Meet the Endocrinologist: Dr Scott MacKenzie, expert in adrenocortical biology

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.

To join an Endocrine Network login to the ‘My profile’ section of the Members’ Area and select ’Endocrine Networks’.

Meet the Endocrinologist: Professor Franks, expert in reproductive biology and medicine

Stephen Franks is Professor of Reproductive Endocrinology at Imperial College Faculty of Medicine and Consultant Endocrinologist at St Mary’s and Hammersmith Hospitals, London. Prof Franks’ clinical and laboratory research focuses on the hypothalamic-pituitary-ovarian axis, with a particular interest in polycystic ovary syndrome. In this interview, he tells us more about his research, current challenges in reproductive endocrinology and his role as a Reproductive Endocrinology and Biology Network convenor.

What inspired your passion for endocrinology, and reproductive endocrinology in particular?

As a young medical registrar with no experience of research, I was offered a research fellowship to study the physiology and pathology of prolactin (my supervisor and mentor was Howard Jacobs whose enthusiasm was contagious). It was an exciting time for prolactin research because measuring prolactin in blood was new. Radioimmunoassays for prolactin were problematic and I had to set one up from scratch that enabled us to show that hyperprolactinaemia was a common cause of amenorrhoea. The project got me hooked on endocrinology, and reproductive endocrinology in particular, so I carried on to train in internal medicine and endocrinology before finding the ideal clinical academic staff position, which I have held ever since.

Tell us a little more about your current position and work?

As Professor of Reproductive Endocrinology, my clinical practice focuses on reproductive endocrine problems with strong collaboration among my gynaecological colleagues. My main research goals for the last 30 years have focused on trying to unravel the complexities of both reproductive and metabolic problems of polycystic ovary syndrome (PCOS). This has involved clinic-based studies, epidemiological studies and lab-based studies, using human ovarian cells and animal models. My lab-based studies are jointly led with my colleague Professor Kate Hardy, a reproductive biologist.

Over the last decade, what do you think have been the most significant advances in reproductive endocrinology research or clinical practice?

There are many, including the discovery of the importance of the neuroendocrine signalling relay that impacts on gonadotropin secretion, notably the role of kisspeptin, neurokinin and dynorphin neurones. In the area of PCOS research, new data emerging from genome-wide association studies have given us clues to the genetic basis of this complex endocrine disorder.

What do you think has been the most surprising discovery in the field over the last decade?

Discovery, in the mouse at least, that anti-Mullerian hormone (AMH) has receptors in hypothalamic neurones, and can affect secretion of gonadotropin-releasing hormone (GnRH). For many years, it was thought that AMH was simply a local hormone, produced by the Sertoli cells of the testis, that played a key part in differentiation of the male reproductive tract. However, much more recently, AMH was also found to be synthesized and secreted by granulosa cells of the ovary, and has since been widely used as a clinical marker of ovarian follicular reserve. So, the report, by Dr Paolo Giacobini and colleagues in Lille, that this hormone has specific receptors in the mouse hypothalamus and that AMH has a profound effect on GnRH secretory activity was, to say the least, unexpected. The relevance of these findings to human physiology remains to be seen but perhaps we should not be too surprised, given that related gonadal growth factors, such as inhibins and activins, also have actions on the hypothalamic-pituitary axis.

What clinical advances do you think could make a difference for patients affected by reproductive health conditions in the near future?

I would hope that understanding more about the genetic basis of PCOS, particularly differences in genotype between individuals, will lead to more specific and effective ways of treating PCOS, rather than (the nevertheless important) management of symptoms.

What do you think are the main challenges faced by your clinical specialty?

There is a shortage of endocrinologists with a special interest in reproductive endocrinology. This is partly because not all endocrine training programmes offer sufficient experience of this sub-specialty.

Are there any major controversies in your practice area?

One good example is whether PCOS is a risk factor for cardiovascular events. Women with PCOS have risk markers for cardiovascular disease but do they actually have more heart attacks? We lack long-term, longitudinal studies on this, and therefore it would be wise to consider appropriate screening for cardiovascular risk factors in women with PCOS (including cholesterol, lipid and lipoprotein measurements), especially if they are obese. Despite the lack of definitive information about cardiovascular events in women with PCOS, it seems sensible to advise women with PCOS about the importance of diet and exercise to reduce the risk of cardiovascular disease.

What is the most unusual part of your work?

As a reproductive endocrinologist, much of my work and research centres around problems related to reproductive health and ovarian disorders. That naturally means that I have close links with my gynaecological colleagues and, for example, we ran a joint infertility clinic, albeit with a focus on induction of ovulation. Much of my research is laboratory based and, in that area, my long-term collaboration with my reproductive scientist colleague, Professor Kate Hardy, plays an important part. We jointly run our research group and the interaction between clinical and basic scientists is an important aspect in both research and training.

What do you enjoy about being a Reproductive Endocrinology and Biology Endocrine Network convenor, and how do you think the Network can benefit others?

The network facilitates interdisciplinary research through meetings in reproductive endocrinology and biology, using joint sponsorship from the Society for Endocrinology and the Society for Reproduction & Fertility (SRF), by providing a platform for collaborative research. Andy Childs and I (together with Kate Hardy) are currently putting together a programme of international speakers for a meeting on growth factor signaling in the ovary, to which the Society has contributed a meeting grant. An important feature of our Network is that it also involves input (both intellectual and financial) from the SRF, and we shall also be seeking involvement from them. Also, in planning, is another meeting of ReproSouth (again, jointly with SRF), an informal event where students and post-docs (from the Midlands and Wales, as well as London and the South) are encouraged to present work in progress (scheduled for June, this year). Ahead of our next Network meeting at SfE BES 2018 in November we will be canvassing topics for collaborative research across centres in the UK.

