Mark Nixon, PhD
Lecturer &
Principal Investigator
Email: M.Nixon@ed.ac.uk
Phone: +44 131242 6292
Accepting PhD Students
Research Area
Glucocorticoids are critical stress hormones that regulate a number of physiological processes including fuel metabolism and immune modulation. Conditions of overt glucocorticoid excess such as Cushing’s disease or chronic glucocorticoid treatment are associated with significant cardiometabolic abnormalities, including obesity, hyperglycemia, and hypertension. Indeed, while glucocorticoid treatment is a cornerstone in the management of many inflammatory diseases, and glucocorticoid replacement is essential for survival in patients with various forms of adrenal insufficiency, cardiovascular disease risk is increased 6-fold in people exposed to long-term supraphysiological doses of glucocorticoids. Notably, this association is more pronounced in women, highlighting sexually dimorphic responses to glucocorticoid therapy.
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​Obesity, as a key driver of cardiovascular risk, is associated with complex glucocorticoid dysregulation, the direction of causality and the pathophysiological consequences of which are unknown. My lab addresses the hypothesis that obesity-induced glucocorticoid dysregulation is a key component in the development of these significant co-morbidities. Similarly, cardiovascular risk is increased in those subjects exposed to glucocorticoid excess. My lab’s discovery of mechanisms which confer tissue-specific control of glucocorticoid action independently of circulating levels provide the basis for a paradigm shift in the understanding of glucocorticoid biology, and uniquely position us to determine the impact of these mechanisms on co-morbidities associated with obesity, as well as on glucocorticoid-induced cardiovascular risk.
Funding
Profile
My lab harnesses the power of pre-clinical models of obesity and glucocorticoid-induced cardiometabolic dysregulation, together with translational approaches in humans, to better understand the underlying pathologies of cardiometabolic complications and to seek out better therapeutic approaches. Our lab has a specific interest type 2 diabetes, hypertension, atherosclerosis, and cardiac remodelling.
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I obtained my undergraduate degree in Immunology from the University of Edinburgh, including a placement in the lab of Prof Ian Dransfield in the Centre for Inflammation Research, before undertaking a PhD at the Centre for Cardiovascular Science with Prof Ruth Andrew examining the role of glucocorticoid metabolism on inflammation. In 2012, I moved to the Integrative Biology and Pharmacology Department at the University of Texas Health Science Center Houston to continue my Postdoctoral training with Prof Rebecca Berdeaux. Here I identified a novel role for the AMPK-related kinase SIK1 in regulating glucose homeostasis in obesity.
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In 2014, I joined Prof Brian Walker’s group at the Centre for Cardiovascular Science in Edinburgh and demonstrated a novel role for the transmembrane exporter ABCC1 in regulating adipose tissue glucocorticoid exposure. In 2018, I was awarded a BHF Basic Science Intermediate Research Fellowship to establish my own group in Edinburgh investigating the contribution of corticosteroid binding globulin (CBG) cleavage to adipose glucocorticoid delivery in obesity.
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Mentors
Prof Ian Dransfield
Prof Ruth Andrew
Prof Rebecca Berdeaux
Prof Brian Walker
The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure
Luke D Boyle, Allende Miguelez-Crespo, Mhairi Paul, Elisa Villalobos, Julia NC Toews, Lisa Ivatt, Boglarka Nagy, Marisa Magennis, Natalie ZM Homer, Ruth Andrew, Victor Viau, Geoffrey L Hammond, Roland H Stimson, Brian R Walker & Mark Nixon.
Nat Communications. 2025 Jan 09.
PMID: 39788946
Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia
Catriona J Kyle, Luke D Boyle, Mark Nixon, Natalie ZM Homer, Joanna P Simpson, Alison Rutter, Lynne E Ramage, Alex Kelman, Ellen M Freel, Ruth Andrew, Brian R Walker, Roland H Stimson.
Eur J Endocrinol. 2024 Nov 27;191(6):535-544
PMID: 39546623
ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet
Elisa Villalobos, Allende Miguelez-Crespo , Ruth A Morgan , Lisa Ivatt, Mhairi Paul, Joanna P Simpson, Natalie ZM Homer, Dominic Kurian, Judit Aguilar, Rachel Kline, T Wishart, Nicholas Morton, Roland H Stimson, Ruth Andrew, Brian R Walker, Mark Nixon.
J Endocrinol. 2024 Jun 1:JOE-24-0024.
PMID: 38829241
High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice.
Costello HM, Krilis G, Grenier C, Severs D, Czopek A, Ivy JR, Nixon M, Holmes MC, Livingstone DEW, Hoorn EJ, Dhaun N, Bailey MA.
Cardiovasc Res. 2023 Jul 6;119(8):1740-1750.
PMID: 36368681