Date of Award
Doctor of Clinical-Bioanalytical Chemistry
Barth Syndrome (BTHS) is an X-linked inborn error of metabolism (IEM) which manifests as a multi-systemic disease. One of the primary symptoms is dilated cardiomyopathy, and alongside the cardiovascular disease that arises, patients often experience metabolic abnormalities such as 3-methylglutaconic aciduria, growth retardation, and neutropenia. There has been a need for the development of a suitable in vitro modeling system which will accurately recapitulate the biochemical and physical nature of BTHS. The purpose of this project has been to develop a model for studying the biochemical pathogenesis of Barth Syndrome using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). To achieve this, groundwork was laid in developing differentiation methods for producing ventricular hiPSC-CMs from hiPSCs. Simultaneously, a group of methods utilizing mass spectrometry in the biochemical analysis of hiPSC-CMs was developed, and this has provided a novel platform for the detection of many metabolites for the purpose of analyzing the metabolic abnormalities due to BTHS. Biochemical characterization of hiPSC-CMs is a novel tool to be used in assessing biochemical abnormalities and has not previously been achieved.
House, Alisha J., "Biochemical Characterization Of Induced Pluripotent Stem Cell-Derived Cardiomyocytes As A Model Of Barth Syndrome" (2022). ETD Archive. 1331.