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My clinical and research interests are in congenital heart disease (CHD). Patients with CHD are the fastest growing population of adults with heart disease. Over the past few decades, new surgical interventions have dramatically increased the life expectancy of children with CHD. However, adults with CHD have a higher burden of heart-rhythm abnormalities and heart failure. These long-term consequences are even more evident in patients with complex congenital heart disease such as patients with single ventricle physiology or Fontan circulation. My previous research has shown that patients with Fontan circulation have chronically elevated proinflammatory cytokines that contributes to their late-term consequences. In addition to inflammation genetic mutations drive CHD pathology, and it is becoming evident that these mutations are complex and involve multiple environmental factors. The impact of these mutations in a post-developmental heart in the presence of inflammation is unknown. My research investigates the interaction between inflammation and genetic mutations associated with CHD in causing arrhythmias and heart failure. My laboratory uses induced pluripotent stem cells (iPSCs) in combination with CRISPR/Cas9 technology, to generate cell lines with unique complex mutations in NOTCH1, a receptor protein implicated in numerous CHD. Using patient derived iPSCs with NOTCH1 mutations in combination with genetically engineered iPSCs, I am interested in identifying external factors such as inflammatory cytokines that can contribute to the morbidity and mortality of CHD patients. My long-term goal is to identify novel drugs and therapies that can mitigate such detrimental physiologic sequalae.
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