Defining New Mechanisms to Uncover the Early Developmental Manifestations of Arrhythmogenic Cardiomyopathy in Children (2012-2013)
Farah Sheikh, PhD
Assistant Professor Department of Medicine (Cardiology)
The Regents of the University of California
University of California at San Diego
Arrhythmogenic Cardiomyopathy (AC) is an especially devastating inherited heart muscle disease that traditionally affects the right side of the heart and leads to sudden cardiac death in young children and people. Early detection is hindered because children and people carrying mistakes in the genetic code linked to AC have highly variable clinical symptoms, making AC and catastrophic cardiac events very hard to predict and avoid. Evidence suggests that 40% of cases are caused by mistakes in genes that are essential for holding the mechanical integrity of heart muscle cells together or cell junctions (desmosomes); however, what is missing is a fundamental understanding of the early developmental cues that drive the right heart to be more susceptible to disease in children.
The proposed research combines state-of-the-art genomic, human cardiac stem cell and genetic mouse engineering approaches to characterize the biological actions of a novel group of short non-coding RNAs that we believe may act as master regulators of right heart health and the disease, AC. We believe information gained from our proposal funded by Saving tiny Hearts Society will lead us to uncover novel causes and mechanisms underlying the early developmental manifestation of AC in children that will also bring to light a new entry point to study and intervene with the underlying developmental causes of AC, which is playing an increasingly prevalent role in pediatric populations.