Personal profile

Biography

Stephen Yarwood obtained his PhD from the University of Glasgow in 1998 based on work carried out at the Hannah Research Institute on the control of fat cell development. Following this he undertook a three year Post-Doctoral Fellowship in the laboratory of Professor Miles Houslay, studying protein-protein interactions within the cyclic AMP signalling pathway. After being appointed to a Lectureship in the University of Glasgow in 1999, he took research leave, funded by a Human Frontiers Science Program Fellowship (November 1999-January 2001), in the laboratory of Professor Jim Woodgett, at the Ontario Cancer Institute, Toronto, Canada. There he investigated the impact of extracellular matrix on global gene expression patterns in cells undergoing growth factor treatment. After returning to Glasgow from Canada his research was aimed at understanding the molecular control of disease processes by cyclic AMP, including chronic inflammation associated with atherosclerosis and bone health associated with diabetes. In 2016 he moved to an Associate Professor postition at Heriot-Watt University, Edinburgh, where he continues his investigations into the molecular control of cyclic AMP signalling in health and disease.

Research interests

Research in the Yarwood lab is centered on the field of cyclic AMP signalling, particularly the role of exchange protein activated by cyclic AMP (EPAC) sensor proteins in the control of health and disease.

Our most recent objective has been to understand the fundamental molecular mechanisms underlying the attenuation of inflammatory signalling mediated by the EPAC1 isoform in vascular endothelial cells (VECs). From this work we have defined SOCS3 induction as a new paradigm for cyclic AMP-mediated transcriptional control and suppression of pro-inflammatory interleukin 6 (IL-6) signalling (eg Wiejak et al, 2014; Wiejak et al, 2013; Wiejak et al, 2012; Borland et al, 2009; Yarwood et al, 2008). Our current work is aimed at understanding how tethering of EPAC1 to the nuclear pore complex in VECs underlies the induction of multiple regulatory genes, including the SOCS3 gene, which are involved in the suppression of pro-inflammatory cytokine signalling.

Given the importance of EPAC1 in the control of disease processes, a number of drug discovery programmes have now been initiated to identify small molecule regulators of EPAC activity in cells. This approach displays a reduced risk of side-effects compared with general cyclic AMP-elevating agents, such as type 4 cyclic AMP phosphodiesterase (PDE) inhibitors, which activate multiple response pathways. We have also initiated ultra high throughput-screening (uHTS) protocols to identify EPAC regulators in collaboration with the European Screening Centre at Newhouse, Scotland and the European Lead Factory. We have already identified a number of hits in primary HTS that are effective EPAC antagonists. We have generated preliminary data demonstrating that these novel compounds can regulate the differentiation of mesenchymal stem cells (MSCs) from fat- to bone-forming cells and may therefore be effective in helping to maintain bone health in diseases, such as diabetes, where there is impairment in bone density. This work complements ongoing work in my laboratory, funded by Tenovus Scotland, which is aimed at discovering the mechanisms of actions of anti-diabetic drugs, such as metformin and regulators of free fatty acid (FFA) G-protein coupled receptors, in the control of MSC differentiation.

An additional research interest we have is the interaction of cells with synthetically engineered nanometric growth surfaces, carried out in collaboration with Professor Matt Dalby at the Centre of Cell Engineering, University of Glasgow. This work grew from our long-term interest in the control of cell morphology, through the actin and microtubular cytoskeletons, by EPAC proteins (Parnell et al, 2015; Parnell and Yarwood, 2014; Borland et al, 2006; Gupta and Yarwood, 2005; Mageira et al, 2004). The collaboration with Professor Dalby has given rise to a number of high profile collaborative publications (Wang et al, 2014; Wiejak et al, 2013; Dalby et al, 2008; Dalby et al, 2003; Dalby et al, 2002).  

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

Research Output 1995 2017

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
cyclic AMP
sensors
molecules
Molecules
Sensors

Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms

Chen, S. C., Brooks, R., Houskeeper, J., Bremner, S. K., Dunlop, J., Viollet, B., Logan, P. J., Salt, I. P., Ahmed, S. F. & Yarwood, S. J. 15 Jan 2017 In : Molecular and Cellular Endocrinology. 440, p. 57–68 12 p.

Research output: Contribution to journalArticle

Open Access
File
Adipogenesis
AMP-Activated Protein Kinases
Metformin
Proteins
protein

Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency

Lee, L. C. Y., Gadegaard, N., De Andrés, M. C., Turner, L-A., Burgess, K. E. V., Yarwood, S. J., Wells, J., Salmeron-Sanchez, M., Meek, R. M. D., Oreffo, R. O. C. & Dalby, M. J. Feb 2017 In : Biomaterials. 116, p. 10-20 11 p.

Research output: Contribution to journalArticle

Open Access
File
Cell Cycle Checkpoints
Stem Cells
Stem cells
stem
Cell culture

Probe-dependent negative allosteric modulators of the long-chain free fatty acid receptor FFA4

Watterson, K. R., Hansen, S. V. F., Hudson, B., Alvarez-Curto, E., Raihan, S. Z., Azevedo, C. M. G., Martin, G., Dunlop, J., Yarwood, S. J., Ulven, T. & Milligan, G. 1 Jun 2017 In : Molecular Pharmacology. 91, 6, p. 630-641 12 p.

Research output: Contribution to journalArticle

Open Access
File
Nonesterified Fatty Acids
G-Protein-Coupled Receptors
Mesenchymal Stromal Cells
Adipocytes
Type 2 Diabetes Mellitus
Open Access
File
Phosphoric Diester Hydrolases
Cyclic AMP
Phosphotransferases
Protein Kinase C
Proteins

Prizes

Human Frontiers Science Program Fellowship

Stephen John Yarwood (Recipient), 2000

Prize: Fellowship awarded competitively

Press / Media

Press Releases on Flavanoid Research

Stephen John Yarwood

12/08/1313/08/16

9 items of media coverage

Press / Media: Research