Professor: Jonathan Butcher
Project Description: Calcific aortic valve disease (CAVD) is the most frequent valvular heart disorder, affecting up to 25% of the elderly population in developed countries. It is characterized by progressive mineralization of the aortic valve leaflets, ultimately obstructing outflow of blood. There are currently no biologically based diagnostic tools or therapeutic strategies. This is due primarily to a lack of fundamental understanding of the homeostatic and pathological interactions between valve cells residing in their 3D matrix microenvironment. Cadherin-11 (Cad-11) is a classical cadherin expressed at the interfaces of mesenchymal tissue that mediates collective cell migration and coordinates acquisition of osteoblastic phenotypes. We recently demonstrated that expression of Cad-11 is exclusively on valve endothelium whereas its re-expression in valve interstitial cells contributes to calcific nodule formation. In this project, we combine molecular biology and tissue engineering technologies to investigate the mechanosensitivity of Cad-11 in the process of calcification in CAVD. Interested students will gain valuable expertise in cell culture models of CAVD (2D, 3D), cyclic stretch bioreactor technology, gene transfection, immunofluorescence imaging, ELISA, IP, western blotting, and/or qPCR.