A research team led by Arnold W. Strauss, M.D., professor of pediatrics and of molecular biology and pharmacology, has received a five-year $8.7 million Specialized Center for Research (SCOR) grant. The SCOR grant, from the National Heart, Lung, and Blood Institute, will fund six studies at three institutions on the genetic basis of heart disease in children.
"The main idea behind this grant is to find genes that cause heart disease in children," said Strauss, who also is director of the Division of Pediatric Cardiology. "It's a relatively new concept that congenital heart disease, such as holes in the heart and other defects, are due to defective genes."
In the first project, Zhi-Fang Zhang, M.D., research assistant professor of pediatrics, and Charles E. Canter, M.D., associate professor of pediatrics, will work with Strauss to explore the genetic causes of pediatric cardiomyopathy or heart muscle disease in children, a common cause of death. As well as identifying the responsible genes, they will analyze the mechanisms of abnormal function of the heart in animal models. In this project, they hope to gain a better understanding of the proteins essential for normal cardiac function.
In a second project, Daniel P. Kelly, M.D., associate professor of medicine and of molecular biology and pharmacology, and Jean E. Schaffer, M.D., assistant professor of medicine and of molecular biology and pharmacology, will study defects in myocardial fatty acid import and use, an important cause of the inherited cardiomyopathy that can cause sudden death in children and young adults. They already have established and characterized genetically engineered mouse lines with altered expression of proteins involved in myocardial fatty acid import and use. They will use these mice to test the hypothesis that accumulation of intracellular lipid plays an early role in heart failure and sudden death. The results should provide significant insight into the role of disturbances in myocardial lipid metabolism and the pathogenesis of inherited and acquired forms of heart failure.
David B. Wilson, M.D., Ph.D., associate professor of pediatrics and of molecular biology and pharmacology, will lead a project to study GATA-4, an important factor in heart development. Wilson; Anne V. Hing, M.D., assistant professor of pediatrics; and Michael S. Watson, Ph.D., associate professor of pediatrics and of genetics, will try to determine how this molecule contributes to congenital heart disease. These results will provide further evidence that a single defective gene can produce different anatomical abnormalities in the heart.
In the fourth project, Robert P. Mecham, Ph.D., professor of cell biology and physiology and of medicine, will focus on elastin, the major connective tissue protein of elastic structures such as large blood vessels. Several human diseases have been linked to mutations in elastin. Mecham and colleagues will determine how these mutations alter the functional properties of elastin, leading ultimately to blood vessel abnormalities.
The fifth and sixth projects will take place in Utah and South Carolina. In the fifth project, H. Joseph Yost, Ph.D., associate professor of oncological sciences at the University of Utah, hopes to advance the understanding of genetic and environmental disturbances that result in congenital heart malformations in children.
D. Woodrow Benson, M.D., Ph.D., professor of pediatrics and cell biology and anatomy at the Medical University of South Carolina, is leading the sixth project, which will explore the genetic basis of congenital heart disease.
Strauss also recently received a $1 million grant from the National Heart, Lung, and Blood Institute to train fellows in developmental cardiology and pulmonary medicine.
