My main area of research focuses predominantly on diabetic nephropathy, renal disease and gap junction mediated cell-to-cell communication in the diseased kidney. Specifically I am interested in how a loss of cell-to-cell communication may facilitate the progression of renal fibrosis through modulation of the extracellular matrix and disrupted cell-to-cell adhesion. Other research projects include; understanding the role and regulation of ketamine in renal and bladder fibrosis.
1998-2001 BSc Medical Bioscience, University of Kent (1st class)
2001-2002 Project Scientist, Pfizer Pharmaceuticals, (Kent).
2002-2006 PhD Molecular Physiology, University of Warwick
2006-2009 PDRA, Department of Infection, Immunity & Inflammation, University of Leicester.
2009-2011 Wellcome Trust VIP Research Fellow, School of Life Sciences, University of Warwick
2011-2013 Research Fellow University of Warwick
2013-2014 Senior Research Fellow, University of Warwick
2014- 2016 Senior Research Fellow, University of Lincoln
2016 -2017 Senior Lecturer, University of Lincoln
2017- Reader, University of Lincoln
In collaboration with Professor Squires we are interested in several aspect of glucose and TGF-beta induced renal damage in diabetes. Almost one third of all patients with diabetes progressively develop diabetic nephropathy (DN) within 10-to-30 years of the onset of disease and DN accounts for almost a quarter of those entering end-stage renal replacement programs in the UK. However, we still lack a basic understanding of this debilitating condition. Current dogma implicates the cytokine transforming growth factor beta (TGF-beta;) as the predominant mediator of tubulointerstitial fibrosis, the common final pathway in DN and end-stage renal disease. Understanding the mechanism by which TGF-beta instigates phenotypic and morphological changes is essential in establishing novel therapeutic strategies for the prevention or arrest of the disease. Our studies aim to elucidate how TGF-beta; disrupts cell-adhesion, cell-cell communication and renal function in DN. The work is funded by Diabetes UK, the EFSD, DRWF, the Physiological Society and the WPH Charitable Trust.
Urological complications of ketamine abuse:
In the UK, Ketamine or Special K is fast becoming the “party drug” of choice amongst 16-24 year olds and as its popularity increases we are becoming aware of serious side effects, including renal and ureteral damage. This project investigates how ketamine promotes tissue fibrosis and scarring. Epithelial function depends on complex cell-cell interactions, and our studies examine how ketamine alters the expression and localisation of key adhesion protein ahead of a functional loss in cell-cell coupling and a desolution of connexin-mediated gap-junctions. Loss in cell-cell adhesion represents early pathological changes ahead of overt complications of ketamine abuse e.g. fibrosis and may represent a possible target for future therapeutic intervention. This project is funded by the Rosetree Trust.
Cyclosproin A in renal fibrosis:
Cyclosporin A (CsA) is an immunosuppressant drug, which has been used to improve graft survival in renal transplantation through suppression of the immune response. However CsA is marred by acute and chronic nephrotoxicity. Studies have confirmed that exposure of renal tubular cells to CsA evokes key morphological and phenotypic changes characteristic of epithelial-to-mesenchymal transition (EMT). This process is associated with the loss in expression of epithelial markers and gain in expression of those more commonly associated with a fibroblast phenotype. Ultimately, as cell undergo EMT they undergo a loss in cell adhesion and detachment from the tubular basement membrane, they subsequently acquire a migratory phenotype migrate into the interstitum where they reside as active myofibroblasts. The transition of cells through EMT in response to high circulating levels of CsA is thought to represent the key underlying pathology behind the development of renal fibrosis in patients having undergone kidney transplantation. Our work on CsA in the proximal tubule aims to address the relationship between CsA and the expression of key candidate proteins in the proximal tubule central to cell-to-cell adhesion and cell matrix interaction. This project is funded by the Petroleum Technology Development Fund.
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MEMBERSHIP OF LEARNED SOCIETIES
Member of the European Association for the Study of Diabetes
Member of Diabetes UK
Member of the Physiological Society
Member of Society for Endocrinology
RESEARCH RELATED ACTIVITIES
Abstract reviewer for the British Renal Association.
Manuscript reviewer for numerous kidney and diabetes journals including Diabetolgia, PLOS, American Journal of Nephrology, Molecular Endocrinology, JASN