DOI

https://doi.org/10.25772/K0TS-PR38

Defense Date

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biochemistry

First Advisor

Charles Chalfant

Abstract

Lipidomics, a rapidly developing field of study, focuses on the classification and quantitation of lipid species. Lipidomics has emerged in the forefront of scientific research due to the key roles that lipids play in metabolism, cancer, and disease. Using mass spectrometry as a tool for analysis, understanding the role eicosanoids and sphingolipids play has advanced rapidly. Being able to observe these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and identification of eicosanoid and sphingolipid biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. In the studies herein, we developed targeted mass spectrometric methods to identify lipids of interest in inflammatory disease signaling. We further used lipidomics to identify biomarkers in a clinical trial involving patients diagnosed with pre-eclampsia, discovering that ceramide-1-phosphate, a lipid involved in the initiation of inflammation, was significantly decreased in the plasma of patients who developed pre-eclampsia. Additionally, lipidomic studies were used to elucidate the mechanism of the cPLA2α/C1P interaction, in which the binding of C1P to of cPLA2α was ablated (cPLA2α KI) resulting in resistance to sepsis and increased wound closure rate of cPLA2α KI mice. These studies show how useful lipidomics coupled with mass spectrometry can be in studying inflammatory diseases regulated by lipid signaling.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-4-2019

Available for download on Monday, December 02, 2024

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