Regulation of the endothelial cell barrier integrity is critical in inducing new blood vessel formation (angiogenesis), in developing an inflammatory response and importantly in resolving or inhibiting the response. We have shown that microRNAs are essential in these events and moreover are altered when there is chronic unresolved disease. Our investigations are into determining the important molecular targets of the microRNAs, understanding the dysregulation of these microRNAs in disease where endothelial cell angiogenesis and permeability are major contributing factors and developing these microRNAs or their inhibitors as potential therapeutics.
Technologies include, molecular studies of target expression, genetic manipulation of the microRNAs, in vitro models of endothelial cell function, state-of-the art imaging, animal models of disease and zebrafish models for vascular development.
ere you can add any other information that you wish to about yourself and your research. Our work in the area of microRNAs and endothelial cell function has:
1. Identified a miRNA that targets the endothelial cell specific adhesion molecule VE cadherin. This protein is a major regulator of angiogenesis and endothelial cell integrity.
2. Developed a novel antagonist (antagomir or Blockmir) that is functional in animal models of disease where angiogenesis and vascular oedema are contributing factors to recovery (Young et al Blood 2013). Our work now is to further the studies into this antagonist as a potential therapeutic by defining its effects in diseases such as cancer, stroke and heart disease.
3. We have also defined a further set of microRNAs that may act in concert to regulate other aspects of angiogenesis and vascular oedema. Thus, we aim to develop an understanding of the co-ordinated regulation of microRNAs and their specific targets in controlling endothelial cell integrity.
Additional supervisor: Mathew Vadas
The opportunity ID for this research opportunity is 1428