The overall goal of our laboratory is to understand the role of bone morphogenetic proteins (BMPs), and their inhibitors and receptors in vascular disease such as atherosclerosis, vascular calcification, diabetic vascular disease and arteriovenous malformations (AVMs). We have identified a regulatory pathway, in which BMP-2/4 induces the expression of activin-like kinase receptor 1 (ALK1), a receptor for BMP-9. ALK1 is essential for angiogenesis and regulates expression of vascular endothelial growth factor (VEGF) and BMP-inhibitors including matrix Gla protein (MGP). We have found that this regulatory pathway is affected in vascular disease and appears to be essential for vascular homeostasis. We have also established a source of cardiovascular precursor cells for use in our studies, so-called de-differentiated fat (DFAT) cells, derived from white mature adipocytes. Our current projects focus on (1) how MGP prevents vascular calcification, (2) the role of BMP-signaling in diabetic vascular disease, (3) the mechanism of AVMs, (4) how DFAT cells differentiate into cardiovascular cells, and (5) biological patterns involving BMP and MGP.

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