Further details on the ReproSouth meetings can be obtained from Stephen Franks and Andy Childs directly.

Do you have any words of wisdom for young endocrinologists out there?

Whether you are planning a career in academic endocrinology, clinical practice or related pathways, there is no substitute for the experience and excitement of being involved in a research project. My own experience of being introduced to research as a very junior physician is that it opened up a completely new way of thinking. So, whether you stay in research or not, it allows you to approach problems in a unique way. And, despite the trials and tribulations, the rewards of a career in academic endocrinology are many, including the privilege of being part of a national and international “family” of colleagues and friends.

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.

To join an Endocrine Network login to the ‘My profile’ section of the Members’ Area and select ’Endocrine Networks’.

 

 

Meet the Endocrinologist: Professor Thakker, endocrine neoplasia expert

Professor Rajesh Thakker, Fellow of the Royal Society and May Professor of Medicine at the University of Oxford, specializes in Multiple Endocrine Neoplasia 1 (MEN1) and neuroendocrine tumours (NETs). He tells us more about his career inspirations, advances, challenges and opportunities within the field, both in clinical research and practice, and how his role as Endocrine Neoplasia Syndromes Network Convenor supports his work. 

What inspired you into endocrinology, and why did you then focus on neuroendocrine tumour research?

This began with a patient, as is often the case for physician-scientists. Whilst studying Natural Sciences at Cambridge, I developed an early interest in endocrinology. Later, as a registrar at The Middlesex Hospital in London, I was admitting a young woman, from A&E, with severe hematemesis due to a peptic ulcer. She also had a history of renal stones due to primary hyperparathyroidism; and further investigation showed she had a prolactinoma. All this indicated that she had multiple endocrine neoplasia type 1 (MEN1), a genetic disorder inherited as an autosomal dominant trait.

At the time, the genetic defect and the underlying molecular and cellular mechanisms causing MEN1 were unknown. Fortunately, I was then working with Jeffrey O’Riordan, who had expertise in endocrinology and calcium homeostasis, and who encouraged me to pursue research. Moreover, looking after patients with endocrine disorders led me to realise two things. First, that there were still many gaps in our knowledge of the underlying mechanisms of endocrine conditions; and second, that these mechanisms could be elucidated through the recent advances in molecular biology.

This was exemplified by an inspiring lecture, by Jack Martin, on the identification of parathyroid hormone-related peptide (PTHrP), as the humoral factor causing the hypercalcemia of malignancy. During the lecture, he illustrated the usefulness of the molecular approach to understanding fundamental disease processes. Deeply excited by this discovery and its scientific approach, I put my efforts into obtaining a Medical Research Council (MRC) clinical training fellowship, to further the understanding of the biological mechanisms involved in endocrine disorders.  Since then, as a physician-scientist, I have been engaged in the investigation of the molecular genetics of endocrine diseases – a constant source of challenge and excitement in uncovering the underlying biological mechanisms that cause human disease.

Can you tell us a little about your current research and clinical work? 

My current research focuses on two main areas. The first is to identify genes whose mutations are involved in causing endocrine tumours and diseases – and area where the advances of next generation sequencing have tremendously helped, and where there is enormous potential to make new discoveries and translate them for patient benefit. The second area explores the mechanisms of G-protein coupled receptor (GPCR) signaling – we have recently identified a non-canonical pathway in which signaling by the calcium-sensing receptor (a GPCR) involves endosomes. Targeting this non-canonical endosomal pathway may elucidate novel signaling targets that could be altered by pharmacological compounds.

Over the last decade or so, what do you think have been the most significant advances in neuroendocrine tumour clinical practice, and/or research?

The implementation of genetic testing has been very useful – it had a major impact in the diagnosis and management of patients with endocrine tumour syndromes, such as multiple endocrine neoplasia. Screening for these tumours, including neuroendocrine tumours, results in their earlier detection and treatment. On the research front, the introduction of many new treatments, e.g. tyrosine kinase inhibitors and mTOR inhibitors, as well as some emerging therapies such as epigenetic modifiers and gene therapy, which are in the pre-clinical stages, have been very significant.

What do you think will be the next big or important breakthrough for treatment or diagnosis of neoplasia syndromes?

The next big breakthrough for diagnosis is likely to be the advent of enhanced imaging modalities that will detect the tumours at an early stage, together with molecular biomarkers that will help their detection and monitoring. When it comes to treatments, the next big step is likely to involve emerging compounds such as monoclonal antibodies, agents targeting oncogenic pathways, radionuclide therapy and epigenetic modifiers.

What do you think are the biggest challenges faced by your clinical specialty?

The biggest challenges faced by our clinical specialty, and indeed all clinical specialties, are the difficulties in the training programmes of our younger doctors. Morale amongst the young doctors is low, and they feel undervalued. This is totally counterproductive, as we attract the brightest and most talented students into medicine, and yet the current organizational infrastructure and systems seem to thwart their talents and abilities rather than allowing them to thrive and expand and achieve their aspirations.  These difficulties are due to multiple factors that include:

  • lack of flexibility in training pathways;
  • the rotas, which are often not provided well in advance and are rigid such that forward planning for leave is precluded, and have gaps that result in increased workload for the doctors and a strain in the provision of service;
  • the absence of a clinical firm with senior doctors (consultants) that provide role models, inspiration and encouragement for the younger generation to aim high, and to support them in their careers.

