Exposure to maternal undernutrition in early life directly impacts upon fetal growth and development and permanently alters postnatal physiology. This has been demonstrated to predispose individuals towards cardiovascular disease, diabetes and obesity in adulthood. An important aspect of these phenotypes is that they are both permanent and worsen with age. My current research seeks to examine the role of epigenetic modifications, most notably DNA methylation, brought about by in utero exposure to maternal undernutrition, in programming insulin resistance and how this might be modulated by ageing. In addition, I am also interested in understanding the mechanisms by which fetal growth impairment results in alterations in cellular determination during development.
Acute kidney injury.
Acute Kidney Injury (AKI) is defined as an abrupt decline in kidney function. It is common, occurring in up to 7% of acute hospital admissions and extremely serious with >50% mortality when occurring on Intensive Care Unit. The incidence of AKI in the general population has been estimated to be as high as 750000/year (Health Service Journal supplement 23 June 2011). This is the equivalent of the entire population of Leeds (3rd largest city) or 10% of the population of London suffering from an episode of AKI annually. Treatment is supportive, with optimization of fluid balance and blood pressure, avoidance of nephrotoxins and institution of renal replacement therapy where necessary. A single episode of AKI requiring hospital admission increases the likelihood of that individual further suffering chronic kidney disease (CKD) and end-stage renal disease (ESRD). We have recently begun to examine putative therapeutic interventions aimed at both preventing AKI and/or enhancing recovery from an episode of AKI. We are currently in the process of establishing a number of in vitro models of AKI to enable examination of cellular responses in both single cell type and multiple cell type environments.
The processes by which the metanephric, or true kidney is formed are incompletely understood. Many of these processes, if aberrantly impacted upon, result either in inadequate renal development, often leading to a nephron deficit, or more severely, renal malformations for which the only useful treatment is transplant. One of the areas of renal development which we are interested in understanding is the process of cellular migration within the "stem" population of nephron progenitor cells (i.e. those which will go on to form nephrons). By elucidating the mechanisms which control both the rate and direction of migration of these cells, we hope to reveal how the structure of the kidney is established and, importantly, the processes which mediate cessation of renal development.
Additional research interests:
Novel modes of dietary monitoring.
Development of alternative means of dietary selection/choice.
Insects as food for humans and livestock.
Cellular amino acid requirements.
GARDNER DS, DE BROT S, DUNFORD LJ, GRAU-ROMA L, WELHAM SJ, FALLMAN R, O'SULLIVAN SE, OH W and DEVONALD MA, 2015. Remote effects of acute kidney injury in a porcine model. American journal of physiology. Renal physiology. 310(4), F259-71
GARDNER DS, WELHAM SJM, DUNFORD LJ, MCCULLOCH TA, HODI Z, SLEEMAN P, O'SULLIVAN S and DEVONALD MAJ, 2014. Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism? American journal of physiology. Renal physiology. 306(8), F873-84