Kidneys​

Our kidneys are responsible for excreting waste products as well as contributing to the control of blood pressure, the maintenance of healthy bones and to the production of red blood cells. Each kidney has about a million tiny kidney filters, known as glomeruli, which allow water and small molecules to pass freely but prevent cells and large molecules from leaving the blood circulation. The persistent loss of protein molecules from the blood into the urine is an early sign of kidney disease and for many individuals there is a relentless progression to kidney failure. The worldwide incidence of kidney disease is increasing, and we need to understand the underlying mechanisms of disease to improve early detection and targeted therapies.

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Our research

Research in the Lennon Lab  is focused on understanding mechanisms of glomerular disease, the leading cause of kidney disease in adults and children. The glomerular capillary wall is a highly sophisticated filtration barrier that comprises specialised endothelial cells, the glomerular basement membrane and specialised epithelial cells known as podocytes (Figure 1). Basement membrane regulation is fundamentally required for barrier integrity and we have developed proteomic methods to resolve the cell adhesion-matrix interface and have interrogated ultrastructure using serial block-face scanning electron microscopy. Using a combination of in vitro systems (glomerular cell coculture, kidney organoids) and animal models (mouse, zebrafish) we now seek to understand mechanisms of glomerular barrier injury and repair.

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Basement membranes

Glomerular function requires regulation between cells and extracellular matrix and our research has a focus on glomerular matrix and in particular basement membrane biology. The molecular composition of glomerular matrix has been traditionally investigated by candidate-based approaches, which have led to the identification of core basement membrane components including laminins, type IV collagen, nidogens and heparan sulphate proteoglycans. We have used unbiased approaches to investigate matrix and we used mass spectrometry-based proteomics to investigate the human glomerular matrix. We found a complex network of 144 structural and regulatory matrix proteins in the normal glomerulus and in addition we identified compositional change associated with glomerular dysfunction.