Mark Nixon
BHF Research Fellow
Address
- Street
-
Queen's Medical Research Institute
Edinburgh Bioquarter
47 Little France Crescent - City
- Edinburgh
- Post code
- EH16 4TJ
Undergraduate teaching
Course Instructor: Endocrine Physiology and Pharmacology (Hons)
Course Instructor: Pharmacology (Hons)
Board of Examiners: Pharmacology (Hons)
Postgraduate teaching
Couse Contributor: MSc by Cardiovascular Research
Open to PhD supervision enquiries?
Yes
Current PhD students supervised
Lisa Ivatt (BHF PhD Studentship): 2020-2024
Clare Macleod (BHF PhD Studentship): 2020-2024
Past PhD students supervised
Luke Boyle (Clinical PhD Fellow): 2016-2023
Current research interests
Glucocorticoid excess in adipose tissue drives increased cardiovascular disease risk, including visceral obesity, hyperglycemia and hypertension. Thus, limiting glucocorticoid action in adipose tissue may reduce cardiovascular disease. My overarching research goal is to understand the physiological and pathophysiological mechanisms controlling adipose tissue glucocorticoid exposure. In particular, my group has undertaken studies to assess the impact of the neutrophil elastase (NE), corticosteroid binding globulin (CBG), glucocorticoid axis on adipose physiology. Plasma CBG binds glucocorticoids with high affinity and controls their plasma distribution and metabolic clearance. In humans, ~85% of circulating cortisol is bound by CBG, ~10% is bound to albumin, leaving only ~5% freely accessible to target tissues. Thus, changes in CBG levels or binding affinity alters the availability of biologically active glucocorticoids. My research combines pre-clinical murine models of obesity, insulin resistance, vascular dysfunction and atherosclerosis, with translational in vitro studies utilising primary human cells and collaborative clinical studies. Paired with distinct genetic and methodological tools, this provides my lab with a unique ability to functionally evaluate pathways hypothesised to regulate glucocorticoid biology, determine their importance in driving cardiovascular disease risk, directly translate those findings into human physiology, and ultimately identify more clinically effective targets for therapy development.Knowledge exchange
I have established an international network of collaborators to support my research, including:
External:
- Prof Geoff Hammond and Prof Victor Viau (University of British Columbia, Canada).
- Prof Onno Meijer and Dr Jan Kroon (Leiden University, Netherlands).
- Prof Mauro Giacci (King’s College London).
- Dr David Severs (Erasmus MC, Netherlands).
- Dr Ingrid Gelissen (University of Sydney, Australia).
- Dr Marie-Pierre Moisan (University of Bordeaux, France).
- Dr Shuji Sai (Hohhaido University, Japan).
- Dr Li Kang (University of Dundee).
- Dr Ruth Morgan (SRUK).
Internal :
- Prof Matt Bailey (CVS).
- Prof Paddy Hadoke (CVS).
- Prof Ruth Andrew (CVS).
- Prof Rebecca Reynolds (CVS).
- Prof Rob Semple (CVS).
- Prof Roland Stimson (CVS).
- Dr Cecile Benezech (CVS).
- Dr Doug Gibson (CIR).
- Orwa Falah (Vascular Surgeon, RIE)
- Euan McGregor (Consultant Vascular Anaesthetist, RIE)
Current project grants
University of Edinburgh/University of Copenhagen Seed Funding: 2023-2024
BHF Project Grant: 2023-2025
BHF Basic Science Intermediate Research Fellow: 2018-2023
BHF PhD 4-Yr Studentship: 2020-2024
BHF PhD 4-Yr Studentship: 2020-2024
Past project grants
Bioscientifica COVID Response Award: 2020-2021
Society for Endocrinology Early Career Grant: 2011-2012
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High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
In:
Cardiovascular Research
DOI: https://doi.org/10.1093/cvr/cvac160
Research output: Contribution to Journal › Article (E-pub ahead of print) -
The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action
In:
Nature reviews endocrinology
DOI: https://doi.org/10.1038/s41574-022-00745-9
Research output: Contribution to Journal › Article (E-pub ahead of print) -
ABCC1 modulates negative feedback control of the hypothalamic-pituitary-adrenal axis in vivo in humans
In:
Metabolism, vol. 128
DOI: https://doi.org/10.1016/j.metabol.2021.155118
Research output: Contribution to Journal › Article (Published) -
Glucocorticoids: Fuelling the Fire of Atherosclerosis or Therapeutic Extinguishers?
