Zhang focuses on oncometabolite’s role in heart failure

Yuan Zhang, PhD, associate in Endocrinology and Metabolism, received a three-year, $231,000 Career Development Award from the American Heart Association. Zhang’s project, “2-Hydroxyglutate mediates cardiac remodeling induced by mitochondrial stress,” seeks to understand how cardiac metabolism affects heart function. Zhang is a member of the Abel Laboratory. This is the second of three AHA CDAs on which department faculty will serve as mentors.

Mitochondria is the main site for substrate metabolism in the heart, and this metabolism dysfunction is linked to the development of heart failure. As a result of metabolic stressors in heart failure models, researchers found increased levels of 2-hydroxglutarate (2HG), an oncometabolite found in multiple cancer types.

Zhang’s project will examine the mechanisms of increased 2HG as a result of cardiac metabolic stress. Furthermore, she and her colleagues will test to see if increased 2HG activates hypoxia signaling and induces cardiac hypertrophy. To test their hypothesis, the researchers will normalize 2HG levels in the mouse model and examine the cardiac function and hypoxia after viral induction in multiple heart failure models.

“With the results from the proposed experiments, we hope to determine the impact of 2HG in heart in the metabolic stress and general heart failure models,” Zhang said. “All of these results will provide critical insight into how changing the mitochondrial substrate metabolism in the heart may influence cardiac function in heart failure and deepen our understanding of the cardiovascular effects of cancer effects and treatments.”

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