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Jonathan D. Turner

PI - Immune Endocrine Epigenetics
Deputy Director, Allergology, Immunology, Inflammation
Department of Infection and Immunity,
Luxembourg institute of Health
Esch-sur-Alzette
Grand Duchy of Luxembourg
jonathan.turner@lih.lu
Stress represents the single most important cause of disease, causing costs as high as 3-4 % of the European GNP, and up to 60% of all work-days lost to disease. Many of these diseases are related to infections and aberrant immune reactions. Our interest is in elucidating genetic, epigenetic, transcriptional, translation and post-translational mechanisms underlying environmental control of the stress reaction, and to understand how this contributes to the environmental control of phenotype development.

We have extensively studied the transcriptional and translational regulation of the glucocorticoid receptor (GR) as one of the main mediators of the stress response system, the hypothalamic-pituitary-adrenal (HPA). The GR mediates the HPA feed-back and is responsible for homeostasis of many cell and organ functions including inflammatory and immune processes, in particular during stress. Mechanisms underlying the transcriptional and translational control of the human GR and its activity on a molecular level help to understand the interaction between the central nervous system, the HPA axis and the immune system under stress. Using chronic restraint and psychosocial stress models we successfully programmed the HPA axis is rats, particularly through increased GR promoter methylation in peripheral HPA axis tissues. To assess the effects of epigenetic programming of GR promoters on HPA axis function in man, we have developed a mathematical deconvolution model of the HPA axis, accessing and characterizing cortisol secretion from the adrenal gland using saliva, a sampling technique that has the advantage of not activating the HPA axis.

Our current focus is on the lifelong effects of epigenetic programming. We are currently focussed on two epigenetic programming events, early life immune challenge (ELIC) and adversity (ELA). Both paradigms affect HPA axis reactivity, and share many long term effects. After ELIC, the reaction to subsequent immune challenge was reduced. This diminished response was accompanied by increased global methylation levels, and was transmitted to subsequent untreated generations. We are currently recruiting ELA individuals that were adopted during the 1990s from orphanages worldwide. Preliminary data shows that our ELA subjects have reduced HPA axis and an increased immune response to stress. In this project we are collecting genome wide MeDIP-Seq, environmental, behavioural, and psychological data, as well as functional data on the status of their immune, cardiovascular and stress response systems. Integrating these data will provide a broad and unique insight on the influence of ELA on the development of adult disease.

Collaborations:

“Forschungsinstitut für Psychobiologie des Stresses” University Trier,
Research Unit INSIDE, University of Luxembourg
Leiden-Amsterdam Centre for Drug Research (LACDR)
Department of Periodontology University of Oslo & Department of Medical Psychology, Bergen, Norway


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