Skip to main content
Graduate School of Biomedical Sciences

The Calvin Vary Lab

Regulation of Blood Vessel Formation

Blood vessel formation is a multi-step process. Endoglin is a TGFβ coreceptor required for angiogenesis. Endoglin null embryos exhibit a loss of arteriovenous identity and defective vascular smooth muscle cell (vSMC) recruitment. Haploinsufficiency of endoglin results in Hereditary Hemorrhagic Telangiectasia (HHT), characterized by a loss of arteriovenous identity and aberrant vSMC incorporation in fragile vessels.

My laboratory made the initial discoveries that: 1) endoglin has regulatory functions in cytoskeletal-localized adhesion proteins, 2) endoglin is expressed in smooth muscle cells in human atherosclerotic lesions, and 3) endoglin directly interacts with ALK1 and is a substrate for ALK1 phosphorylation, leading to Smad-independent signaling in vascular cells (Bernabeu et al, 2007). These discoveries have changed our understanding of the roles of endoglin in vascular cells and its implications in human cardiovascular disease (Conley et al, 2004; Koleva et al, 2006; Mancini et al, 2007).

Blood vessel formation is a multi-step process. Endoglin is a TGFβ coreceptor required for angiogenesis. Endoglin null embryos exhibit a loss of arteriovenous identity and defective vascular smooth muscle cell (vSMC) recruitment. Haploinsufficiency of endoglin results in Hereditary Hemorrhagic Telangiectasia (HHT), characterized by a loss of arteriovenous identity and aberrant vSMC incorporation in fragile vessels.

In recent work we explored a cell autonomous role for endoglin in endothelial and vSMC recruitment and arteriovenous specification via COUPTFII (Mancini et al, 2009) in angiogenesis and pathways that contribute to vascular cell differentiation (Tang et al, 2011; Venkatesh et al, 2011) and HHT. We propose to obtain human HHT specimens to extend the observations to human tissues.

We are also interested in the role of endoglin in prostate cancer progression (Craft et al, 2007, 2008; Romero et al 2008; Liu et al 2010 Romero et al, 2010), metastasis and the tumor microenvironment (Lakshman, et al 2011; Romero et al, 2011). We apply the lessons learned from vascular biology to prostate cancer and vice versa.