Title: A DDR1-Collagen Story in Vascular Biology

Speaker: Prof. Gunjan Agarwal, Ohio State University

Abstract: Collagen type 1 is the most abundant extracellular matrix protein in adult tissues. The interaction of cells with collagen occurs via specific receptors. We describe here a two-way cross-talk between collagen and the collagen receptor discoidin domain receptor (DDR1). DDR1 is a receptor tyrosine kinases expressed in a variety of mammalian cells. On one hand DDR1 regulates the collagen fibril structure while on the other hand the fibrillar state of collagen impacts receptor function. An altered collagen fibril structure in turn can affect cell-matrix interactions, which have multiple manifestations in health and disease. We elucidate such an effect in vascular biology, wherein the DDR1 knockout mice exhibited enhanced platelet-collagen adhesion and increased thrombogeneity of the vessel wall. Our investigations also reveal that structural alterations in collagen fibril (accompanied by DDR1 activation) exist in vascular diseases such as aortic aneurysms, which can impact platelet adhesion, vascular calcification and mechanics.