All of this has resulted in diminished attractiveness for the role of the “medical registrar”, with a decrease in recruitment of top caliber doctors. We need to act fast to rectify the current situation if we are going to maintain the high excellence of our medical practice and its vital underpinning by scientific advances. To achieve this, all the learned societies and NHS need to work with the Royal Colleges to deliver on the recommendations made by the report “The medical registrar: Empowering the unsung heroes of patient care” (The Royal College of Physicians, March 2013), and thereby improve the situation for our younger doctors.

Are there any controversies in your practice area? How do you think they will be resolved?

There are many controversies in the diagnosis and management of NETs, which largely stem from a lack of adequate clinical trials that would provide evidence of their efficacy – thus, we are reliant on expert opinions that aren’t always in agreement. In rare diseases such as NETs, it would be important for experts from multiple centres to collaborate, designing studies to evaluate the methods used for diagnosis and treatments, so that the most effective tests and treatments can be implemented in a standardised manner for our patients.

What do you enjoy about being an Endocrine Neoplasia Syndromes Network convenor, and how do you think it may benefit others?

It is a privilege to work with enthusiastic colleagues at different career stages, and to have a free exchange of ideas between scientists, clinician-scientists and clinicians, all of whom have a “can-do” approach.  As a convenor, I have learned a lot from my colleagues and patients – the free debate that we have helps to advance the field and provide insights into the biology of the disorders, and to explore ways of benefiting our patients.

Do you have any words of wisdom for the younger generations of endocrinologists?

Endocrinology is a fascinating discipline – it will satisfy those who are intellectually curious, yet are equally keen to apply their knowledge to a practical setting.  Moreover, endocrinology embraces a diverse spectrum of biological and metabolic processes, whose dysregulation affects virtually every human disorder.  Furthermore, in the UK we have major international leaders in endocrinology, and there are ample and extraordinary opportunities for young endocrinologists to get top training in clinical endocrinology and basic science. Finally, we have outstanding funding organisations such as the Medical Research Council and the Wellcome Trust, which have an excellent track record in funding research in endocrinology.

Young endocrinologists can have a wonderful future in this discipline. My advice to aspiring endocrinologists would be to not ask what endocrinology can do for you, but to instead ask what you can do for endocrinology – you will then be assured of an exciting and satisfying career.

 

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.

To join an Endocrine Network login to the ‘My profile’ section of the ‘Members’ Area and select Endocrine Networks.

The conference that stirred my scientific passions (and got me a cool mug!)

What to expect from SfE BES as an Early Career researcher / medical trainee

Scientific conferences are not just an unparalleled opportunity to dive deeper into what’s going on in your specialty. Much more importantly, they are where the little things – the random encounters, the unexpected conversations that can lead to career turning points happen. Do you remember, or can you imagine, the nervous expectation, the excitement -perhaps a tinge of bewilderment- of being there for the first time?

Matthew Sinton, PhD student in Cardiovascular Science at the University of Edinburgh attended his first ever scientific conference, SfE BES, in November 2017. Read how the experience saw him equipped with a sense of purpose, and a taster of what the endocrinology community can do for his career (and could do for yours too, if you’re an SfE BES newbie!).

Amongst the multitude of questions whirling around in my head when I started my PhD, there was one I never realised would be so important: which societies should I join? The first one recommended by my supervisor was the Society for Endocrinology, so I did my due diligence – I found out what the role of the Society was, and how it could support me throughout my PhD and my career beyond.

One of the first opportunities that I came across was the Society for Endocrinology BES Registration Grant, which is available to trainee scientists, as well as others trainees and students, and covers the cost of conference registration. The aim of the grant is to enable those who are still choosing their career paths, or are new to the field of endocrinology, to attend and hear the latest basic and clinical research in the field, and to network with both peers and experts. A few weeks after a straightforward, painless application process, I received an email confirming my award of the grant. While I was delighted about it, I also felt a little nervous – this was my first ever conference but I wasn’t presenting anything, and although I knew a few people who were also attending, they would be busy with poster presentations and meetings. How could I make use of all that spare time to wander around by myself?

As I made my way, on the train from Edinburgh to Harrogate (where the conference was being held), still feeling somewhat apprehensive, I read the conference programme again, and got my notebook out so that I could make a list of things that I would like to see. As I put this list together, a feeling of excitement overtook my nerves – there were such a range of different topics, including engaging with the media, cancer metabolism, food taxation, and alternative career paths. Thinking about opportunities for people at my same career stage, I also made a note to check out the Early Career Lounge.

Once in Harrogate, and too early to check into my hotel, I headed straight to the convention centre. I quickly registered and made my way to the main exhibition hall to see all the posters and exhibition stands. It was still very quiet, so I joined the coffee queue, with the intention of enjoying my caffeine kick whilst looking at the posters in more detail. To my surprise, however, a collaborator who I had not yet had the opportunity to meet in person, joined the queue behind me, and we got chatting. This chance encounter made me feel far more at ease, and afterwards I took the time to wander around. I stopped to check the posters I thought I would be most interested in, then headed to my first talk of choice, on engaging with the media, by Giles Yeo. Like most of the talks that I attended during the conference, it was insightful and engaging, and I really enjoyed being able to listen to experts in their respective fields discussing science and endocrinology from so many different perspectives.

