Our lab focuses on the examination and manipulation of the molecular regulatory mechanisms of heart development and disease. We use experimental embryological, genetic and molecular approaches to conduct mechanistic analyses of the development of myocardial and connective tissue cell lineages in the heart.
Using chick, mouse, pig and human systems, we work to identify critical regulatory interactions in the developing and diseased heart and to manipulate these interactions in vivo. We have developed in vitro culture systems in which we examine the molecular regulatory events that control cardiac lineage determination, valve cell maturation, valve calcification, and myocardial homeostasis. The goal of our work is to establish relationships between signaling pathways and transcription factors that control the cardiac development and contribute to cardiovascular disease.
Our work over the past few years has established striking parallels in the regulatory hierarchies that control heart valve development and those that control the development of other connective tissue cell types including cartilage, tendon and bone. Many of these regulatory interactions also are active in calcific and myxomatous heart valve disease. Likewise, regulatory interactions that control cardiac fibroblast and smooth muscle differentiation in epicardial cells during development are reactivated in cardiac fibrotic disease.
We have demonstrated that pediatric and even adult valve diseases are characterized by reactivation of developmental gene regulatory programs. A goal of our research is to elucidate mechanisms of valve disease by combining studies investigating the regulatory pathways controlling normal valve development in animal models with analysis of the molecular progression of disease in pediatric and adult human tissue specimens. Ultimately, this work promises to identify new therapeutic targets to treat heart valve disease and improve child health.