated bi-antennary digalactosylated disialylated (FA2G2S2) glycans differed significantly in the plasma of patients before and after curative nephrectomy of localized…

Subjects/Keywords: glycoproteomics; glyco-biomakers; Analytical Chemistry; Glycoproteins; Analysis; Biochemical markers; Diagnostic use; Liquid chromatography; Mass spectrometry; Pancreas; Cysts; Cancer; Diagnosis; Cancer; Prognosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Gbormittah, F. O. (2015). Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/d20005087

Chicago Manual of Style (16th Edition):

Gbormittah, Francisca Owusu. “Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples.” 2015. Doctoral Dissertation, Northeastern University. Accessed February 23, 2020. http://hdl.handle.net/2047/d20005087.

MLA Handbook (7th Edition):

Gbormittah, Francisca Owusu. “Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples.” 2015. Web. 23 Feb 2020.

Vancouver:

Gbormittah FO. Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples. [Internet] [Doctoral dissertation]. Northeastern University; 2015. [cited 2020 Feb 23]. Available from: http://hdl.handle.net/2047/d20005087.

Council of Science Editors:

Gbormittah FO. Advances in glycoproteomics and glyco-biomarker discovery studies:: development and application of liquid chromatography and mass spectrometry platforms to cancer samples. [Doctoral Dissertation]. Northeastern University; 2015. Available from: http://hdl.handle.net/2047/d20005087

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