Giles Yeo is a Principal Research Associate in the Metabolic Research Laboratories at the University of Cambridge, Director of Genomics/Transcriptomics for the MRC Metabolic Diseases Unit, and a convenor of the Society’s Neuroendocrinology Endocrine Network.… More
Meet Professor Antonio Vidal-Puig, endocrinologist and Society for Endocrinology Medal winner for 2017. Prof Vidal-Puig is based at the Institute of Metabolic Sciences, Cambridge University and at Addenbrooke’s Hospital, where his outstanding research, focusing on the link between obesity and associated metabolic complications, has earned him this award, to be presented the annual conference, SfE BES 2017, in Harrogate, 6-8 November 2017. Learn more about his endocrine journey in this exclusive interview.
Q: Tell us a little about your career so far and how you ended up in Cambridge.
Originally from Spain, I studied medicine and trained in endocrinology at Valencia Medical School and Granada Medical School. I held post-doctoral positions in Boston at the Massachussetts General Hospital and Beth Israel Hospital/Harvard Medical School from 1992-1999. There I had excellent mentors including Jeff Flier, Brad Lowell, David Moller and Leo Krall. This was a very intense, exciting and uncertain period, at the epicentre of major discoveries in the field of obesity. This was a period that defined my career, scientific focus, approach to science and reinforced my values. I have been developing my career in the UK, since arriving at Cambridge University in 2000, and now have an established laboratory and have become a Professor of Molecular Nutrition and Metabolism.
Q: Tell us more about your research that led to you being awarded the Society Medal
The lab is interested in why obesity results in diabetes, insulin resistance, fatty liver and ischaemic heart disease, in order to find ways of preventing these complications.
The key concept of our programme is lipotoxicity, which links obesity-related metabolic complications with the excessive accumulation of lipids outside adipose tissue, in organs including muscle, liver and heart. From the concept of lipotoxicity we have developed three main research directions:
- understanding how the adipose tissue works, with the aim of improving its function and ensuring that lipids remain in adipose. This led to the development of our “adipose tissue expandability hypothesis”, which is now widely accepted by the scientific community
- developing strategies to burn the excess lipids and prevent lipotoxicity through activation of brown fat
- promoting that the quality of dietary lipids should be as healthy as possible, to prevent toxic effects.
My Medal Lecture at SfE BES 2017 will summarise our contribution to these three directions.
Q: What are you particularly looking forward to at SfE BES 2017?
I will use this conference for updating clinical aspects of my work. The presentation quality is always good and helpful. One session I am really curious about is Workshop 1: Tissue Engineering for Regenerative Medicine in Endocrinology. I think technology is essential to retain a competitive position in research and the topics presented are highly transferable and of interest. I think tissue engineering approaches to increase brown fat mass could be really helpful in preventing obesity and diabetes, I am curious about the concept and possibilities of using 3D bioprinting.
Q: What have been your career highlights so far?
I feel content about my career progression. I consider highlights to be our best pieces of research; our papers tend to be quite comprehensive and we believe they make important contributions. I think for this reason these contributions are well respected by our colleagues. Our reputation as a lab is important for us. Also as a proud introvert, I have not touted our highlights and have not needed to for our professional highlights to be widely acclaimed, however I do understand that it is important to make the public aware of their implications. Also, as a laboratory leader I know that to disseminate these highlights is important for the careers my lab members. In this respect, winning the Society for Endocrinology Medal is a highlight that reflects the quality and commitment of the present and past members of the laboratory.
At a more personal level, I admit I have an aesthetic approach to science. I enjoy understanding and identifying sophisticated mechanisms, developing models that explain reality and learning how biological systems self-regulate. I don’t think this is unusual amongst endocrinologists. Also, becoming a Professor at Cambridge University was a moment of satisfaction I shared with my colleagues and family. In some ways my career has provided me with professional freedom, which is a key value for me, beyond other motivations, such as power or fame, that I have always found energy draining and restrictive of my autonomy.
Q: What do you think are the biggest challenges in your research area right now?
I think a big challenge in my research area, and others, is how to extract value from the excessive information generated by recent technological advances. Our challenge is how to analyse this information to prioritise the types of mechanistic validation that are necessary for estimating its relevance. Also, it is not only the amount of data, but the amount of unnecessary noise coming from poor quality research that makes this task more difficult.
Q: What are your future plans for your work & career?
