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Biography

Dr Stephen Yarwood is an Associate Professor in the Institute of Biological Chemistry, Biophysics and Bioengineering (IB3) at Heriot-Watt University (HWU). He obtained his PhD in Biochemistry from the University of Glasgow in 1998. His research interests have been aimed at elucidating the molecular mechanisms underlying inflammatory disease states, like atherosclerosis, which are normally associated with diet-induced obesity and aging. In particular, his research has focused on understanding the mechanisms regulating cAMP signal transduction, particularly the EPAC1/Rap1 signalling system in the control of vascular inflammation, and has a proven record of accomplishment in defining the mechanisms of EPAC1 signalling (H-index 30, >£2M RCUK/British Heart Foundation (BHF) funding).

Research interests

Age-associated illnesses, eg cancers, cardiovascular and pulmonary diseases, neurological diseases (including Alzheimer's), diabetes, sarcopenia and autoimmune diseases, exhibit deregulation of multiple cell signalling pathways that have been linked to a sustained low-grade pro-inflammatory state. This is due to defective termination/resolution mechanisms, leading to increased levels of pro-inflammatory cytokines in the circulation, including IL-6 which leads to chronic inflammation. For example, cancers of immune and epithelial cells have a significant inflammatory component that drives proliferation, survival and pathogenic angiogenesis. These chronic diseases are the cause of 63% of all deaths worldwide and have an incidence that increases with age; consequently they account for around 70% of all healthcare spending.

We therefore need to understand fully the chronic inflammatory mechanisms associated with age if we are to maintain lifelong health and well-being in developed and developing societies. There is therefore an urgent need to identify new drug targets and develop new medicines that can prevent or reduce the chronic inflammation associated with these conditions, with the aim of improving quality of life of affected individuals. Our efforts to develop small molecules to combat age-related disease are a significant step towards this goal.

A chemical called "cyclic AMP", which is widely found in the cells of the body, normally protects the cells lining blood vessels (VECs) against the forms of inflammation associated with the development of heart disease. Current anti-inflammatory pharmaceuticals that globally elevate cyclic AMP levels (e.g. roflumilast for chronic obstructive pulmonary disorder) have undesirable side effects (eg vomiting and diarrhoea) that could be minimised by more targeted drugs that selectively and specifically activate cyclic AMP's anti-inflammatory mechanisms.

Central to the protective actions of cyclic AMP is an enzyme, EPAC1, which suppresses multiple inflammatory signalling pathways in VECs, through selective changes in gene activity. We have discovered drug-like molecules (NCN EPAC1 agonists) that activate EPAC1 in VECs and inhibit the inflammation caused by IL-6. Our aims are to determine the mechanisms of actions of NCN EPAC1 agonists, which is part of our long-term goal of transferring a detailed molecular understanding of processes that protect against chronic inflammation into new therapeutic strategies. 

External positions

University of Glasgow

19992015

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  • 1 Similar Profiles
Cyclic AMP Medicine & Life Sciences
Phosphoric Diester Hydrolases Medicine & Life Sciences
Proteins Medicine & Life Sciences
Cytokines Medicine & Life Sciences
Cyclic AMP-Dependent Protein Kinases Medicine & Life Sciences
Genes Medicine & Life Sciences
Endothelial Cells Medicine & Life Sciences
Protein Isoforms Medicine & Life Sciences

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

Research Output 1995 2019

5 Downloads (Pure)

Genome-Wide Mapping Defines a Role for C/EBPβ and c-Jun in Non-Canonical Cyclic AMP Signalling

Wiejak, J., van Basten, B., Hamilton, G. & Yarwood, S. J., 14 Oct 2019, In : Cells. 8, 10, 1253.

Research output: Contribution to journalArticle

Open Access
File
Chromosome Mapping
Cyclic AMP
Rolipram
Interleukin-6
Colforsin
4 Downloads (Pure)

Identification of A Novel Class of Benzofuran Oxoacetic Acid-Derived Ligands that Selectively Activate Cellular EPAC1

Beck, E. M., Parnell, E., Cowley, A., Porter, A., Gillespie, J., Robinson, J., Robinson, L., Pannifer, A. D., Hamon, V., Jones, P., Morrison, A., McElroy, S., Timmerman, M., Rutjes, H., Mahajan, P., Wiejak, J., Luchowska-Stańska, U., Morgan, D., Barker, G., Rehmann, H. & 1 others, Yarwood, S. J., 12 Nov 2019, In : Cells. 8, 11, 1425.

Research output: Contribution to journalArticle

Open Access
File
GTP Phosphohydrolases
Cyclic Nucleotides
Nucleotides
High-Throughput Screening Assays
Ligands
11 Downloads (Pure)

Selective small-molecule EPAC activators

Luchowska-Stańska, U., Morgan, D., Yarwood, S. J. & Barker, G., 11 Oct 2019, In : Biochemical Society Transactions. 47, 5, p. 1415-1427 13 p.

Research output: Contribution to journalArticle

Open Access
File
Cyclic Nucleotides
Adenosine Monophosphate
Cyclic AMP-Dependent Protein Kinases
Vascular Resistance
Cyclic AMP
18 Downloads (Pure)
Open Access
File
Umbilicus
Cyclic AMP
Endothelial Cells
Gene Expression
Proteins
48 Downloads (Pure)

Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1

Parnell, E., McElroy, S. P., Wiejak, J., Baillie, G. L., Porter, A., Adams, D. R., Rehmann, H., Smith, B. O. & Yarwood, S. J., 22 Mar 2017, In : Scientific Reports. 7, 294.

Research output: Contribution to journalArticle

Open Access
File

Prizes

Human Frontiers Science Program Fellowship

Stephen John Yarwood (Recipient), 1999

Prize: Fellowship awarded competitively

Activities 1999 2020

External PhD Examination

Stephen John Yarwood (Examiner)
2020

Activity: Examination

Editor of Special Edition of Cells (New Advances in Cyclic AMP Signaling) (Event)

Stephen John Yarwood (Editorial board member)
2019

Activity: Publication peer-review and editorial workEditorial activity

Nanodomains in cyclic nucleotide signalling: from mechanisms to therapeutic approaches

Stephen John Yarwood (Invited speaker)
2019

Activity: Participating in or organising an eventParticipation in conference

Cells (Journal)

Stephen John Yarwood (Editorial board member)
2019

Activity: Publication peer-review and editorial workEditorial activity

Internal PhD Examination

Stephen John Yarwood (Examiner)
2018

Activity: Examination

Press / Media

Press Releases on Flavanoid Research

Stephen Yarwood

12/08/1313/08/16

9 items of Media coverage

Press/Media: Research