Professor Stafford Lightman

Summary

Stress related disease is a rapidly increasing feature of our society - but the mechanisms through which it causes disease are very poorly understood.

We are studying the mechanisms through which the brain recognises environmental stress and disease, and the pathways it uses to initiate appropriate responses in physiological regulation and gene transcription.  We have been particularly interested in the way the body utilises rhythmic activation of neuroendocrine response systems such as the hypothalamo-pituitary-adrenal axis to provide digital as well as analogue signals to glucocorticoid responsive tissues throughout the body.

In my clinical studies, we are developing novel ways of administrating glucocorticoid replacement to patients with adrenal insufficiency and have been developing systems to assess stress responses in disease and in patients undergoing surgery.

Activities / Findings

• The effects of stress on the pulsatile secretion of the hypothalamo-pituitary-adrenal axis
• The neural pathways involved in the response to inflammatory and psychological stressors (with Dr Chris Lowry)
• Mechanisms of specificity of corticosteroid effects in different tissues and the differential responses of splice variants of the glucocorticoid receptor (with Dr Michael Norman)
• Assess the mechanisms through which stress can accelerate atheroma formation in Apo(e)-- knockouts (with Dr Chris Jackson)
• Studies in cohorts of subjects to assess stress reponsiveness and its correlation with clinical endpoints of disease

Teaching

MSc in Molecular Neuroscience,undergraduate lectures and clinical teaching

Keywords

• Circadian and ultradian rhythms
• Hypothalamo-pituitary-adrenal axis
• Glucocorticoid signalling

Skills

• Stress related disorders
• Depression
• Sleep apnoea
• Addison’s disease
• Cushing’s disease

Processes and functions

• Novel treatments of stress related disease including clinical depression and anxiety disorders
• Origin of hormonal pulsatility
• Modulation of glucocorticoid signalling in disease

Methodologies

• Molecular techniques for gene expression
• Immunocytochemistry
• Radioimmunoassay
• Automated blood sampling
• Behavioural studies
• Clinical studies

Memberships

Organisations

School of Clinical Sciences

Other sites

• Clinical-sciences
• Neuroscience

Selected publications

• Walker, J, Terry, J & Lightman, S 2010, ‘Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis’. Proceedings of the Royal Society B: Biological Sciences, vol 277., pp. 1627 - 1633
• Lightman, S & Conway-Campbell, B 2010, ‘The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration’. Nat Rev Neurosci, vol 11., pp. 710 - 718
• Stavreva, DA, Wiench, M, John, S, Conway-Campbell, B, McKenna, M, Pooley, J, Johnson, TA, Voss, TC, Lightman, S & Hager, GL 2009, ‘Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription’. Nat Cell Biol, vol 11., pp. 1093 - 1102
• Conway-Campbell, B, Pooley, J, Hager, G & Lightman, S 2012, ‘Molecular dynamics of ultradian glucocorticoid receptor action’. Mol Cell Endocrinol, vol 30;348(2)., pp. 383 - 393
• Biddie, S, John, S, Sabo, P, Thurman, R, Schiltz, R, Johnson, T, Sung, M, Trump, S, Lightman, S, Vinson, C, Stamatoyannopoulos, J & Hager, G 2011, ‘Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding’. Mol Cell, vol 43 (1)., pp. 145 - 155
• Conway-Campbell, B, George, C, Pooley, J, Knight, D, Norman, M, Hager, GL & Lightman, S 2011, ‘The HSP90 molecular chaperone cycle regulates cyclical transcriptional dynamics of the glucocorticoid receptor and its co-regulatory molecules CBP/P300 during ultradian ligand treatment’. Molecular Endocrinology, vol 25., pp. 944 - 954
• Spiga, F, Waite, E, Liu, Y, Kershaw, Y, Aguilera, G & Lightman, S 2011, ‘ACTH-Dependent Ultradian Rhythm of Corticosterone Secretion’. Endocrinology, vol 152(4)., pp. 1448 - 1457
• Sarabdjitsingh, RA, Conway-Campbell, B, Leggett, J, Waite, E, Meijer, OC, Kloet, ERd & Lightman, S 2010, ‘Stress responsiveness varies over the ultradian glucocorticoid cycle in a brain-region-specific manner’. Endocrinology, vol 151., pp. 5369 - 5379
• Atkinson, H, Leggett, J, Wood, S, Castrique, E, Kershaw, Y & Lightman, S 2010, ‘Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic’. Endocrinology, vol 151 (8)., pp. 3720 - 3727
• Cameron, G, Henley, D, Carrell, R, Zhou, A, Clarke, A & Lightman, S 2010, ‘Temperature-responsive release of cortisol from its binding globulin: A protein thermocouple’. The Journal of Clinical Endocrinology & Metabolism, vol 95 (10)., pp. 4689 - 4695

Read more >

View complete publications list in the University of Bristol publications system

Networks & contacts

• Professor John Terry - University of Exeter
• Dr Gordon Hager - National Institutes of Health
• Dr Greti Aguilera - National Institutes of Health
• Professor Kevin O’Byrne - King’s College London
• Professor Iain Clarke - Monash University