Scott MacKenzie is a lecturer at the Institute of Cardiovascular and Medical Sciences at the University of Glasgow. Dr MacKenzie’s research focuses on adrenocortical production of the steroid hormones, aldosterone and cortisol, and investigates how genetic variability can affects their involvement in causing high blood pressure. In this interview, he tells us more about his research, career path and his role as an Adrenal and Cardiovascular Network convenor.
What inspired you into endocrinology, and why adrenocortical research in particular?
I got into endocrine research by chance. I was studying for an undergraduate degree in genetics at the University of Glasgow in the mid-90s and a lecturer happened to mention that any students interested in a summer research project should go and see John Connell. Everything came from that. Professor Connell, alongside Robert Fraser and Eleanor Davies, was particularly interested in aldosterone secretion by the adrenal gland and the genes that regulated it. At that time, there was also emerging evidence that other tissues including the brain were making aldosterone, so I was set to work on that through a Society for Endocrinology Summer Studentship. Unfortunately, the 8-week project went extremely smoothly, generating some nice data and giving me completely unrealistic expectations of scientific research! On the basis of this, I was then offered a PhD project in the same lab devoted to investigating extra-adrenal production of aldosterone in the rodent brain. I continued researching in this area, but over the years, I came to the conclusion that extra-adrenal production of aldosterone is unlikely to be of any physiological importance in humans. Fortunately, new questions were starting to be asked around adrenal secretion of aldosterone and I was able to apply the methods I had developed to that area. Now I am involved in projects that cover several aspects of this, with particular interest in how secretion can become dysregulated or excessive, as in primary aldosteronism (PA).
Tell us a little more about your current research?
I’m currently involved in various projects examining aspects of aldosterone secretion, which I think is an interesting and important field of endocrinology that has an impact on the cardiovascular health of large sections of the population. My current work includes aldosterone regulation by microRNA, analysis of common genetic polymorphisms that might predispose large sections of the population to PA (and therefore hypertension), and the identification of circulating biomarkers that might aid in the earlier and more accurate diagnosis of different forms of endocrine hypertension. The things I tend to be most proud of are the little bits of problem solving that arise in the course of lab work. I was quite pleased with a slightly obscure method I developed to confirm the unequal expression of two different forms of the highly similar CYP11B1 and CYP11B2 genes.
What do you think will be the next big or important breakthrough in adrenocortical research?
The discovery that the majority of aldosterone-producing adenomas contain mutations at one of just a few key genes encoding ion channels was really a big breakthrough that advanced our understanding of the pathophysiology underlying the majority of PA cases. At the same time, improvements in diagnostic testing for PA are revealing it to be far more common than we had previously thought. I think this will lead to a redefinition of PA to some extent, as we identify mechanisms that result in aldosterone hypersecretion under certain environmental circumstances or in certain sections of the population who are genetically predisposed to respond in this manner. Ultimately, this could result in better diagnosis and more targeted treatment for endocrine-related hypertension.
I’m currently very interested in the impact of environmental and physical stress on aldosterone secretion. The hypothalamic-pituitary-adrenal axis has long been thought to regulate aldosterone secretion in a very limited manner, but recent clinical studies suggest a sizeable minority of hypertensive individuals react to stress by producing high levels of aldosterone. Understanding what predisposes these people to respond in this manner is, I believe, of great importance and could have major implications for how we react to stressful situations in everyday life and its impact on our cardiovascular health.
What do you think are the biggest challenges faced by academic research?
I think the greatest challenge in current scientific research doesn’t apply to any one field but to us all. That is how we ensure that young researchers coming through – particularly basic scientists – have a viable and stable career structure that enables them to progress and thrive in an academic environment. A lot of time, money and training is being invested in these people, but too many are being lost to science as they become disenchanted by successive short-term contracts and the uncertainty surrounding a career in scientific research. I think it is incumbent on older scientists to recognise just how much the career prospects and funding structures have altered in recent years, and to use whatever influence we have to push for greater early career support at institutional and national levels.
Are there any controversies in your research area? How do you think they will be resolved?
There are certainly controversial areas in my field; some may argue with my opinion that extra-adrenal aldosterone production in humans is of no importance. Others (if the comments on my recent grant proposal are anything to go by) will disagree with my assertion that stress is an important factor in aldosterone secretion. But, ultimately, any scientific disputes will be resolved as they have always been: by well-designed and well-executed experimental study.
What do you enjoy about being an Endocrine Network convenor, and how do you think it may benefit others?
I think that Endocrine Networks have tremendous potential to provide opportunities for researchers, particularly those in their early careers, by enabling them to gain supportive and informed advice from more senior members. I hope we are able to build a vibrant online community that is complemented by ‘real-life’ meetings, such as the Research Incubators at the SfE BES 2017 conference, which proved an excellent forum for researchers to get feedback on projects under development. Ultimately, the success of these initiatives depends on its participants, so I would urge all members in relevant areas of research to sign up to a network and get involved.
Do you have any words of wisdom for aspiring endocrinology researchers?
Although I think opportunities are harder to come by now than they were in ‘my day’, young researchers can still distinguish themselves from their peers in the same ways. That means taking every opportunity to make themselves known to prospective employers and supervisors (the dreaded ‘networking’) while at the same time not being too discouraged by the high number of rejections that almost inevitably follow. It also means exploiting opportunities that organisations like the Society for Endocrinology make available to them, such as Travel Grants, Early Career Grants and Career Development Workshops. Applying for these or getting involved with the Networks or the Early Career Steering Group can be an excellent way to develop your research and get your name known in endocrine circles.
The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.