University of Exeter Medical School

Megan Stevens

Megan Stevens

Postdoctoral Researcher

 ms866@exeter.ac.uk

 Living Systems Institute 

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

Megan has a background in physiology and cellular biology. Her research career has mostly focused on the role of alternative splicing in kidney disease, specifically diabetic nephropathy. More recently, she has been focusing on the identification of novel drug targets in cancer. Megan currently works as a Postdoctural Researcher in Dr Benjamin Housden's at the LSI, University of Exeter. Her current research interests are focused on identifying novel drug targets for Neurofirbomatosis type 1 (NF1) using combinatorial screening in a Drosophila NF1 mutant model.

Megan is also currently co-supervisor to two PhD students within Dr Sebastian Oltean's lab, and two MSc students with Dr Housden.

Qualifications

  • PhD in Glomerular Physiology and Alternative Splicing (University of Bristol, 2011-2014).
  • BSc in Physiology (University of Bristol, 2008-2011).

Career

Megan carried out a BSc degree in Physiology at the University of Bristol (2008-2011), followed by a PhD in Physiology under the supervision of Professor David Bates (currently Nottingham University), Professor Steven Harper (Bristol University) and Dr Sebastian Oltean (currently Exeter University) at the University of Bristol (2011-2014). Her PhD thesis was titled: "Manipulation of VEGF-A splicing repertoire as a potential therapeutic in chronic kidney disease".

In 2015, Megan was awarded a 1-year Junior Fellowship from the Richard Bright VEG Research Trust to continue her research in to the role of VEGF-A splicing in chronic kidney disease, with a focus on diabetic nephropathy. This project was supervised by Dr Oltean at the University of Bristol. From here. Megan continued to work with Dr Oltean as a post-doctoral researcher on BHF and Richard bright VEGF Research Trust funded projects on how VEGF-A splicing can be manipulated to be therapeutically beneficial in diabetic nephropathy.

In 2017, Megan moved to the University of Exeter to work as a Research Fellow, under the supervision of Dr Oltean. At this point, Megan began to establish herself as an independent researcher in her niche area of research: the role of alternative splicing on the development and progression of diabetic nephropathy. She is curently working on a Diabetes UK funded project grant developing pilot data on the role of the apoptosis gene, Bcl-x, splicing in diabetic kidney disease. In 2019, Megan was awarded the Diabetes Centre of Excellence Consumables Award (2 years) to continue her research.

In 2021, Megan began a 3-year MRC-funded Postdoctural research project with Dr Benjamin Housden. Her research focus has shifted slightly to the use of combinatorial screening methods to identify novel drugs for the treatment of Neurofibromatosis type 1 in a Drosophila cell model. 

Links

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Research

Research interests

A major goal of Megan's current work is to identify new drugs that can be used either alone or in combination to effectively kill NF1 tumour cells, without causing side effects. To achieve this, we have used a novel approach in which we perform genetic screens in insect cells to identify genes that kill NF1-mutant cells. We then filter the results from these screens using human NF1-mutant cells. By assessing in these two very different systems, we are able to identify the most robust candidate drug targets for further development. By focusing on repurposed drugs, we are able to accelerate the development process in order to provide effective therapies to patients in the shortest time possible.

Research projects

Megan is currently working on an MRC-funded postdoctural research project awarded to Dr Housden on the identification of novel drug targets for the treatment of NF1 using combinatorial screening in a Drosophila NF1 mutant model.