The first evening of the conference I went to the Early Career Quiz, where I had been assigned a seat with people from my home institute, including other postgraduates and PIs. Although I’d seen the other postgraduates around the university, I’d never had the chance to talk to them, so this was a brilliant opportunity to get to know each other better and find out about the projects that everyone was working on. To our (brief) dismay, we didn’t do that well in the quiz, finishing slap-bang in the middle, but it didn’t matter – the evening was so much fun! That night I went back to my hotel feeling exhausted, but still managed to spare some energy to plan my next day.

The following morning, after a quick breakfast and a coffee, I walked back to the convention centre and went straight to the Early Career Lounge, to find out more about the Society and what was on offer in terms of career development. Whilst I want to stay in academia after I finish my PhD, I’m realistic enough to know how competitive it is, and that I need to develop additional skills away from the bench. At the Lounge I spoke with Matt Grant, the Society Careers and Engagement Officer. We chatted for quite a while, about opportunities within the Society, and about what I thought the Society could do to further support people at my career stage. At the end of our chat, I was feeling excited about the various events that I could attend, and Matt promised to email me with any opportunities that arose (which he did). The icing on the cake was, of course, the free Society for Endocrinology mug that I got after our chat…!

I would encourage anyone to apply for the Society for Endocrinology BES Registration Grant and attend this conference, as it really is a fantastic experience. I learned about areas of science that I would otherwise have missed, and met people that I would not normally have the opportunity to meet, including those from the institute that I’m based at! I’m really looking forward to staying involved with the Society, throughout my PhD and beyond!

 

Do you want to know more about Matthew’s unusual career path? Read how quitting his first PhD led him to refocus his career on endocrinology here.

Meet the Endocrinologist: V. Craig Jordan, Endocrine-Related Cancer author, reviewer and reader

Meet Professor V. Craig Jordan, Professor of Breast Medical Oncology and Molecular and Cellular Oncology at MD Anderson Cancer Center, University of Texas, leading light in cancer research, and father of the ground-breaking breast cancer drug tamoxifen.

Ever since he favoured studying pharmacology at university over drumming in a rock band, Jordan focused his efforts into developing a thriving career in endocrine breast cancer research. His current work focuses on how oestrogen-induced apoptosis can help prevent breast cancer recurrence after tamoxifen treatment. Jordan’s numerous scientific merits have led to him receiving many awards, including an OBE for services to international breast cancer research and being appointed Honorary Fellow of the Royal Society of Medicine (UK), Fellow of the Academy of Medical Sciences (UK), and Elected Member of the National Academy of Sciences (US).

Following Jordan’s guest review published in Endocrine-Related Cancer, we spoke to him about his career highlights and asked for his advice to early career researchers.

Q: What has been your proudest professional experience so far?

To date, my proudest experience has been to successfully reinvent ICI 46,474, a failed contraceptive, as tamoxifen, one of the most valuable breast cancer medicines that we have today. Back in the 1970s no one was interested in medicines that did not kill cancer, and early clinical experience with tamoxifen in metastatic breast cancer demonstrated only palliative activity. When our work started, it was chemotherapy that was on the spotlight – it was what was going to cure cancer.

My career development was accelerated by guidance from my mentors Paul Carbone, Bill McGuire, Elwood Jensen, and Harold Rusch; and the success of tamoxifen in the 1980s brought me to the University of Wisconsin, where my Tamoxifen Team discovered Selective Estrogen Receptor Modulators (SERMs). Tamoxifen was the pioneering SERM – there are now five different FDA approved SERMs for multiple indications in women’s health, ranging from treatment and prevention of breast cancer, osteoporosis, alleviation of menopausal symptoms and dyspareunia.

I have personally been delighted at the success of my Tamoxifen Team members, both in academia and the pharmaceutical industry. The development of SERMs was always a team effort, and my election to the National Academy of Science and National Academy of Medicine (and the equivalent in the United Kingdom, Fellow of the Academy of Medical Sciences and Honorary Fellow of the Royal Society of Medicine) is an honour I share with my Tamoxifen Teams.  The Tamoxifen Team is on the Wall of Honour at the Royal Society of Medicine in London.

Q: What in your working life are you most passionate about?

First of all, I am and have always been passionate about giving opportunities to the young trainees in my Tamoxifen Teams. “We are in it for life” is our team motto – over the last 40 years team members have had my support, and will continue to have it for the rest of their lives. Secondly, my academic passion is focussing on research that can potentially aid the survival of women with breast cancer. And finally, I have had a 40-year long love affair with the triphenylethylene molecule, the oestrogenic basis of the anti-oestrogen tamoxifen. I continue to have a focused interest on the relationship of SERMs with the oestrogen receptor.

Q: What most excites you about your work and the contribution you can make?

Our work on SERMs and acquired resistance to long-term anti-hormone therapy in breast cancer produced some important surprises of clinical significance. Our study of acquired resistance to tamoxifen in the laboratory resulted in our finding that, following long-term anti-oestrogen treatment (5 years), low concentrations of oestrogen kill breast cancer cells. This has clinical significance in physiology and the treatment of breast cancer, a topic which I recently reviewed in Endocrine-Related Cancer (Jordan, VC, 2015, Endocrine Related Cancer. 22:R1 – R31). Moving to the MD Anderson Cancer Center, University of Texas, provides an opportunity to extend the lives of women with new treatment strategies following the diagnosis of breast cancer. These are exciting times as it is clear that around the world our knowledge of breast cancer is accelerating. We must know our enemy in order to destroy it!

