Andrew Landstrom, MD, PhD
Determining the Role of PRDM16 in Divergent Types of Pediatric Cardiomyopathy
Duke University, Durham, NC
2019-2020 Amount Awarded (CCF/AAP Early Career Research Grant) – $50,000
The development of heart muscle disease, or cardiomyopathy, in infants and young children is associated with a high rate of death or the need for a heart transplant. While a number of different types of cardiomyopathies have been identified, little is known about the molecular drivers that may predispose a child to one, more potentially multiple, forms of cardiomyopathic disease. This lack of understanding greatly limits the medical community's ability to develop drugs targeted at preventing, or potentially reversing, cardiomyopathy. The goal is to identify these genetic and molecular drivers of disease so that novel therapeutics can be identified. The Landstrom lab research team has identified a novel mutation in a gene PRDM16 which is associated with infant-onset cardiomyopathy which can serve as a model for understanding both dilated cardiomyopathy and hypertrophic cardiomyopathy. Specifically, induced-pluripotent stem cells will be utilized to create cardiac myocytes hosting this genetic defect. A mouse knock-in model will be used to explore how this mutation may alter TGFb signaling within the heart. Further, the possibility that divergent types of TGFb signaling may result in distinct forms of cardiomyopathy will be explored. If successful, this study will yield new insights into the causes of cardiomyopathic disease in children.