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Title page for ETD etd-03202014-110420


Type of Document Dissertation
Author Hines, Kelly Marie
Author's Email Address kelly.m.hines@vanderbilt.edu
URN etd-03202014-110420
Title Biomolecular Signatures of Disease via Ion Mobility and Mass Spectrometry Techniques
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
John A. McLean Committee Chair
David E. Cliffel Committee Member
Donna J. Webb Committee Member
Eva M. Harth Committee Member
Keywords
  • asef2
  • breast cancer
  • wound healing
  • diabetes
  • ion mobility
  • mass spectrometry
  • biomolecular signatures
  • proteomics
  • metabolomics
Date of Defense 2014-03-11
Availability unrestricted
Abstract
Ion mobility-mass spectrometry (IM-MS) applies a gas-phase separation on the basis of structure prior to the MS, enabling separation of different types of biomolecules based on their gas-phase packing efficiencies. For complex sample analysis, IM-MS allows for a more holistic and untargeted approach requiring minimal sample preparation to the identification of the biomolecules differentially expressed between disease states. IM and MS work flows incorporating chromatographic separations and bioinformatics strategies are demonstrated for a range of biologically-driven applications. Analysis of wound fluid from a model system of wound healing in diabetes by IM-MS revealed protein, lipid and metabolite biomolecular species to distinguish diabetic and non-diabetic wound fluids. Profiling of extracts from human breast tissues by UPLC-IM-MS/MS identified a set of biomolecules which differentiated cancerous from non-cancerous or benign tissues, including species known to be differentially expressed in cancer but not often studied in the context of each other. Mapping the phosphorylation of the protein Asef2 using multiple proteolysis strategies identified a site which regulates cellular adhesion turnover and migration, processes necessary for cancer metastasis. These works exemplify the flexibility of IM and MS-based techniques for the characterization of biomolecular signatures of disease which span the range from metabolites to proteins.
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