Q: What is the best feedback or advice you have ever received?

Early in my career there were two memorable moments where individuals changed my perspective.

I was not a good student during grammar school.  I had one interview at Leeds University, Department of Pharmacology, and was lucky to get into university in 1965. My goal was to use organic chemistry to develop drugs to treat cancer. However, a year into my degree I was uncertain I was doing the right courses to get into cancer research. I was then interviewed by Dr Mogey, who was to decide on my change of course. My meeting with Dr Mogey did not go well – he chose to give me honest feedback. He looked at my poor performance to date, stared at me over his half-moon glasses, and said “I don’t think you are good enough to transfer”. In response, I stood up and announced that I would become top of the third year organic chemistry course I was then doing, get a first class pass in biochemistry, and pass my physics course despite the fact I had never taken physics before. I stormed off and narrowly missed smashing his glass door as I slammed it. At that point I learned that either you chose to fight, or you fold. I chose to fight, but not to transfer courses because of my love of chemistry.

Years later I discovered two things about Dr Mogey. Firstly, he recommended me for a prestigious Ackroyd scholarship, which I won for my exam performance in my first year at Leeds. Secondly, he wrote a letter of recommendation for me to become a faculty member in his pharmacology department. Thanks to Dr Mogey’s feedback, I learned the qualities that it took to be an honest and good faculty member, and how to fight to succeed in a chosen path.

Similarly, when I was a visiting scientist at the Worcester Foundation in 1974, a Dr Eliahu Caspi called me into his office for an interview to decide, based on documented performance, whether I was to be offered a job there and not return to England. At the interview, he picked up my CV, glowered at me over his desk and stated “you don’t have a CV, because you haven’t published anything”. This hammer blow was another Mogey moment. I replied that I couldn’t publish because I had still not discovered anything. His advice then was to tell the story so far; to connect my publications together so that I could have a theme – and this became my working model.

Q: Based on your experience, what qualities or skills do you feel young scientists need to be successful?

I believe there are two essential skills that every young person must master. Firstly, without the ability to stand up and give a presentation you cannot communicate with your colleagues. Secondly, it is fundamental that you become encyclopaedic about your topic of research. The postdoctoral fellows of my current Tamoxifen Team at the MD Anderson Cancer Center are required to present historical papers from past Tamoxifen Teams – not only to hone their presentation skills, but also to learn about the development of models that we have created in the past and still use for our experiments today. After six months of presentations, I consider these trainees to be fully prepared to go into scientific meetings with enough confidence and a sound background of relevant knowledge.

Q: What advice would you give early-career researchers when thinking about publishing their work?

We return to Dr Caspi, who we met earlier in this interview and who advised me to publish. I echo his advice – if you do not publish the results you have found and tell the story so far, you have never done the work. If it’s not in print, it never happened; and you cannot claim primacy of an idea.

Every ambitious young person first wants to publish in Nature or the Proceedings of the National Academy of Sciences, which I don’t think is a good plan to start with – it helps the mentor’s reputation, not the young researcher’s. When I returned to the University of Leeds from the Worcester Foundation in 1974, I decided to publish my work in the Journal of Endocrinology, the European Journal of Cancer and, since I was a pharmacologist, the British Journal of Pharmacology. Between 1974 and 1980 I published 11 referred articles in the Journal of Endocrinology. I wanted to create impact for my work on the new anti-cancer drug tamoxifen. In 1975, I attempted to publish three papers on tamoxifen in a single issue of the Journal of Endocrinology, and almost succeeded! So my second piece of advice is to attract attention, and to publish in journals from professional societies. I published my highest cited (445) scientific paper on tamoxifen in the Journal of Endocrinology; a paper that turned out to become the blueprint for all future SERMs over the next decade.

Q: What do you enjoy doing in your spare time?

For me this has always been age dependant. As a young man at Leeds University, between 1966 and 1979, I was an Army Reserve Officer in the Intelligence Corps, and remained with the Special Air Service as a Regular Army Reserve Officer until the age of 55. During the past two decades I have enjoyed the beautiful mountains of the Austrian Tyrol and international travel. During the last decade I have taken much pleasure in my library of 6,000 hardback books and, over the years, in the exchanged correspondence with several of the authors who are soldiers, scientists, TV presenters and one spy.

Q: Who do you admire most and why?

I admire individuals who, against all odds, can achieve success in an activity that advances society.

Dr Margaret Foti is the CEO of the American Association for Cancer Research (AACR), the oldest cancer research organization in the world. She initially joined the AACR as an editorial assistant for their single journal Cancer Research and became the youngest managing editor of a major scientific journal in the country. Under her leadership, the AACR membership has grown from 3,000 to 37,000 with representatives from 108 countries. The journal portfolio has grown from 1 to 8 major scientific journals. She worked for a PhD along the way and was honoured with an MD. Marge is the modern AACR.

Dr Angela H. Brodie died on June 7, 2017. Angela told her students to do research that serves to help mankind. She trained as an endocrinologist and, together with her husband Harry, discovered the first selective aromatase inhibitor. At that time no companies were interested in developing an aromatase inhibitor to treat breast cancer, so Angela did it herself. The medicine was synthesised at the University of Maryland, shipped to England and tested showing positive results. She succeeded when others would not have given battle. Her determination resulted in the development of three FDA aromatase inhibitors and hundreds of thousands of lives saved. Angela had a calm, shy personality, but a will of steel.

