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Wnt/_-Catenin Mediated Regulation Of Murine And Human Cardiac Electrophysiology And Arrhythmogenesis, Gang Li Aug 2020

Wnt/_-Catenin Mediated Regulation Of Murine And Human Cardiac Electrophysiology And Arrhythmogenesis, Gang Li

McKelvey School of Engineering Theses & Dissertations

Cardiac arrhythmias affects millions of Americans and can lead to sudden cardiac death, accounting for more than 300,000 deaths annually. Despite the vast knowledge available for cardiac disease and associated arrhythmias, very few effective therapies exist. Current interventions include cardioverter defibrillators and antiarrhythmic drugs targeting ion channels or the _-adrenergic pathway. In most acquired and inherited arrhythmias, molecular signaling pathways are perturbed. However, little is known about the underlying mechanism of how these signaling pathways regulate cardiac electrophysiology. Therefore, a better understanding of major signaling pathways governing cardiac development or dysregulated in cardiac disease could lead to novel therapeutics for …


Notch-Mediated Regulation Of Atrial Arrhythmogenesis, Catherine Lipovsky May 2020

Notch-Mediated Regulation Of Atrial Arrhythmogenesis, Catherine Lipovsky

Arts & Sciences Electronic Theses and Dissertations

Abnormalities in electrical impulse generation and/or propagation that affect the heartճ normal rhythm are extremely common. Clinically, cardiac arrhythmias are prevalent worldwide, yet the molecular mechanisms underlying their pathology remain largely unknown. Current treatments for arrhythmias primarily target symptoms rather than the underlying cause and these treatments have limited efficacy. The most common risk factor for developing an arrhythmia is a previous cardiac injury; however, the mechanisms underlying this are not well described. My thesis work has demonstrated that the Notch signaling pathway, which is crucial for cardiac patterning and development and is normally quiescent in adult cardiomyocytes (CMs), is …