Edinburgh Research Explorer

Prof Megan Holmes

Personal Chair of Molecular Neuroendocrinology

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Phone: 0131 242 6737

Willingness to take Ph.D. students: Yes

My research in a nutshell

The hormonal response to stress is crucial for survival, yet chronic stress can lead to increased susceptibility to both cardiometabolic disease, as well as psychiatric and memory disorders. My research has focussed on the regulation of the normal response to stress through the hypothalamo-pituitary adrenal axis (Good Stress) and how this is can become dysregulated to cause disease (Bad Stress).  My main focus has been on the effect of stress or high glucocorticoids (cortisol in man or cortisosterone in rodents, as well as synthetic steroids such as dexamethasone) during vulnerable developmental periods (prenatal or postnatal) to ‘programme’ life-long changes in affective behaviour and memory and understand the mechanisms that underpin these effects. Such mechanistic studies allow development of novel therapies to alleviate or reverse the adverse consequences of the stress hormones.

 

Other interests include the underestimated importance of the brain in the regulation of blood pressure and salt appetite, and the consequences of stress particularly in development on the trajectory of cognitive decline with age.

 

A major component of our work involves the use of targeted rodent models, that have been developed in our laboratory. We also have developed state-of-the–art high resolution, in vivo imaging paradigms to provide non invasive functional imaging of behavioural responding animals using functional Magnetic Resonance Imaging (fMRI) and monitor feto-placental development (particularly of umbilical vessels and fetal heart) by high resolution ultrasound.

Biography

Both my BSc and PhD were carried out in London (Bedford college and St Thomas’s Hospital Medical School), were I studied Physiology and sparked my first interest in stress. I then obtained fellowships to work in the Hungarian Academy of Sciences in Budapest and then on to the National Institutes of Health, Bethesda, USA where I continued my work on the regulation of the HPA axis by the brain. After a career break, I joined the University of Edinburgh with ‘Return-to-work’ and Career development fellowships from the Wellcome Trust. Subsequently I obtained a faculty position and was promoted through the ranks to full Professor in 2008. My research has focussed on inter-relationship between glucocorticoids and the serotonergic system, the crucial role of the glucocorticoid metabolising enzymes, 11β-Hydroxysteroid dehydrogenases in regulating glucocorticoid effects both in the brain but also the periphery and the early-life programming of the brain by glucocorticoids.

Administrative Roles

Chair of Edinburgh Preclinical Imaging Research Committee

I oversee and direct the facilities within Edinburgh Preclinical Imaging (EPI), to provide the latest in vivo imaging technologies to researchers. EPI consists of 5 modalities suitable for imaging small animals: 7T Magnetic Resonance Scanner, PET/CT scanner, Ultrasound, Optical  and Laser-doppler blood flow. Information on the facilities and their use can be seen on the EPI website (http://www.ed.ac.uk/clinical-sciences/edinburgh-imaging/edinburgh-preclinical-imaging). EPI is part of Edinburgh Imaging which encompasses both Clinical and Preclinical Imaging.

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