Members of the Society for Endocrinology get free online access to the current content of Endocrine-Related Cancer, as well as Journal of Endocrinology, Journal of Molecular Endocrinology and Clinical Endocrinology, via the Members’ Area.

Looking to publish your research? Our members also enjoy no colour or supplementary data charges when publishing in Endocrine-Related Cancer, Journal of Endocrinology and Journal of Molecular Endocrinology. Find out more about member benefits.

 

 

Conference delegate SOS – help get our research proposals off the ground!

SfE BES is all about bringing endocrine professionals together to share knowledge and spark future collaborations. This year, for the first time, delegates are invited to hear specific research proposals and contribute their insights, data or resources to really help get these fledgling projects off the ground.

Here, Dr Kate Lines, from the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, talks about her proposal to be presented at an Endocrine Network Research Incubator Meeting to further understanding of pancreatic neuroendocrine tumours. To complete her project, she needs SfE BES 2017 delegates to provide more patient samples!

My research mainly focuses on learning more about how pancreatic islet cell tumours (pancreatic neuroendocrine tumours) grow, and using this information to develop new therapies. One specific area that has begun to interest me recently is inflammation. Inflammation is a process in which the body sends cells of the immune system (or white blood cells) to specific areas to defend against foreign substances. It has now been shown that many tumours can hijack this system by releasing chemicals to lure in white blood cells. Once the white blood cells reach the tumour they are encouraged to secrete small proteins (cytokines), which help make the perfect environment for the tumour to grow. The perfect growth environment is different for different tumours, therefore the specific white blood cells and cytokines needed by each tumour is also different. Currently, not much is known about which white blood cells and cytokines are most important for supporting pancreatic neuroendocrine tumours.

I submitted a proposal for the Endocrine Neoplasia Syndromes Network Research Incubator Meeting at SfE BES 2017 that suggests examining the area around dissected tissue from pancreatic neuroendocrine tumours for these specific cells and cytokines. Once we have this information we can use it to either help diagnose the tumours (as the cytokines can be detected in the blood), or target them with specific drugs to try to make the environment less ideal for the tumour to grow. However, the trouble with pancreatic endocrine tumours is that although they can be deadly, they are also rare. This is the main stumbling block for the proposed study, as our hospital alone doesn’t have enough samples for us to be confident that the specific cells and cytokines we see are representative of those occurring in all patients.

The Endocrine Neoplasia Syndromes Network Research Incubator Meeting provides a rare opportunity for us to try to access these samples from different hospitals in different locations, which ultimately could provide a set of samples that is truly representative of all the pancreatic neuroendocrine patients in the UK. Not only could the members help by providing samples for this study, but as our work continues they could also provide further samples, such as blood, for future work stemming from this proposal. I therefore hope that the other members of the network will be as interested in this area as I am and would like to provide us with lots of patient samples to investigate. In addition, as an early career researcher it is rare to get the chance to present new ideas to my peers. I am therefore looking forward to what I hope will be an exciting and stimulating discussion on a new area of research for me.

The Endocrine Network Research Incubator Meetings will take place on Tuesday 7 and Wednesday 8 November, 07:45–08:30, come along to the Endocrine Network Meeting most relevant to your research interests and read the full scientific programme for SfE BES 2017 for more details.

To join an Endocrine Network login to the ‘My profile’ section of the ‘Members’ Area and select Endocrine Networks.

Meet the Endocrinologists: Rowan Hardy and Louise Hunter

On the countdown to SfE BES 2017 we interviewed Dr Rowan Hardy (left) and Dr Louise Hunter (middle right), both members of the Early Career Steering Group. Dr Hardy is an Arthritis Research UK Career Development Fellow at the University of Birmingham, and his research focuses on the role of steroid metabolism in chronic inflammatory disease. Dr Hunter, MRC Clinical Research Training Fellow at the University of Manchester, specialises on the interaction between the body clock and the action of stress hormones.

In this interview, Rowan and Louise tell us about their careers in endocrinology and reveal their upcoming highlights for this year’s SfE BES conference in Harrogate, 6-8 November.

Q: Would you tell us a bit more about your career so far? How did you become interested in endocrinology?

Rowan: Since my degree I have always had a passion for endocrinology and immunology. In my first post-doctoral position I developed collaborations between leading endocrinologists and rheumatologists at the University of Birmingham. Through these connections I got to combine my interests by studying the role of glucocorticoid metabolism in tissue biopsies from patients with rheumatoid arthritis.

Louise: I’ve been interested in stress hormone biology for over ten years, since doing an intercalated BSc in Pharmacology whilst at medical school. Choosing endocrinology as my clinical career was the natural way forward.

Q: How are you getting involved with SfE BES 2017?

R: At this year’s conference I will be contributing to the public engagement event, where I will be speed-networking with local teenagers to promote science and a career in endocrinology. I will also be presenting my research as an oral communication in the Bone, Calcium and Neoplasia session, as well as supporting my PhD student who is also delivering her first presentation at SfE BES.

L: At SfE BES 2017 I will be speaking about clinical academic opportunities in endocrinology, and chairing the Early Career symposium on alternative career pathways for endocrine scientists and clinicians, as well as another session on endocrinology and behaviour.

Q: What brings you to SfE BES 2017? Any particular sessions you are looking forward to?

