Past members of the group
Christine Chew 2015-2020 (Versus Arthritis Clinical training research fellow)
Sam Rhoden 2014-2020 (PhD student and PDRA)
Will Loewenhardt 2016-2019 (PhD student)
Joseph Luckman 2019 (Intercalating Masters of Research)
Alexander Hale 2018 (Master rotation project)
Keira Bralsford 2018 (UG final year project)
Francesco De Luca 2017 (Visiting Masters student from Lund)
Saule Gasiunas 2017 (APEP project)
Abby Huckle 2016-2017 (Intercalating Masters of Research)
Salman Hosawi: 2013-2018 (Masters and PhD student)
Michael Randles 2011-2017 (PhD student and PDRA)
Stephanie Murphy 2010-2016 (Research Technician)
Sophie Collinson 2014-15 (Intercalating Masters of Research)
James McCaffrey 2011-2015(MRC Clinical training research fellow)
Hitesh Khanna 2013-14 (Intercalating Masters of Research)
Christine Chew 2014 (Academic Clinical Fellow)
Hellyeh Hamidi 2011-2013 (Post-doctoral Research Assistant)
Emma Kennard 2013 (Undergraduate medical student project option)
Thomas Denny 2011-2012 (MPhil)
Rebecca Kirkwood Wilson 2012 (Undergraduate medical student project option)
Jessica Ball 2011-12 (Intercalating Pathology BSc- Wolfson award)
Greg Lee 2010 (Undergraduate medical student project option)
James Peters 2010 (Undergraduate medical student project option)
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.
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.
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.
Figure 1 The glomerular filtration barrier comprises endothelial cells, glomerular basement membrane (GBM) and podocytes. In the early stages of glomerular dysfunction, we have observed GBM expansion and splitting, preceding podocyte foot process effacement and the appearance of podocyte protrusions in the GBM. In progressive disease there are further changes in cell and matrix morphologies.
We have collective expertise in a range of laboratory techniques and we use these to study human cells (podocytes, glomerular endothelial cells and mesangial cells) and kidney organoids in addition to zebrafish, mouse and human tissue to investigate glomerular cell biology in health and disease.
Western blotting, immunoprecipitation, immunocytochemistry, immunohistochemistry, molecular cloning, PCR,
in-situ hybridisation, transfections, generation of recombinant proteins, siRNA-mediated knockdown.
Specialised techniques and assays
Isolation of human and mouse glomeruli
Isolation of glomerular extracellular matrix
Isolation of adhesion complexes from cells in culture
Mass spectrometry-based proteomics and bioinformatic analyses
3D electron microscopy
Biomolecular analysis including surface plasmon resonance
ECIS: Electric Cell-substrate Impedance Sensing
Cell sheet engineering and 3D cell culture systems
Year Old Lab
Wellcome Centre for Cell-Matrix Research,
Michael Smith Building,
University of Manchester,
Website Design: Alina Wolowczyk and Marcel Stanek