Dr Scott Mackenzie
- Lecturer (Institute of Cardiovascular & Medical Sciences)
- Associate (School of Medicine, Dentistry & Nursing)
My core research investigates the cardiovascular impact of the steroid hormones aldosterone and cortisol, particularly the regulation of their production by the adrenal gland. Loss of this tightly-controlled process has severe consequences for the vascular system, including hypertension, and to damage of organs including the heart and kidneys. Much of my work has focused on how common genetic variations leads to overproduction of these steroids, predisposing large sections of the population to high blood pressure, which often goes undiagnosed and untreated, despite the availability of effective treatments. To this end, I have contributed to several large-scale genetic studies identifying polymorphisms at steroidogenic loci that could aid diagnosis and therapeutic targeting of specific subtypes of hypertension. My work also includes investigation of the mechanisms by which these polymorphisms exert their effects, including studies of transcriptional activity, promoter binding, mRNA quantification and microRNA regulation. I am currently developing an interest in stress and its impact on cardiovascular disease through aldosterone secretion.
My research has a truly translational approach, encompassing laboratory analysis of isolated cells, investigation of tissue samples and full clinical studies. As an example of the latter, I am currently involved in the Europe-wide ENS@T-HT study, which is using ‘omics’ approaches to develop diagnostic signatures for various endocrine forms of hypertension. To this end, I am involved in analysing levels of circulating microRNAs in hypertensive patients recruited in Glasgow and throughout Europe. As well as developing improved procedures to more effectively diagnose patients with such conditions as Primary Aldosteronism or Cushing’s Disease, it is highly likely that this project will yield mechanistic insights into the regulation and action of aldosterone and cortisol in health and disease.
I have productive research projects with numerous colleagues within the University of Glasgow, while my past and present external collaborators include Professor John Connell at the University of Dundee, Dr Trevor Bushell at Strathclyde University, Professor Maria-Christina Zennaro at INSERM, Paris and Professor William Rainey at the University of Mississippi. I have received research funding from the European Union, the Chief Scientist Office and the British Heart Foundation and I am a former RCUK and Hypertension Trust Research Fellow. Such funding has enabled my colleagues, students and me to maintain an active record of publishing in prominent journals such as Circulation, Nature and Hypertension over the last 20 years.
I am active in various professional consortia and societies, including the Society for Endocrinology, where I have been a longstanding member elected to its Science Committee, co-convenor of its Adrenal and Cardiovascular Network and leader of its Career Development Workshop, which is the Society’s main initiative for promoting the early career researchers among its over 2,600 members. I am a reviewer for funding bodies including the Medical Research Council and British Heart Foundation, and for journals including Endocrinology, Clinical Endocrinology and Hypertension.
Our group’s core research investigates the production of the steroid hormones aldosterone and cortisol by the cortex of the adrenal gland. In particular, we wish to understand how genetic variation between individuals influences the regulation of these steroids’ production and how this results in high blood pressure. To this end, I have contributed to several large-scale genetic studies involving our main genes of interest, aldosterone synthase and 11β-hydroxylase. I am currently investigating whether polymorphisms in the 11β-hydroxylase gene result in its reduced expression.
As well as contributing to our group’s core studies of adrenocortical steroid production, many of my studies have examined the emerging area of extra-adrenal steroidogenesis, whereby tissues such as the brain and adipose tissue appear capable of producing low levels of aldosterone and cortisol. I have detected the aldosterone synthase and 11β-hydroxylase enzymes within brain tissue and demonstrated that their genes can be regulated within the brain independently of the adrenal gland. Current studies are investigating a link between cortisol production within the brain and Alzheimer’s disease. Other ongoing research includes the study of these genes’ production within heart tissue and fat tissue, in an attempt to better understand the processes underlying heart disease and obesity.
I have productive research projects with a number of national and international collaborators, including Dr Trevor Bushell at Strathclyde University, Professor Jonathan Seckl at Edinburgh University and Professor Celso Gomez-Sanchez at the University of Mississippi.
- Corticosteroid Production
Grants and Awards listed are those received whilst working with the University of Glasgow.
2015 - 2020
- Understanding the genetic regulation of adrenal steroid hormones in cardiovascular disease - Developing a stratified approach to cardiovascular care
Chief Scientist Office
2014 - 2016
- Identification and characterization of CYP11B1 alternative isoforms in human adrenals and H295R cells.
2011 - 2013
- Regulation of aldosterone synthase (CYP11B2) and 11b-Hydroxylase gene expression by novel micro RNAs
British Heart Foundation
2010 - 2013
- Research Councils UK academic fellowships - adrenal and extra-adrenal production of corticosteroids
Engineering and Physical Sciences Research Council
2006 - 2011
- Functional analysis of polymorphisms/mutations in steroidogenic genes and their implications for human cardiovascular homeostasis
British Heart Foundation
2005 - 2007
- The role of corticosteroids in obesity
2004 - 2006
- Quantification of 11 beta-hydroxylase (CYP11B1) gene expression in adipose tissue from normal and obese human subjects
2004 - 2005
- Expression of 11 beta-hydroxylase and aldosterone synthase in the human central nervous system
North Glasgow University Hospitals NHS Trust
2003 - 2005
- Identification and analysis of mutations in steriodogenic genes and their functional implications of human cardivacular homestasis
British Heart Foundation
2003 - 2005
- 2005 - 2010: Research Councils UK Academic Fellowship
- 2004 - 2006: Hypertension Trust Research Fellow