13 Dec 21. Professor Megan Holmes retires

Professor Megan Holmes, Personal Chair of Molecular Neuroendocrinology will be retiring at the end of 2021. Edinburgh Imaging looks back at her career at the University.

Background and career

Professor Megan Holmes studied Physiology in London – for her BSc at Bedford College, then for her PhD at St Thomas’s Hospital Medical School. During this time, she first developed her interest in stress.

Professor Holmes went on to fellowships at the Hungarian Academy of Sciences in Budapest and the National Institutes of Health, Bethesda, USA. The focus of her fellowships was the regulation of the hypothalamo-pituitary adrenal (HPA) axis by the brain.

After a career break, she joined the University of Edinburgh with ‘Return-to-work’ and Career development fellowships from the Wellcome Trust. Subsequently, she obtained a faculty position and eventually reaching full Professorship in 2008.

Professor Holmes has overseen and directed the Edinburgh Preclinical Imaging (EPI) facilities, which delivers the latest in vivo imaging technologies to researchers.

Research

Professor Holmes’ 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).

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.

Professor Holmes’ main focus has been on the effect of stress, or high glucocorticoid levels: cortisol in man, cortisosterone in rodents, as well as synthetic steroids such as dexamethasone. She has focused on vulnerable developmental periods (prenatal or postnatal), to evaluate how glucocorticoids might ‘programme’ life-long changes in affective behaviour and memory. To understand mechanisms which underpin these effects, Prof Holmes carried out mechanistic studies which have allowed development of novel therapies to alleviate, or reverse, the adverse consequences of the stress hormones.

Other research interests of Professor Holmes have included the underestimated importance of the brain in blood pressure regulation and salt appetite, as well as what the consequences of stress are in cognitive decline with age.

A major component of Professor Holmes’ work has used targeted rodent models, which have been developed in her laboratory. Professor Holmes’ and her team have also developed state-of-the–art high resolution, in vivo imaging paradigms: one paradigm has used functional magnetic resonance imaging (fMRI) to acquire non-invasive functional images of behavioural responding animals; another has used high resolution ultrasound to monitor feto-placental development (particularly of umbilical vessels and the fetal heart).

Awards and achievements

The central theme of Prof Holmes research throughout her career has been ‘Stress’. Although 'stress' is a beneficial response, chronic stress can be a common cause of metabolic and brain disorders. Prof Holmes research has defined mechanisms by which glucocorticoids - an important class of stress hormone - lead to stress-related disorders, particularly of the brain. Her work has defined the mechanisms regulating glucocorticoid action at different stages of life, particularly in the brain. She showed that early life is a particularly sensitive period - a developmental window - when inappropriate exposure to stress hormones can alter susceptibility to metabolic and brain disease in later life. She demonstrated that high glucocorticoids alter placental function as well adversely affecting the developing fetal brain directly, with consequent deleterious effects on brain function as adults. She developed novel in vivo imaging of the adult rodent brain to demonstrate functional changes in the brain associated with stress.

In 2011, Prof Holmes established and became the inaugural Director of Edinburgh Preclinical Imaging (EPI) to provide in vivo imaging of small animals across the University. She is on the directorate of Edinburgh Imaging, which incorporates imaging facilities and expertise for human, large and small animal imaging across the University. Prof Holmes was instrumental in obtaining funding for the new 9.4T MR scanner and played a key role in obtaining funding for new preclinical ultrasound imaging to ensure the highest specification imaging can be carried out. She led the preclinical imaging theme for the Centre of Cognitive Ageing and Cognitive Epidemiology (cross-council funded).

Prof Holmes has been an investigator/co-investigator on research grants totalling ~£10.1M. She has published 101 original research papers and review articles (collectively attracting more than 14k citations), in addition to 14 book chapters and has presented her group's research at numerous scientific conferences both nationally and internationally. She has supervised/co-supervised 19 PhD students, 11 MSc students and acted as external examiner in close to 40 occasions.

What professional and personal reflection would you like to offer on your time at the University of Edinburgh?

Having studied Physiology and Neuroendocrinology, which involves a whole body research approach and understanding that covers many disciplines, I was delighted to find a strong collaborative sprit within the University of Edinburgh. I was introduced to molecular biology and the development of transgenic models to delve deeper into the molecular mechanisms underpinning the consequences of stress at different stages of life. Back at the whole animal level, I was able to collaborate with imaging experts to study the effects of stress on brain structure and function in adults, as well as placental function in utero. This led to my taking on the role of Director of Edinburgh Preclinical Imaging (EPI) to provide in vivo imaging of small animals across the University.

I consider good mentoring of young researchers is crucial for them to take advantage of the opportunities for career progression. I received tremendous support and advice from my mentor throughout my career and in turn I have acted as a mentor within my research centre and University -wide mentoring schemes.

Finally, working in the relatively small research field of Neuroendocrinology, I consider it important to support other Neuroendocrinologists. I have been a member of the British Society for Neuroendocrinology (BSN) from its early conception as the British Neuroendocrine Group, until the present day. I served on the steering committee for 10 years and was their treasurer for 8 years to distribute money from the BSN journal to support neuroendocrinology research. I remain a senior editor of the BSN’s journal, Journal of Neuroendocrinology.

Key research publications

Edinburgh Imaging would like to thank Professor Megan Holmes for her work and contributions to the University and Edinburgh Imaging over the years, and wish her a happy and healthy retirement.

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