Understanding on the roles of receptor signaling in cardiovascular development and disease.
Regulation of Blood Vessel Formation and the Etiology of HHT
Blood vessel formation is a multi-step process. Endoglin is a TGFβ/ bone morphogenetic protein (BMP) coreceptor for the TGFβ/BMP receptor, ALK1, both of which are required for angiogenesis. In humans, haploinsufficiency of endoglin or ALK1 results in Hereditary Hemorrhagic Telangiectasia (HHT), a vascular disease characterized by a loss of arteriovenous identity and aberrant vSMC incorporation in fragile vessels.
Our research is focused on the roles of TGFβ/BMP signaling via endoglin and ALK1 in cardiovascular development and disease. Our work takes advantage of our state-of-the-art mass spectrometry core facility. Recent discoveries include BMP9-directed changes in endothelial cell protein chemokine signatures, including the regulation of SDF1 and MCP1 by BMP9 (Young et al., Blood, 2012) and BMP9 signaling crosstalk with the Hippo pathway, a regulator of endothelial cell mechanotransduction (Young et al., PLOS ONE 2015).
More recent interests include: 1) the interaction of the BMP and Notch signaling pathways in endothelial cell signaling, 2) the requirement for endoglin in embryonic vascular patterning carried out by Pax3-positive vascular cell progenitor cells (See Figure, “Targeted deletion of endoglin in Pax3-positive cells; e9.5 mouse embryonic intersomitic vessels), and 3) the role of BMP9 in the regulation of lipid metabolism.