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    United Kingdom

Accepting PhD Students

19962019
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Personal profile

Research Interests

The aim of my research is to provide a better understanding of the causes of eye and vascular diseases. This is achieved by application of advanced molecular biology approaches to provide novel insights. This enables both development of new treatments and design of improved diagnostic and prognostic tests. The specific areas of interest are outlined below.

Retinal gene expression and ophthalmic genetics

A key focus of my research has been to study changes in gene expression, specifically the response of the retina to ischaemic conditions. A key finding was that members of the VEGF family of growth factors, which regulate neovascularisation, are differentially regulated during hyperoxia and hypoxia. Analysis of VEGF splicing demonstrated that previously reported anti-angiogenic VEGF isoforms are PCR artefacts and do not exist in vivo. I have also studied the broader regulation of gene expression in the retina, specifically the changes involved in diabetes and during pathogenic neovascularisation. This work has contributed to understanding of the pathogenesis of vasodegeneration in diabetic retinopathy and retinopathy of prematurity.

In tandem with studying gene expression in the retina I have also investigated mutations in genes which cause retinal degeneration, specifically inherited retinal diseases such as Retinitis Pigmentosa (RP). This has involved the discovery of novel mutations and the development of a custom re-sequencing genechip which has been used to detect known and novel mutations in the Northern Irish RP population. I was one of the first to exploit next generation sequencing (NGS) techniques to screen panels of candidate genes. My key conclusion from this work is that, from both technical and financial viewpoints, it is now possible to develop a routine diagnostic screening tool which would be vastly superior to the current individual gene sequencing tests.

MicroRNAs

The discovery of the importance of microRNAs (miRNAs) in regulating gene expression to control developmental pathways and other cellular functions led me to investigate their role in the retina. A fascinating feature of miRNAs is that they can each regulate multiple messenger RNAs (mRNAs) and conversely each mRNA can be targeted by multiple miRNAs. The regulatory load on a specific mRNA is therefore a combinatorial effect of those miRNAs that are both expressed in the cell and have target sites in the 3' UTR of that mRNA. I showed that it was possible to determine which miRNAs are likely to play an important role in the retina by analysing those miRNAs predicted to target genes with retinal functions: It was confirmed that many of these miRNAs were expressed in the retina and that some of the predicted interactions did occur. The concept of analysing mRNA expression to determine information about concomitant miRNA expression was extended by development of an algorithm to detect the ‘signature' which miRNAs exert upon a global gene expression profile (published in Genome Biology). The elevated expression of those miRNAs shown to have a significant effect upon mRNA expression demonstrated the efficacy of this approach.

The advent of NGS and RNA Sequencing made it possible to profile global RNA expression profiles. I was amongst the first to apply this technique to catalogue microRNAs in the retina and retinal endothelial cells. MicroRNAs are released from cells in extracellular vesicles and may be transferred to other cells and mediate cell to cell communication. I used small RNA-Sequencing to show that specific microRNAs are exported in these vesicles and demonstrated the potential use of vesicles as a therapeutic to treat retinal neovascularisation.

MicroRNAs released from cells are stable in the blood, making them attractive biomarkers. I am currently using NGS to profile small RNAs in blood and urine as potential prognostic markers for cardiovascular disease.

Single cell RNA-Sequencing (scRNA-Seq)

My experience in molecular biology enabled me to immediately recognise the potential of NGS. I have been instrumental in establishing the Faculty Genomics Core Technology Unit which provides access to NGS technology within the University. Most recently I have led development of single cell RNA-Sequencing and am applying this new technology to a range of pathologies, specifically to study how individual cells in the retina are affected by diabetes as an approach to find new ways to treat the disease. The increasing number of publications based on scRNA sequencing has confirmed the transformative nature of this technology and I anticipate that it will form a significant part of my research in the future.

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  • 36 Similar Profiles
MicroRNAs Medicine & Life Sciences
Retina Medicine & Life Sciences
Retinitis Pigmentosa Medicine & Life Sciences
High-Throughput Nucleotide Sequencing Medicine & Life Sciences
Vascular Endothelial Growth Factor A Medicine & Life Sciences
Genes Medicine & Life Sciences
Mutation Medicine & Life Sciences
Retinal Vessels Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects 2009 2019

Research Output 1996 2019

1 Citation (Scopus)

A comparison of RNA extraction and sequencing protocols for detection of small RNAs in plasma

Wong, R. K. Y., MacMahon, M., Woodside, J. V. & Simpson, D. A., 03 Jun 2019, In : BMC Genomics. 20, 12 p., 446.

Research output: Contribution to journalArticle

Open Access
File
RNA Sequence Analysis
MicroRNAs
RNA
Libraries
Biomarkers
Open Access
File
Diabetic Nephropathies
MicroRNAs
Type 2 Diabetes Mellitus
Kidney
Chronic Renal Insufficiency
1 Citation (Scopus)

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

Vilà-González, M., Kelaini, S., Magee, C., Caines, R., Campbell, D., Eleftheriadou, M., Cochrane, A., Drehmer, D., Tsifaki, M., O'Neill, K., Pedrini, E., Yang, C., Medina, R., McDonald, D., Simpson, D., Zampetaki, A., Zeng, L., Grieve, D., Lois, N., Stitt, A. W. & 1 othersMargariti, A., 17 Nov 2018, In : Stem Cells.

Research output: Contribution to journalArticle

Open Access
File
Induced Pluripotent Stem Cells
Endothelial Cells
Vascular Diseases
Preclinical Drug Evaluations
Cell- and Tissue-Based Therapy
8 Citations (Scopus)
Open Access
File
MicroRNAs
Endothelial Cells
RNA Sequence Analysis
Extracellular Vesicles
Microarray Analysis
2 Citations (Scopus)

RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms

Bridgett, S., Dellett, M. & Simpson, D. A., 03 Mar 2017, In : Scientific Reports. 7, 11 p., 58.

Research output: Contribution to journalArticle

Open Access
File
RNA Sequence Analysis
Vascular Endothelial Growth Factor A
Protein Isoforms
Exons
Polymerase Chain Reaction

Activities 1998 2015

Invited presentation at mininsymposium, ARVO 2015

David Simpson (Speaker)
03 May 2015

Activity: Talk or presentation typesInvited talk

Invited presentation at 10th International MicroRNAs/Non-Coding RNAs & Genome Editing Europe – 2015 Meeting

David Simpson (Chair)
02 Nov 2015

Activity: Talk or presentation typesInvited talk

Invited presentation at qPCR & NGS 2015

David Simpson (Speaker)
23 Mar 201527 Mar 2015

Activity: Talk or presentation typesInvited talk

Presentation in ARVO Education Course 'microRNA and Ocular Disease'

David Simpson (Contributor)
04 May 2013

Activity: Talk or presentation typesInvited talk

Invited presentation at 2nd Irish Next Generation Sequencing/Bioinformatics Meeting

David Simpson (Speaker)
31 May 2012

Activity: Talk or presentation typesInvited talk