Professor Simon Satchell
M.B.B.S.(Lond.), Ph.D.(Bristol), M.R.C.P.(RCP), CCST Renal Medicine, CCST General Med
Current positions
Professor of Renal and Vascular Medicine
Bristol Medical School (THS)
Contact
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Research interests
Glomerular endothelial cells (GEnC) form the innermost layer of the glomerular capillary wall which constitutes the glomerular filtration barrier. Normal GEnC possess numerous fenestrations, transcellular pores of 60-80nm in diameter. These fenestrations allow the high hydraulic conductivity of the glomerular filtration barrier, essential for filtration function. The surface of GEnC is, like other endothelial cells, covered by a glycocalyx. This also covers the fenestrations and contributes to the permeability barrier to macromolecules and hence to prevention of passage of albumin and other proteins into the urine.
We are working to understand in detail the contribution of GEnC to the glomerular filtration barrier in terms of the above ultrastructural features and corresponding physiology. We are examining how this normal function is disturbed in disease states and exploring ways of correcting these disturbances therapeutically. We have developed unique conditionally immortalised human GEnC lines to enable detailed studies in vitro.
Specific projects include the role of the glycocalyx and its disturbance by heparanase and by diabetes, regulation and ultrastructure of fenestrations, effects of soluble mediators (VEGF and angiopoietins) on GEnC barrier properties, mechanisms of the anti-proteinuric effect of interferon beta and interactions with podocytes. The later involves development of in vitro models of the glomerular filtration barrier incorporating coculture and flowing medium to induce shear stress.
Projects and supervisions
Research projects
Determining The Therapeutic Potential Of Gene Therapy For Translation Of Glycocalyx Protection Strategies In Chronic Kidney Disease
Principal Investigator
Role
Co-Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
13/02/2024 to 12/02/2025
Project Grant Extension: 'Restoring coronary microvascular endothelial glycocalyx as a potential therapy for diabetic cardiomyopathy'
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
01/06/2016 to 26/09/2019
Aldosterone-enduced endothelial glycocalyx dysfunction, a potential theraputic target in proteinuria? - M Butler fellowship
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
01/08/2015 to 31/07/2018
MRC Via Exeter
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
31/08/2014 to 31/03/2016
BBSRC: International sciencetific interchange scheme
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
05/09/2009 to 05/10/2009
Thesis supervisions
The role of srGAP2 in the regulation of endothelial function
Supervisors
Quantification of the glycocalyx in the study of pre-eclampsia
Supervisors
Therapeutically Targeting Heparan Sulphate To Restore The Endothelial Glycocalyx In Diabetic Microvascular Disease
Supervisors
Aldosterone-induced endothelial glycocalyx dysfunction, a potential therapeutic target in proteinuria?
Supervisors
Identifying matrix metalloproteinases as a therapeutic target to protect the coronary microvascular endothelial glycocalyx in diabetic cardiomyopathy
Supervisors
Using routine healthcare data to investigate the utility of cardiac screening prior to kidney transplantation
Supervisors
Adiponectin in the maintenance and protection of glomerular endothelial cells and the glycocalyx in diabetes
Supervisors
The Glycocalyx and Associated Microvasculature as a Marker of Adverse Pregnancy Outcome in Women with Pre-existing Diabetes Mellitus
Supervisors
Publications
Recent publications
01/06/2024Adiponectin Reduces Glomerular Endothelial Glycocalyx Disruption and Restores Glomerular Barrier Function in a Mouse Model of Type 2 Diabetes
Diabetes
Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes
Cardiovascular Diabetology
Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease
Nature Communications
Aldosterone: Essential for Life but Damaging to the Vascular Endothelium
Biomolecules
Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx
JCI Insight