In:
International Journal of Molecular Sciences, vol. 22, pp. 7622
DOI: https://doi.org/10.3390/ijms22147622
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice.
In:
Molecular Metabolism
DOI: https://doi.org/10.1016/j.molmet.2021.101225
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Effects of Obesity And Insulin on Tissue-Specific Recycling Between Cortisol And Cortisone in Men
In:
The Journal of Clinical Endocrinology & Metabolism (JCEM)
DOI: https://doi.org/10.1210/clinem/dgaa896
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants
In:
Immunity, vol. 52, pp. 700-715.e6
DOI: https://doi.org/10.1016/j.immuni.2020.03.011
Research output: Contribution to Journal › Article (Published) -
Quantitative analysis of 11-dehydrocorticosterone and corticosterone for preclinical studies by liquid chromatography triple quadrupole mass spectrometry
In:
Rapid communications in mass spectrometry
DOI: https://doi.org/10.1002/rcm.8610
Research output: Contribution to Journal › Article (Published) -
Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta
In:
AJP - Endocrinology and Metabolism, vol. 317, pp. E109-E120
DOI: https://doi.org/10.1152/ajpendo.00551.2018
Research output: Contribution to Journal › Article (Published) -
Role of hepatic glucocorticoid receptor in metabolism in models of 5αR1 Deficiency in Male Mice
In:
Endocrinology
DOI: https://doi.org/10.1210/en.2019-00236
Research output: Contribution to Journal › Article (Published) -
Androgens modulate glucocorticoid receptor activity in adipose tissue and liver
In:
Journal of Endocrinology, vol. 240, pp. 51-63
DOI: https://doi.org/10.1530/JOE-18-0503
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Dysregulation of cortisol metabolism in equine pituitary pars intermedia dysfunction
(10 pages)
In:
Endocrinology, vol. 159, pp. 3791–3800
DOI: https://doi.org/10.1210/en.2018-00726
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
In:
Scientific Reports, vol. 7
DOI: https://doi.org/10.1038/s41598-017-10410-1
Research output: Contribution to Journal › Article (Published) -
ABCC1 confers tissue-specific sensitivity to cortisol versus corticosterone: a rationale for safer glucocorticoid replacement therapy
(12 pages)
In:
Science Translational Medicine, vol. 8
DOI: https://doi.org/10.1126/scitranslmed.aaf9074
Research output: Contribution to Journal › Article (Published) -
Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation
(12 pages)
In:
Cell Metabolism, vol. 24, pp. 130-141
DOI: https://doi.org/10.1016/j.cmet.2016.06.011
Research output: Contribution to Journal › Article (Published) -
Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity
(13 pages)
In:
Molecular Metabolism, vol. 5, pp. 34-46
DOI: https://doi.org/10.1016/j.molmet.2015.10.004
Research output: Contribution to Journal › Article (Published) -
When two glucocorticoids are better than one: 'Relative corticosterone deficiency' in human metabolic syndrome
(1 page)
In:
Psychoneuroendocrinology, vol. 61, pp. 29-29
DOI: https://doi.org/10.1016/j.psyneuen.2015.07.469
Research output: Contribution to Journal › Meeting abstract (Published) -
Salicylate Downregulates 11β-HSD1 Expression in Adipose Tissue in Obese Mice and in Humans, Mediating Insulin Sensitization
(7 pages)
In:
Diabetes, vol. 61, pp. 790-796
DOI: https://doi.org/10.2337/db11-0931
Research output: Contribution to Journal › Article (Published) -
5α-Reduced glucocorticoids: a story of natural selection
(17 pages)
In:
Journal of Endocrinology, vol. 212, pp. 111-127
DOI: https://doi.org/10.1530/JOE-11-0318
Research output: Contribution to Journal › Article (Published) -
It takes two to tango: Dimerisation of glucocorticoid receptor and its anti-inflammatory functions
(10 pages)
In:
Steroids, vol. 78, pp. 59-68
DOI: https://doi.org/10.1016/j.steroids.2012.09.013
Research output: Contribution to Journal › Article (Published)
Conference details
Keystone Symposia (Drivers of diabetes), Palm Springs, May 2023
American Physiology Summit, Long Beach, April 2023
British Endocrine Society, Harrogate, November 2022
Organiser
Adipose Tissue Discussion Group, Edinburgh, March 2023