John Carter Ralphe, MD

Human iPS Cells and ECT in the Study of Hypertrophic Cardiomyopathy
University of Wisconsin, Madison, WI
John Carter Ralphe, MD – $50,000

One of the most common genetic causes of hypertrophic cardiomyopathy (HCM) involves defects in a protein called cardiac myosin binding protein C (cMyBP-C). This protein makes up part of the contractile unit within each cell of the heart muscle and participates in the regulation of muscle contraction. Exactly how some of mutations in the DNA that produces cMyBP-C lead to severe, early childhood-onset HCM is unclear. The proposed research will examine the impact of an identified HCM-causing mutation in human cells using skin fibroblasts that have been genetically reprogrammed through induced pluripotent stem cells (iPS cells) to become beating heart cells. The HCM mutation within these cells will be expressed and examined in how it affects the way the cells contract, and importantly, how the cells become dysfunctional on their way to developing hypertrophy. For the study, iPS-derived heart cells will be formed into a three-dimensional strip of muscle referred to as human engineered cardiac tissue (hECT). Using this human heart muscle test system, the study will seek to identify how environmental factors may modify, either positively or negatively, the progression of the disease. These studies will enhance our understanding of the genetic forms of HCM and provide insight into the development of more effective treatments.