R: I have attended this event regularly since 2006, when I began my PhD. In all that time, whilst I immensely enjoyed the science, the social and networking opportunities at the conference are always fantastic.  I am really interested in how altered steroid metabolism contributes to inflammatory bone loss, and therefore sessions featuring eminent speakers, such as Jan Tuckermann and Eugene McCloskey, on the actions of glucocorticoid on bone, are of particular interest to me. I would strongly recommend everyone to attend the plenary sessions – these are great opportunities to see the progression of truly innovative research within endocrinology.

L: This is my fifth time at SfE BES, and I would say my favourite elements are the opportunities to be exposed to a great mix of cutting-edge science and clinical talk. I’m especially looking forward to Marian Joëls’ plenary talk on the action of corticosteroids in the brain. As a clinical trainee, I find the ‘How do I…’ sessions particularly useful – they are practical and focus on questions which crop up in routine endocrine practice, rather than rare conditions that trainees may not often encounter. For example, Andrew Toogood’s session back in 2015, on managing men who take anabolic steroids, included useful tips which I’ve found helpful in my practice.

Q: What are your future plans for your work and career?

R: I wish to combine the expertise I have developed in murine models and working with patient biopsies to develop novel therapeutic approaches for preventing complications, such as muscle wasting and systemic bone loss in chronic inflammatory disease. Within the next three years I intend to apply for a Senior Fellowship.

L: In the long-term, I’m aiming to become a clinician scientist, and I’d like my work to combine nuclear hormone research with clinical endocrinology.

Q: Who do you most admire professionally, and why?

R: I most admire Professor Georg Schett. He is a world-leading rheumatologist, investigating the pathogenesis of cartilage and bone destruction in inflammatory diseases that have shaped much of the field I currently work in.

L: For my intercalated BSc project, I had the opportunity to go to the Netherlands, and spend time with Ron de Kloet’s group in Leiden. My supervisor there, Menno Kruk, was an inspiration. He’d devoted his career to understanding the neurobiology of aggression, and his passion for the field was infectious.

Q: What do you think will be the next major breakthrough in your field?

R: Understanding how local pre-receptor steroid metabolism contributes to the dysregulation of adaptive immunity and chronic inflammatory disease.

L: In circadian biology, there’s enormous potential for the application of recent research findings to clinical practice. The idea that we could use drugs, vaccines, and other interventions more intelligently, simply by administering them at the right time of day, is very exciting.

Q: Any words of wisdom fot those starting out in your field?

R: Attend SfE BES, take an interest in any of the talks taking place at the conference, and when a speaker really inspires you, take the time to speak with them after their session.

L: Don’t be afraid to approach people and ask for help or advice, even if they hold eminent positions and you’ve never met them before! I’ve found that if you’re keen and have ambition, most people are only too pleased to help.

Both Dr Hardy and Dr Hunter will be presenting at SfE BES 2017, 6-8 November, in Harrogate.  Dr Hardy’s talk ‘Glucocorticoids activation by 11beta-hydroxysteroid dehydrogenase type 1 protects against inflammatory bone loss in a murine model of chronic inflammation’ will take place on Wednesday 8 November, 16.15-16.45. Dr Hunter’s ‘Clinical academic opportunities in Endocrinology’ will be on Monday 6 November, 12.45-13.00.

Find more details about all sessions in the scientific programme, and discover more Early Career activities at SfE BES 2017 on their dedicated event webpage.

Meet the Endocrinologist: Professor Julia Buckingham

Meet Professor Julia Buckingham, Vice-Chancellor and President of Brunel University London and 2017 Society for Endocrinology Jubilee Medal winner. Professor Buckingham’s work focuses on the mechanisms controlling the hypothalamo-pituitary-adrenocortical (HPA) axis. Her outstanding work together with her contribution to the Society, of which she was President from 2009 to 2012, has led to her being awarded this medal, to be presented the annual conference, SfE BES 2017, in Harrogate, 6-8 November 2017. In this interview, Professor Buckingham tells us about her journey in endocrinology.

Q: Can you tell us more about your career path and research interests? 

I developed my passion for endocrinology as an undergraduate student at Sheffield University, where I was inspired by my amazing teachers.  My love for pharmacology, triggered by a short spell in the pharmaceutical industry, came later, before I started my PhD.  Since then I have worked in both endocrinology and pharmacology and have remained firmly wedded to academia. Throughout my career I have combined research and education, and I passionately believe that the two are symbiotic. In fact, I get very cross with people who are ‘too posh to teach’ – we all have a responsibility for the next generation, just as previous generations did for us.  I have had enormous fun over the years working with my research group (and contributing a little bit, I hope!) to our knowledge and understanding of the HPA axis.  I have also been privileged to work with the broader academic community – research funders, publishers, learned societies, particularly the Society for Endocrinology.  Looking back on my career, I think I have probably always been interested in leadership roles, although I didn’t think about it in those terms.  My previous role as Pro-Rector for Education at Imperial College London opened my eyes to the broader issues facing higher education in the UK and internationally, and that led to my current role as Vice-Chancellor of Brunel University London.

Q: What specifically are you presenting at your Jubilee Medal Lecture at SfE BES 2017?

At the conference I will be talking about the complex relationship between the host-defence system and the HPA axis. I will specifically focus on the role of a family of receptors, which were first identified as targets for formylated bacterial peptides, and which contribute to the pathological response to infection.

Q:  What are you particularly looking forward to at SfE BES 2017?