As you become more senior in science, you often suffer the disadvantage that your professional horizon is shorter. However, this position also has the advantage that you can be more selective in your choice of projects, with more freedom to take risks. I think my laboratory in this respect is quite entrepreneurial, we are innovating by entering new fields/technologies, which I think is important for remaining competitive. For example, we have opened a new lab at Sanger, funded by the European Research Council to work on stem cells and adipose tissue. We are also developing two new programmes of research; one in Nanjing focused on murine models of fatty liver, and another in Bangalore focused on adipose tissue stem cell biology to model obesity and diabetes in India. These are exciting challenges that will provide opportunities for my younger associates in their future careers.
Q: Who do you most admire professionally?
I have learned a lot from many of my mentors, colleagues and trainees. In some way these experiences have shaped my values and my strong views about science and leadership. For example, I have always admired the intellectual rigour and scientific honesty of Brad Lowell. I admired the consistency and confident leadership of Jeff Flier and the legacy of Daniel Lane, who developed many academic scientists in his lab to share his cultural values and collegiality, which they now disseminate to the next generations. I find this very impressive.
Q: Any words of wisdom for aspiring endocrinologists out there?
Endocrinology is not a specialty that will make you rich, but it is a specialty where you can fulfill your intellectual scientific needs and enjoy the human aspect of practicing medicine. It is very satisfying because your patients get better and, given that treatments are required long term, an important factor in the success depends on establishing an empathetic relationship with them. You will get to know many of your patients well, from whom you will receive gratitude and a sense of meaning and fulfillment. In this respect it is a very rewarding profession.
Q: What do you think will be the next major breakthrough in your field?
I think real breakthrough with long term impact requires deep knowledge and new technologies, I have become quite sceptical about quick or easy breakthroughs that address complex problems. It is important to understand how regulatory systems operate, to learn what the adaptive changes of the organism or cell to maintain normality are, and to determine the intrinsic capacity of these systems to recover normality if the early factors of the disease are removed. For this reason, we focus on early disease events, aiming to prevent or reverse excessive damage to the homeostatic system and regain metabolic control. In this sense, we think it is as important to learn how the problem occurs as it is to learn the trigger and why it occurs. In our field I think understanding how lipids mediate disease could be used for prevention, early diagnostic and therapeutic purposes.
You can hear Prof Vidal-Puig’s Society for Endocrinology lecture on Wednesday 8 November, 15:45-16:45, and see the full scientific programme for SfE BES 2017.
Kevin Murphy is Professor of Endocrinology & Metabolism at Imperial College London and a convenor of the Society’s Metabolic and Obesity Endocrine Network. His research focuses on the role of the hypothalamus in the control of energy homeostasis and reproduction, and in this interview he tells us more about his research and career.
What inspired you into endocrine research?
I moved to London with a BSc in Zoology and Physiology, and for three months, applied for every job in London that needed a BSc but no experience. I was lucky enough to have an argument about what killed off the dinosaurs with an interviewer in the Endocrinology Unit at Imperial College that we both enjoyed, and was given a technicians job. Over the following year, I realised that I was really interested in how hormones influenced behaviour, especially feeding behaviour. And it’s been downhill ever since…
Tell us a little more about your current research
I’m interested in how the gut senses macronutrients, and in particular protein, to regulate appetite and metabolism. I’m excited about using approaches such as metabolomics to investigate how foods are detected to change food intake – for example, comprehensively measuring the changes in the thousands of different metabolites produced in the gut following digestion of a particular food, and investigating how they might drive gut hormone release.
What do you think will be the next big or important advances in metabolic research?
The use of genome-wide association studies to identify and establish novel causes of obesity have really advanced the field. Linking big genetic data to the physiological effects of the genes will be important to further advance the field.
The explosion of information on the role of the microbiome in energy homeostasis and metabolism is also having a great impact, as are new tools for manipulating endocrine cell function. I think establishing reliable pharmaco- and optogenetic method equivalents for endocrine cells will be a big breakthrough in metabolic research.
What do you think are the biggest challenges faced by academic science?
Convincing an increasingly disillusioned public that there might be an objective truth behind particular issues is a big challenge for all scientists.
For newcomers to scientific research, I think it is hard to establish a career. To get a PhD studentship these days, you need to have been polishing your CV from the age of 13. And then there aren’t a lot of academic jobs to go for when you are a post-doc.
For older researchers, funding and juggling different aspects of their job makes it difficult to maintain a career over the long term.
What do you enjoy about being a Network convenor?
It’s nice to hear from other Network members at the meetings, and to maintain the profile of obesity and metabolism at the annual SfE BES conference.
Do you have any words of wisdom for aspiring endocrinologists?
