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"Experimental Frameworks for Analysis of Heart Valve Mechanobiology"
Jane Grande-Allen, PhD
Associate Professor of Bioengineering
Heart valve disease has devastating consequences for the health and survival of its victims. Valve disease is widely prevalent in our society, with valve replacement or repair in almost 100,000 people in the United States and 275,000 people worldwide each year. Myxomatous, or “floppy” disease of the mitral valve alone affects up to 5% of the population, and calcific aortic valve disease is a major problem associated with aging, obesity, diabetes, and smoking. The treatment of these conditions represents substantial health care costs. Despite these statistics, the basic biology of heart valves is sparsely studied and barely understood and there are no cures for valve disease other than expensive surgical repairs or replacements, nor any medications specific for valve disease. The focus of my research group is to comprehensively characterize and perturb the valvular tissue and cell phenotypes in normal and diseased heart valves, as the first major step in finding the causes of heart valve diseases, in identifying the early stages and patients at risk, in developing drugs for its treatment, and for ultimately reducing the incidence of the disease in the population. Our research has helped to define the nascent field of valve mechanobiology and furthermore developed tools such as bioreactors to make these research studies possible. These investigations have covered the distribution and regulation of extracellular matrix within the valve and how these are governed by the mechanical loads experienced by the cells within native valves, engineered valve tissues, or cells grown in 2D cultures. More recently, we have begun to develop platforms to investigate the mechanobiology of valvular endothelial cells and the associated regulation of hemostatic behavior.