The programme is fantastic as always, and it is difficult to choose.  I always try to go to the plenary lectures and I am particularly looking forward to brushing up my knowledge of POMC processing.

However, the most interesting insights you can get at these events often come from talking to people who are presenting posters, so I would urge everyone to spend time doing that.

Finally, I look forward to catching up with old friends and colleagues, of course.

Q: What has been your career highlight so far?

My research team would say it is seeing new data – and they would go to great lengths to wind me up by telling me they’re not sure how an experiment has gone because they haven’t worked the results out yet! But if you ask me, the greatest highlights are always when seeing someone in my team do well and progress to the next stage of their career, and as Vice-Chancellor, seeing the pride and joy of parents from across the globe when their sons and daughters collect their degrees at graduation.

Q: What are your future plans for your work and career?

I am very focused on my work at Brunel at the moment and I haven’t given much thought as to what comes next.  Theoretically it should be retirement, but I can’t imagine that – when my time at Brunel comes to an end I shall be looking to do something else!

Q: Who do you most admire professionally?

That’s a very difficult question as I have met so many hugely impressive people in different walks of life – it would be unfair to pick one.

Q: Any words of wisdom for aspiring endocrinologists out there?

Follow your passions, keep an open mind and don’t let a hypercritical referee’s report get you down.

Q: What do you think will be the next major breakthrough in your field?

If I knew the answer to that I would be working on it now!

 

You can attend Professor Buckingham’s lecture, ‘Bacteria, steroids and formyl peptide receptors – more twists to the inflammatory response’, at SfE BES 2017 on Wednesday 8 November, 16.15-16.45. See more details in the scientific programme.

Meet the Endocrinologists: Miriam Asia & Andrea Mason

Miriam Asia (right) and Andrea Mason (left), Clinical Nurse Specialists (CNS) in endocrinology at Queen Elizabeth Hospital Birmingham (QEHB) tell us about their work in endocrine nursing and what they are looking forward to at SfE BES 2017, 6-8 November in Harrogate.

Q: Tell us a little about yourself and where you work

Miriam: As an endocrine specialist nurse, I run the adrenal nurse-led clinic, post-traumatic brain injury endocrine screening clinic and support the young adult clinic. I have also completed the Non-Medical Prescribing course at Masters Level and I am planning to start a masters in endocrinology.

Andrea: I currently look after three nurse-led clinics; late effects of cancer treatment (transition clinic from children’s to adult services), pituitary and a new clinic that monitors patients who have developed immune-related adverse events in response to immune check-point inhibitor treatment. I have a particular interest in the quality of life issues surrounding endocrine conditions.

 Q: What inspired you to work in endocrinology?

Miriam: I only knew about endocrinology through nursing textbooks but now, being able to see endocrine patients, reviewing them in clinic and working with them through their endocrine journey makes me realise even more how fascinating and exciting endocrinology is. Especially when I see the difference it makes to our patients during and following treatment.

Andrea: During my nurse training I developed a keen interest in cancer nursing and worked in oncology for many years until an opportunity for me to branch out into endocrinology as a Clinical Nurse Specialist arose. This position was to cover maternity leave and I knew little about endocrinology, so I had to learn on the job quickly! During my first week, I attended the Society’s Endocrine Nurse Update and was totally blown away by the specialty. The journey had started; I spent evenings studying after work trying to get to grips with the basics.

 Q: What are you looking forward to at SfE BES 2017?

Miriam: As well as the plenaries and nurses’ sessions, I am also looking forward to the ‘Meet the Expert’ and ‘How Do I…’ sessions, especially those relevant to my clinical practice.

Andrea: This is my second SfE BES and I am looking forward to the nurses’ sessions, particularly those on opiate-induced endocrinopathy, and development of endocrinopathy following metastatic melanoma treatment. I also enjoy meeting and networking with other endocrine nurses.

Q: What are your career highlights so far?

Miriam: I recently completed a sky dive (see photo right), with some of my CNS colleagues, in support of our QEHB charity for the Young Adult Clinic!

Andrea: Highlights in my nursing career, include working as an Endocrine Nurse Specialist and successfully completing the Non-Medical Prescribing course at Masters Level.

Q: Who do you most admire professionally and why?

Miriam: My endocrine colleagues – nurses and doctors – at QEHB who work with such competence and dedication to look after our endocrine patients

Andrea: I have had an inspiring and passionate Endocrine Lead Nurse to guide me throughout the last five years and support my development. I have also had the support and patience from a caring team of endocrinologists.

Q: What advice would you give to someone starting out in endocrine nursing?

Miriam: Although endocrine nursing is a challenging specialist role that requires a lot of reading and studying, it is rewarding in the end.

Andrea: It does take time to understand the speciality and additional studying is required but when you understand the basics of the endocrine system, it is all very logical. I would say to any nurse…. go for it!

Q: What are your future career aspirations?

Miriam: To complete my masters in endocrinology and become more confident and competent in dealing with complex endocrine cases as a result. I also hope to see more nurse consultants and nurse led clinics being set up.

Andrea: My future plans are to remain in my current position and I am looking to complete a master’s degree in endocrinology.

Don’t miss the dedicated Nurses’ Lounge at SfE BES 2017, giving nurses the opportunity to meet and network in their own space. This is especially beneficial when you are travelling on your own, or if you are a first-time attendee, as there is nearly always somebody there to chat to. At designated break times there is at least one member of the Nurse Committee on hand for you to get to know.

Follow the links to find out more about SfE BES 2017, view the scientific program and register online.