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Research interests

A major goal of our research is to understand the complex process of extracellular matrix (ECM) secretion and assembly, with a particular focus on ECM proteins important to the cardiovascular and pulmonary systems. We are interested in how ECM macromolecules assemble into complex polymers in the extracellular space, and how ECM influences the phenotype of cells, including the role of ECM in initiating differentiation and in maintaining appropriate gene expression in the differentiated phenotype. Our research involves identifying biologically active signals within ECM molecules that act directly on cell function. How ECM binds and modulates growth factor signaling is also a focus of our research.

The laboratory also has had a long-standing interest in lung and vascular development and disease. In the cardiovascular system, we are particularly interested in understanding the development of the vessel wall and the recruitment and differentiation of smooth muscle cells. In the lung, we are interested in how ECM proteins influence lung development and susceptibility to diseases, such as emphysema. Using knockout and transgenic mice, we study how the overexpression or underexpression of key ECM proteins influences the development and function of lung and blood vessels. Gene arrays, in situ hybridization, and proteomic approaches are used to characterize tissue alteration associated with each animal phenotype, and physiological studies (lung and vascular compliance, vascular reactivity, blood pressure, etc.) are used to document altered tissue function. We are also interested in human inherited diseases involving proteins of the elastic fiber, including Williams’s syndrome, cutis laxa, supravalvar aortic stenosis (linked to mutations in the elastin gene), Marfan Syndrome (associated with mutations in fibrillin), and pulmonary and systemic hypertension.

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