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July 16, 2024
Andrew Zhu, Pharmaceutical Sciences graduate student (Li Research Lab), will be defending his PhD research thesis:
Deep Structural Omics: Enhancing Precision to Facilitate Characterization of Molecular Mechanism of Diseases
Understanding the structural nuances of biomolecules is crucial for elucidating their roles in biological pathways and disease mechanisms. My thesis research is focused on the development of innovative multimodal mass spectrometry (MS) strategies to enhance the structural characterization of biomolecules. Key advancements include the creation of novel paired isobaric chiral reagents for high-throughput quantification of DL-amino acids, uncovering unique D-amino acids linked to Alzheimer’s disease and aging. Additionally, a “digestion-derivatization” strategy has been developed to determine the stereoconfiguration of protein lysine lactylation, revealing the dominance of L-lactylation induced by glycolysis. This dissertation research also advances lipidomics through high-resolution ion mobility MS, differentiating sn-position isomers of glycerophospholipids and revealing lipid remodeling pathways in neurodegenerative diseases. Furthermore, a novel method for dual-resolving C═C bond geometry and position in unsaturated fatty acids enables rapid quantification and molecular imaging, shedding light on polymicrobial interactions in pathogen physiology. These methodologies significantly enhance the depth and accuracy of biomolecular analysis, offering valuable insights into disease mechanisms and biological functions