DrGraeme Birdsey

Overview
My work focuses on the role of the Ets-related gene ERG in regulating endothelial gene expression and angiogenesis.

Sprouting Angiogenesis
Angiogenesis is the growth of new blood vessels and is an important natural process that occurs during wound healing and development. However, abnormal blood vessel growth underlies many diseases, including cancer, age-related blindness, diabetic ulcers, stroke and cardiovascular disease.

Angiogenesis involves the sprouting of endothelial cells from existing blood vessels in a tightly regulated process that requires the integration of signals from growth factors, adhesion molecules and other cellular pathways.

Specialised endothelial tip cells, which are highly motile and extend numerous filopodia, lead the outgrowth of the vessel sprout towards gradients of VEGF.


Transcriptional Regulation of Angiogenesis
Angiogenesis depends on the dynamic regulation of endothelial cell gene expression. There is a complex network of transcriptional regulators that have a fundamental role in regulating the precise temporal and spatial co-ordination of the expression of multiple genes during angiogenesis.

My interest in angiogenesis focuses on the role of the Ets-related gene ERG (a member of the ETS family of transcription factors). Erg is one of the most highly expressed ETS transcription factors in endothelial cells and drives the expression of genes that define the endothelial lineage, including many that are involved in angiogenesis.

We have shown that Erg is required for endothelial monolayer stability, endothelial cell survival and angiogenesis - partly through driving expression of the adhesion molecule VE-cadherin. Birdsey et al (2008) Blood 111(7): 3498-506
To understand in more detail the molecular mechanisms regulating angiogenesis, we make use of a number of techniques including:

transcriptional biochemistry
microarray analysis
computational biology
confocal immunofluorescence microscopy
time-lapse microscopy
in vitro and in vivo models of angiogenesis (e.g postnatal retinal sprouting, co-culture and Matrigel tube formation assays).