Junctional Complexes in the human Placenta (Wellcome Trust)
The diabetic human placenta (Wellcome Trust)
In vitro model of the outer retinal barrier (Wellcome Trust)
Mathematical modelling of placental flow (MRC; EU)
Angiogenesis and junctional adhesion molecules (AICR)
Molecular mechanisms behind endothelial dysfunction (Anatomical Society)
Endothelial barrier function, junctional adhesion molecules, human placenta, angiogenesis, diabetes mellitus.
Physiological and pathological angiogenesis, adhesion molecules and signalling.
We research into how blood vessels grow (angiogenesis) and maintain a selective barrier (permeability) in health and how it may go wrong in disease. These functions are extremely important in the human placenta, which protects and feeds the growing baby throughout pregnancy. Thus our main study is that into understanding blood vessel function in the human placenta in normal pregnancies and those complicated by diabetes and pre-eclampsia. To aid these studies we have endothelial cell models in culture (2-D and 3-D) which lets us look at the role of individual key growth factors and into how we may control or revert pathological processes. Our second interest is into diseases of the eye which includes diabetes and age-related macula degeneration. We have a successful human model which mimics the arrangements of the blood vessels in the eye. Again, increased angiogenesis and leakiness can lead to blindness and we are investigating ways to prevent this.
Impairment in vascular function, specifically increased angiogenesis and vascular leakage, is a major complication of diseases such as diabetes, cancer and hypertension. The adhesion molecules which hold the lining cells i.e. the endothelial cells together play a role in both these functions. Our group uses ex vivo human perfusion models and in vitro cell cultures to understand the signalling and regulation of these molecules and how they may go wrong, specially in diabetes. Our major interest is the functioning of blood vessels in the human placenta, in normal and diabetic pregnancies. The placenta is vital for fetal nutrition, development, growth and well-being throughout gestation and impaired placental function causes fetal morbidity and mortality. Moreover, in-utero disturbances may lead to fetal programming and increased risk of cardiovascular diseases and diabetes in adulthood. We wish to develop therapeutic strategies to prevent the vascular complications we have shown to exist in the placenta in pregnancies complicated by diabetes. We have a near-physiological, extra-corporeal placental perfusion system which allows us to look at the effect of key factors on trans-placental transport, whilst in vitro models allow more long term effects on angiogenic parameters to be studied. The placental perfusion system allows monitoring of maternal and fetal blood flow and pressure and lends itself to studies of directional transport. We have expertise into growth of primary endothelial cells in 2-D or 3-D culture systems to study barrier properties and angiogenesis. We have a trilayer model of the outer retinal barrier which allows studies into drug transport as well as hypoxia-mediated neo-vascularisation. Immunocytochemistry, confocal microscopy and real time imaging, as well as standard molecular biology which include immunoblotting are routinely used in our laboratory. We also have expertise of immuno-electron methods and standard transmission electron microscopy. The growth factors of specific interest to us include vascular endothelial growth factor and angiopoietin-1. We have knowledge of the behaviour of junctional adhesion molecules (occludin, VE-cadherin and beta-catenin) in regulating paracellular permeability, endothelial survival and angiogenesis.
We are interested in the potential use of human mesenchymal stem cells from the umbilical cord in vascular repair. Research is on going using real time imaging and other laboratory cell biology techniques.