The major research focus of the Maslen laboratory is on the determining the molecular genetic basis of congenital heart defects. A current interest in the laboratory is the association between the cirrin gene and cardiac malformations known asendocardial cushion defects. The cirrin gene encodes a novel extracellular protein that is expressed in the developing heart. We have determined that deletion of the cirrin gene correlates with the occurrence of endocardial cushion defects in the cytogenetic disorder known as 3p- syndrome. Investigations are now underway to determine if cirrin gene mutations give rise to congenital heart defects of endocardial origin. Additional studies include determining the function of cirrin through the development of a cirrin knockout mouse as a model, and discovering interacting proteins using genetic and biochemical approaches. Identification of the cirrin biochemical pathway will lead to an understanding of the role of cirrin in normal heart development and the pathogenesis of heart malformations.

Another area of interest is the role of the elastin fiber system in the developing heart. Elastic microfibrils are macromolecular structures found in most connective tissues. They make up a multifunctional network that contributes to the elasticity of tissues, but has unknown functions in organ development. Two heritable disorders of elastic microfibrils, Marfan syndrome and congenital contractural arachnodactyly (CCA), provide insight into the structure andfunctions of elastic microfibrils and their different roles in heart development. Individuals with Marfan syndrome have normal heart development, but frequently manifest cardiovascular malfunction later in life. By contrast, about 15% of individuals with CCA are born with cardiac malformations. Comparative studies that reveal the molecular mechanisms behind these closely related disorders will clarify the role of the elastic microfibril system in heart development.

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