Endothelial Homeostasis and Angiogenesis

The main focus of the group is endothelial homeostasis and angiogenesis in cardiovascular (CV) disease.

Endothelial cells (EC) regulate critical vascular functions, such as the traffic of cells from blood to tissues, the formation of blood clots, permeability and vascular tone. Maintenance of endothelial homeostasis is essential for the prevention and control of many diseases, including atherosclerosis. A number of stimuli (high LDL-cholesterol, smoking, high blood pressure, viruses) cause loss of the homeostatic balance and chronic activation of pro-inflammatory pathways. Many pathways regulate these processes. We are interested in understanding how EC maintain homeostasis through the regulation of gene expression. In particular we are studying the role of ETS transcription factors and of the ETS related gene Erg. Using in vitro and in vivo models, we investigate the role of Erg in endothelial homeostasis, inflammation and angiogenesis. We aim to demonstrate that Erg is a master regulator of endothelial homeostasis, and therefore may represent a promising novel therapeutic target for the prevention of CV disease.

We are also interested in translating our endothelial research in patients; for this reason we have developed a translational approach, by isolating Endothelial Progenitor Cells (EPCs) from blood. EPC are bone marrow-derived stem cells that have the ability to differentiate into mature endothelial cells, thus contributing to postnatal vasculogenesis and endothelial repair at sites of endothelial cell damage. The potential for EPCs as biomarkers of vascular injury and also as therapeutic tools in man is currently being explored in several ways.

Confocal immunofluorescence microscopy of human umbilical vein endothelial cells showing expression of Erg in the nucleus (green) and one of its targets – the adhesion molecule VE-cadherin along the cell junctions (red).

Immunofluorescence image of endothelial cells showing the microtubule cytoskeleton (green) and nuclei (purple).

Selected Publications

Birdsey GM; Dryden NH; Amsellem V; Gebhardt F; Sahnan K; Haskard DO; Dejana E; Mason JC; et al. (1 Apr 2008). Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood. 111:3498-3506.

Randi AM; Sperone A; Dryden NH; Birdsey GM. (Dec 2009). Regulation of angiogenesis by ETS transcription factors. BIOCHEM SOC T. 37:1248-1253.

Huang MT; Mason JC; Birdsey GM; Amsellem V; Gerwin N; Haskard DO; Ridley AJ; Randi AM. (1 Sep 2005). Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis. Blood. 106:1636-1643.