The Calvin Vary Lab

Research Publications Cell Biology

 

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 Abstract in PubMed). 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 Abstract in PubMed; Koleva et al, 2006 Abstract in PubMed; Mancini et al, 2007 Abstract in PubMed).

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 Abstract in PubMed) in angiogenesis and pathways that contribute to vascular cell differentiation (Tang et al, 2011 Abstract in PubMed; Venkatesh et al, 2011 Abstract in PubMed) 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 Abstract in PubMed, 2008 Abstract in PubMed; Romero et al 2008 Abstract in PubMed; Liu et al 2010 Abstract in PubMed; Romero et al, 2010 Abstract in PubMed), metastasis and the tumor microenvironment (Lakshman, et al 2011 Abstract in PubMed; Romero et al, 2011 Abstract in PubMed). We apply the lessons learned from vascular biology to prostate cancer and vice versa.

Apply to the Sackler School

apply

The priority application deadlines are as follows:

December 1: Basic Science Division PhD Programs

February 15: Building Diversity in Biomedical Sciences

March 31: Post-Baccalaureate Research Program

May 1: Clinical & Translational Science, MS in Pharmacology & Drug Development

June 15: Online Certificate in Fundamentals of Clinical Care Research