B.A. in Chemistry, Carleton College, 2019
Some of the most severe forms of cardiovascular disease include genetic mutations affecting the proteome of cardiomyocytes through the co-transcriptional process of alternative splicing. Alternative splicing is a great source of proteomic diversity and can tune the mechanical, structural, signaling, and metabolic properties of the heart. It is a normal physiological process that is essential for development, cellular differentiation, and physiological adaptation to external stimuli such as physiological cardiac hypertrophy in response to exercise, pregnancy, or in the case of the Burmese Python, feeding. In response to a meal, the Burmese python heart grows in mass by approximately 40% within 2-3 days after feeding, before regressing to its original size within the following week. My project seeks to use the Burmese python as a model in which I will identify how splicing of various transcripts changes in physiological cardiac hypertrophy and regression, as well as the protein factors responsible for these splicing events. Targeted genomic approaches (such as gene knockout/knockdown) can then be carried out in an iPSC-derived cardiomyocyte model of hypertrophy to better define the roles of individual factors in cardiac remodeling. Findings from these studies can be compared with other models of physiological hypertrophy (exercise, pregnancy), as well as with pathological states such as hypertrophic cardiomyopathy (HCM). This will allow for insight into how alternative splicing differs in physiological and pathological cardiac remodeling and will hopefully lead to the improved diagnosis/treatment of cardiac diseases such as HCM in the future.