Vascular biology research forms a major part of the Bristol Renal interest and expertise from the study of glomerular endothelial cells in vitro and in vivo to the role of glycocalyx or the importance VEGF gene products and splice isoforms both in physiology and disease. We employ a range of techniques, cell lines and experimental approaches.
In vitro glomerular endothelial cells biology
Dr Simon Satchell's group is the first in the world to have developed conditionally immortalized glomerular endothelial cells. This provide an invaluable tool in understanding the cellular and molecular biology of these cells, especially in the context of their tissue-specific functions in the glomerulus and differences with endothelial cells from other vascular beds.
Methods to study endothelial glycocalyx
The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins that cover the surface of endothelial cells. Its importance in physiology and pathology is under intense investigation. Drs Satchell and Foster have developed a range of techniques to separate various glycocalyx components and understand their role while Dr Chris Neal is an expert in electron microscopy imaging of the glycocalyx.
Measurement of glomerular water permeability
The way water and solutes cross the glomerular basement membrane physiologically and how this is perturbed in various kidney diseases is an area of intense research. Drs Satchell, Foster and Oltean are using methods initially developed by Dr Andy Salmon to measure single glomerular permeability by using confocal microscopy or permeability rigs.
Vascular Endothelial Growth Factors in the kidney
VEGF has emerged in recent years as an important molecule both in the physiology as well as various pathologies of the kidney, its expression being directly correlated with chronic kidney diseases and GFR. There is various expertise within our group, with Dr Becky Foster interested in studying both VEGF-A and VEGF-C in vitro and in vivo in transgenic models and Dr Seb Oltean’s group interested in studying regulation of VEGF-A splice isoforms, as well as other splice variants in the VEGF signaling axis. Dr Oltean uses a novel technology – splicing-sensitive fluorescent reporters to understand how splice isoforms may be manipulated for therapeutic purposes as well as a range of transgenic mice in which expression of VEGF splice isoforms can be induced in the kidney.