Nuclear receptors: PPARs, FXR, RXR, PXR and beyond
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Nuclear receptors are ligand activated transcription factors that control a variety of important developmental, metabolic, nutritional, immune and xenoensing roles.
In man there are 48 nuclear receptors. We still no very little about a huge number of these receptors. We are interested in the expression, regulation, roles and the type of mediators and drugs that may activate nuclear receptors. |
PPARs
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Peroxisome proliferator-activated receptors (PPARs) are a family of 3 nuclear receptors with important roles in fatty acid signalling. We found all PPARs expressed in endothelial cells and our current research has focussed predominantly on PPARb/d.
We found PPARb/d activation induces angiogenesis and inhibits inflammation. We are examining examining the pathways by which PPARb/d causes these effects and are examining new roles for PPARb/d in vascular biology and non-vascular tissue. |
FXR
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The farnesoid X receptor (FXR) is a bile acid nuclear receptor which can also be activated by polyunsaturated fatty acids.
We found FXR is expressed in vascular tissue as well a number of cancers including breast cancer. Activation of FXR is inhibitory in vascular inflammation and drugs that activate it are novel potential therapies for cardiovascular disease. We are currently looking at the roles of FXR in vascular and cancer biology. |
PXR
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The pregnane X receptor (PXR) is a receptor that senses a variety of chemicals and drugs to induce pathways of detoxification.
We found PXR was present in vascular cells and when activated, induced similar pathways of detoxification. We are now looking at the roles of PXR in vascular biology. We are also examining the role of the vasculature as an organ for detoxification. |
nuclear receptor network
We now know vascular and inflammatory cells express a wide variety of nuclear receptors. For many of these nuclear receptors we still don't know much about their regulation, co-regulators, activators and roles in vascular inflammation. We are currently looking to fill some of these gaps in our knowledge.