Research

Work in our laboratory uses the engineering analysis of tissue composition and behavior to investigate tissue and cellular responses to disease, using the cardiac valves as a paradigm for other soft tissues. These projects are interdisciplinary, innovative, medically and biologically applicable, and clinically relevant. Heart valve disease, whether presenting as a primary dysfunction requiring surgical repair or replacement, or as a secondary complication to another disease such as heart failure, affects the health of hundreds of thousands of Americans (and patients worldwide) every year.

The overall focus of our research is to characterize and eventually to manipulate the structure-function-environment relationship of cardiac valves in an integrative fashion (cellular, tissue, organ, and clinical). The matrix composition and material properties of heart valves are believed to be determined by the load patterns imposed during valve function. Consequently, alterations to the normal tissue loading patterns will affect the cellular phenotypic production of extracellular matrix and transform the valve morphology, mechanics, and function. To relate tissue composition and mechanics in leaflets and chordae from normal and diseased mitral valves, our laboratory performs mechanical testing, biochemical measurements, and microstructural analysis of the extracellular matrix (especially glycosaminoglycans (GAGs) and proteoglycans) of these tissues. We then correlate these data with echocardiographically assessed cardiac functional parameters and clinical demographics. We are also using cells, organ cultures, and tissue engineering approaches to investigate valve disease from a more mechanistic angle. The main diseases that we study are myxomatous ("floppy") mitral valve disease and secondary remodeling of the heart valves in patients with heart failure, but this research may have implications and applications for other soft tissues. Our goal in characterizing the normal and pathological mechanisms of valvular remodeling is to derive novel surgical and medical therapies that can be used to treat patients earlier in the disease process.

Our research is centered around the following aims:

(1) Understanding the extracellular matrix basis for the tissue mechanics of valves and other soft tissues, particularly with respect to proteoglycans.

(2) Identification, characterization, and mechanical/humoral/pharmaceutical control of valvular glycosaminoglycans and proteoglycans.

(3) Biochemical, proteomic, biomechanical, and echocardiographic quantification of valvular remodeling in clinical congestive heart failure (a secondary valve disease) and myxomatous mitral valves (a primary valve disease).

(4) Development of in vitro surrogates (via cell / organ culture and tissue engineering) and bioreactor systems to study disease and remodeling in valves and other soft tissues.

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Research