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Jingwei Zhang, Pharmsci graduate student (Li Lab), will be defending his PhD research thesis:

Development and Application of Mass Spectrometry Methods for Proteomics and Post-translational Modification Analysis

Abstract:

Mass spectrometry (MS) has emerged as a powerful analytical platform for comprehensive characterization of proteins and post-translational modifications (PTMs), benefiting from its high sensitivity, mass accuracy, resolution, and quantitative capability. Coupling liquid chromatography with tandem mass spectrometry (LC–MS/MS) enables large-scale profiling of complex biological samples and provides valuable molecular insights into disease mechanisms and biomarker discovery. This dissertation contributes to MS-based proteomics and PTM analysis through the development of innovative quantitative strategies and their applications to diverse biological and clinical systems.

First, an integrated high-abundance protein depletion and isobaric boosting strategy was developed to improve the detection and quantification of low-abundance serum N-glycopeptides. To further improve the analysis of low-abundance glycans, a Boost-SUGAR strategy was developed by combining 12-plex isobaric multiplex reagents for carbonyl-containing compounds (SUGAR) with an isobaric boosting channel. In addition to labeling-based approaches, an integrated data-independent acquisition (DIA) and parallel reaction monitoring (PRM) workflow was applied to quantitatively characterize human pancreatic tissues from individuals with type 1 diabetes (T1D), type 2 diabetes (T2D), and nondiabetic controls. To address quantitative interference associated with conventional isobaric reporterion quantification, an accurate and sensitive 7-plex DiLeuC complementary-ion strategy was developed for multiplexed proteomics. Finally, the capabilities of MS were extended beyond quantitative omics through the application of native electrospray ionization, ion mobility–mass spectrometry, and collision-induced dissociation to investigate interactions among amyloid β peptide, metal ions, and anions. Overall, this work advances quantitative mass spectrometry and provides versatile analytical platforms for disease mechanism investigation, biomarker discovery, and future biomedical research.