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Publications

Journal articles

Brooks H, Li L, Addeo A, Stevens M, Comins C, Oltean S (2023). Detection of genomic mutations in blood and urine free circulating tumour DNA in patients with inoperable and metastatic lung adenocarcinoma harbouring an EGFR mutation in tissue: a UK pilot study. Frontiers in Oncology, 13 Abstract.
Li L, Zheng J, Stevens M, Oltean S (2022). A repositioning screen using an FGFR2 splicing reporter reveals compounds that regulate epithelial-mesenchymal transitions and inhibit growth of prostate cancer xenografts. Mol Ther Methods Clin Dev, 25, 147-157. Abstract.  Author URL.
Ayine ML, Stevens M, Oltean S (2022). IDF21-0319 Novel compounds found to regulate VEGF-A alternative splicing in diabetic podocytes. Diabetes Research and Clinical Practice, 186
Finch NC, Fawaz SS, Neal CR, Butler MJ, Lee VK, Salmon AJ, Lay AC, Stevens M, Dayalan L, Band H, et al (2022). Reduced Glomerular Filtration in Diabetes is Attributable to Loss of Density and Increased Resistance of Glomerular Endothelial Cell Fenestrations. J Am Soc Nephrol, 33(6), 1120-1136. Abstract.  Author URL.
Star E, Stevens M, Gooding C, Smith CWJ, Li L, Ayine ML, Harper SJ, Bates DO, Oltean S (2021). A drug-repositioning screen using splicing-sensitive fluorescent reporters identifies novel modulators of VEGF-A splicing with anti-angiogenic properties. Oncogenesis, 10(5). Abstract.
Kikuchi R, Stevens M, Harada K, Oltean S, Murohara T (2019). Anti-angiogenic isoform of vascular endothelial growth factor-A in cardiovascular and renal disease. , 88, 1-33. Abstract.
Stevens M, Oltean S (2019). Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis. Cells, 8(4). Abstract.  Author URL.
Stevens M, Oltean S (2019). Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. FRONTIERS IN GENETICS, 10  Author URL.
Stevens M, Star E, Lee M, Innes E, Li L, Bowler E, Harper S, Bates DO, Oltean S (2019). The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess the effects of splicing regulatory compounds in vivo. RNA Biol, 16(12), 1672-1681. Abstract.  Author URL.
Stevens M, Neal CR, Craciun EC, Dronca M, Harper SJ, Oltean S (2019). The natural drug DIAVIT is protective in a type II mouse model of diabetic nephropathy. PLoS One, 14(3). Abstract.  Author URL.
Stevens M, Payne M, Innes E, Torregrossa RO, Wood M, Stevens MKO, Whiteman MO, Oltean SO (2018). A novel mitochondria‐targeted hydrogen sulfide delivery molecule prevents uraemia and diabetes‐induced renal cell oxidative stress. The FASEB Journal, 32(S1), 619.10-619.10.
Stevens M, Oltean S (2018). Assessment of Kidney Function in Mouse Models of Glomerular Disease. J Vis Exp(136). Abstract.  Author URL.
Stevens M, Oltean S (2018). Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease. Genes (Basel), 9(2). Abstract.  Author URL.
Stevens M, Neal CR, Salmon AHJ, Bates DO, Harper SJ, Oltean S (2018). Vascular Endothelial Growth Factor-A165b Restores Normal Glomerular Water Permeability in a Diphtheria-Toxin Mouse Model of Glomerular Injury. Nephron, 139(1), 51-62. Abstract.  Author URL.
Stevens M, Neal CR, Salmon AHJ, Bates DO, Harper SJ, Oltean S (2017). VEGF-A165 b protects against proteinuria in a mouse model with progressive depletion of all endogenous VEGF-A splice isoforms from the kidney. J Physiol, 595(19), 6281-6298. Abstract.  Author URL.
Stevens M, Oltean S (2016). Alternative Splicing in CKD. J Am Soc Nephrol, 27(6), 1596-1603. Abstract.  Author URL.
Oltean S, Qiu Y, Ferguson JK, Stevens M, Neal C, Russell A, Kaura A, Arkill KP, Harris K, Symonds C, et al (2015). Vascular Endothelial Growth Factor-A165b is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy. J Am Soc Nephrol, 26(8), 1889-1904. Abstract.  Author URL.

Conferences

Brooks H, Addeo A, Comins C, Stevens M, Li L, Wade L, Oltean S (2019). Detection of Genomic Mutations in Blood and Urine ctDNA in Lung Adenocarcinoma with EGFR Mutation on Tissue - an Interim Progress Report.  Author URL.
Stevens M, Payne M, Innes E, Torregrossa RO, Wood M, Stevens MKO, Whiteman MO, Oltean SO (2018). A novel mitochondria-targeted hydrogen sulfide delivery molecule prevents uraemia and diabetes-induced renal cell oxidative stress.  Author URL.

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External Engagement and Impact

Editorial responsibilities


Conferences and invited presentations

  • The International Splicing Conference 2020, Lisbon, Portugal.
  • Poster at the European Diabetic Nephropathy Study Group 2019, Paris, France.
  • British Microcirculation Society 2019, Exeter, UK.
  • RNA Splicing 2019, Lake District, UK.
  • Diabetic Complications 2018, Osaka, Japan.
  • The International Splicing Conference 2018, Lisbon, Portugal.
  • RNA Splicing 2017, Lake District, UK.
  • The International Splicing Conference 2016, Lisbon, Portual.

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Supervision / Group

Postgraduate researchers

  • Monica Lamici Ayine PhD Student
  • Kyle Hoggard
  • Alex Marsh
  • Jinxia Zheng

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