Overview
I carried out my PhD at the university of Bristol with Prof Dave Bates (now working at Nottingham University), Prof Steve Harper (Bristol), and Dr Sebastian Oltean (now working at the University of Exeter), studying the alternative splicing of VEGF-A in chronic kidney disease. After finishing my PhD, I developed an interest in the manipulation of VEGF-A splicing in diabetic nephropathy and continued to do a Post-doc with Dr Sebastian Oltean in Bristol. Since July 2017, I have a Research Fellow position at the University of Exeter to continue working with Dr Sebatian Oltean loking at novel alternative splicing events in diabetic nephropathy.
I am working on funding obtained by Dr Sebastian Oltean from the Diabetes UK.
Qualifications
- PhD in Glomerular Physiology and Alternative Splicing (University of Bristol, 2011-2014).
- BSc in Physiology (University of Bristol, 2008-2011).
Research
Research interests
I am interested in alternative splicing in kidney disease, specifically, diabetic nephropathy. Much of our research has been focused on VEGF-A alternative splicing; however, our goals are to determine other proteins that are alternatively spliced in diabetic nephropathy, and to find ways to regulate the way these proteins are spliced as a novel therapeutic avenue.
Research projects
I am currently working on 1 project with Dr Sebastian Oltean: Alternative splicing in diabetic nephropathy.
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Stevens M, Oltean S (In Press). Assessment of Kidney Function in Mouse Models of Glomerular Disease.
J Vis Exp(136).
Abstract:
Assessment of Kidney Function in Mouse Models of Glomerular Disease.
The use of murine models to mimic human kidney disease is becoming increasingly common. Our research is focused on the assessment of glomerular function in diabetic nephropathy and podocyte-specific VEGF-A knock-out mice; therefore, this protocol describes the full kidney work-up used in our lab to assess these mouse models of glomerular disease, enabling a vast amount of information regarding kidney and glomerular function to be obtained from a single mouse. In comparison to alternative methods presented in the literature to assess glomerular function, the use of the method outlined in this paper enables the glomerular phenotype to be fully evaluated from multiple aspects. By using this method, the researcher can determine the kidney phenotype of the model and assess the mechanism as to why the phenotype develops. This vital information on the mechanism of disease is required when examining potential therapeutic avenues in these models. The methods allow for detailed functional assessment of the glomerular filtration barrier through measurement of the urinary albumin creatinine ratio and individual glomerular water permeability, as well as both structural and ultra-structural examination using the Periodic Acid Schiff stain and electron microscopy. Furthermore, analysis of the genes dysregulated at the mRNA and protein level enables mechanistic analysis of glomerular function. This protocol outlines the generic but adaptable methods that can be applied to all mouse models of glomerular disease.
Abstract.
Author URL.
Full text.
Stevens M, Oltean S (2018). Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease.
Genes (Basel),
9(2).
Abstract:
Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease.
Vascular endothelial growth factor a (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3' splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys-Drash syndrome. Using mouse models of kidney disease where the VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A165b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor kinases involved in the regulation of VEGF-A terminal exon splicing has provided some mechanistic insight into how VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs.
Abstract.
Author URL.
Full text.
Publications by year
In Press
Stevens M, Oltean S (In Press). Assessment of Kidney Function in Mouse Models of Glomerular Disease.
J Vis Exp(136).
Abstract:
Assessment of Kidney Function in Mouse Models of Glomerular Disease.
The use of murine models to mimic human kidney disease is becoming increasingly common. Our research is focused on the assessment of glomerular function in diabetic nephropathy and podocyte-specific VEGF-A knock-out mice; therefore, this protocol describes the full kidney work-up used in our lab to assess these mouse models of glomerular disease, enabling a vast amount of information regarding kidney and glomerular function to be obtained from a single mouse. In comparison to alternative methods presented in the literature to assess glomerular function, the use of the method outlined in this paper enables the glomerular phenotype to be fully evaluated from multiple aspects. By using this method, the researcher can determine the kidney phenotype of the model and assess the mechanism as to why the phenotype develops. This vital information on the mechanism of disease is required when examining potential therapeutic avenues in these models. The methods allow for detailed functional assessment of the glomerular filtration barrier through measurement of the urinary albumin creatinine ratio and individual glomerular water permeability, as well as both structural and ultra-structural examination using the Periodic Acid Schiff stain and electron microscopy. Furthermore, analysis of the genes dysregulated at the mRNA and protein level enables mechanistic analysis of glomerular function. This protocol outlines the generic but adaptable methods that can be applied to all mouse models of glomerular disease.
Abstract.
Author URL.
Full text.
2018
Stevens M, Oltean S (2018). Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease.
Genes (Basel),
9(2).
Abstract:
Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease.
Vascular endothelial growth factor a (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3' splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys-Drash syndrome. Using mouse models of kidney disease where the VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A165b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor kinases involved in the regulation of VEGF-A terminal exon splicing has provided some mechanistic insight into how VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs.
Abstract.
Author URL.
Full text.
Megan_Stevens Details from cache as at 2019-02-16 04:50:14
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External Engagement and Impact
Editorial responsibilities
- I am on the editorial board for the International Journal of Renal Diseases and Therapy.
Invited lectures
- The International Splicing Conference 2016, Lisbon.
- The international Splicing Conference 2018, Lisbon (confirmed invited speaker).
Supervision / Group
Postgraduate researchers
- Monica Lamici Ayine PhD Student