I’m not sure how wise they are…but think about what evidence you have on your CV to show you can do certain things (attract funding, teach, manage a project) and try to get some experience if you don’t have any. Get a feel for how the science funding system works, as this is really helpful later in your career. Make sure you enjoy the work, otherwise there are lots of other fulfilling careers you could probably pursue with less effort. Join the Society for Endocrinology…
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.
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.
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.
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.
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 Dr Nigel Page, Director of Learning and Teaching at the School of Life Sciences, Pharmacy & Chemistry, Kingston University London. Nigel also dedicates his time to promoting endocrinology, both within his school as a Society Endocrine Ambassador, and outside as a Public Engagement Committee member. Such engagement with the Society could not go unnoticed, so we approached Nigel to ask him about his career and his enviable drive to nurture a passion for endocrinology in others.
Can you talk us through your first steps in endocrinology, and how you got to where you are now in your career?
After graduating in Biological Sciences (Molecular Biology), I completed my doctorate within the Department of Zoology at the University of Reading. My early research career was focussed on the development of transgenic birds and mice; and it was not until 1997 that I was properly introduced to endocrinology, when I undertook a postdoc in the laboratory of Phil Lowry. At the time, work in the laboratory was very much around corticotrophin releasing factor and its binding protein, and adrenal growth. However, a chance visit to the university by Isaac Manyonda, Consultant Obstetrician at St George’s Hospital, London, led to the development of a project that would push the lab, and also my career, in a new direction. Within two years, my project started to yield results that led to the proposal for a role of neurokinin B in pre-eclampsia, the discovery of endokinins and their gene-related peptides, and pregnancy associated plasma protein-A2/E and its splice variants. These were exciting times that coincided with the human genome project nearing completion. Routine bioinformatics was just at the cusp – many researchers were still nervous of it, so the thought of stepping outside of the wet lab and onto the computer for nine months was something unheard of. Subsequently, I spent a lot of time exploring placental cDNA sequences of the fledgling tentative human consensus sequence databases. Phil Lowry used to say that research tends to be cyclic, moving from molecular biology of genes to whole organism physiology and back again – and he was right. It was not long before I realised that being an endocrinologist also required developing my skills in protein purification, chromatography, immunoassays, ligand binding and cell signalling.
In 2006, I was appointed Senior Lecturer at Kingston University London. There, I took much of my first-hand experience to the forefront of my undergraduate teaching, in areas such as the hormonal control of metabolism, protein purification and bioinformatics. My main research area remains in reproductive endocrinology, where I have maintained a small research group and continue to work on gestational disease looking at variations in mRNA splicing, precursor processing and posttranslational modifications of placental peptide hormones. Since 2014, I have been an associate professor, and more recently I have been appointed Director of Learning and Teaching for the School of Life Sciences, Chemistry and Pharmacy (at Kingston), a role that has also led me to participate in a range of pedagogic research projects.
What in your working life makes you happiest?
“I am lucky to have a role that combines both research and teaching. Some of my happiest career moments are those that start with informal chats about research with my students, and lead to a genuine passion and thirst for them to learn more.” – Dr. Nigel Page
I am passionate about creating inclusive scientific communities – I conceived my School’s ‘Discover Research’ fayre, where our undergraduate students get to meet and interact with our research teams. I also had the pleasure of organising and running the Royal Society of Biology’s HUBS Workshop, on implementing inclusive learning and teaching in the biosciences. When it comes to my research, I get most passionate about deciphering the reasons for the differential processing of hormone precursors in different health states, and the determination of the role of posttranslational modifications. Also, from recent collaborative work with parasites, I would like to understand more about the role of endocrine interactions in the host-parasite relationship.
What do you find most fulfilling about being an Endocrine Ambassador?
For many years I was the informal contact for the Society at Kingston, and encouraging new members to engage with the Society was a big part of that. One year, I even received the Society’s accolade for recruiting the most number of new members, as well as helping to recruit some of the first students to the Society’s Student Ambassadors Scheme! So, when the opportunity came along to become an official Endocrine Ambassador and champion endocrinology within my institution, I took it. Kingston has several interdisciplinary research groups, including those involved in diabetes, cancer, drug discovery and delivery, sports science, and nutrition. With the funding opportunities offered to Endocrine Ambassadors, we could organise an event to bring together many of the different flavours of our endocrinology community. Our invited keynote speaker was Gary Frost from Imperial College, who presented on ‘Fermentable carbohydrate-driven appetite regulation in the brain’, and the event was a great success. Overall, being an Ambassador has certainly afforded me the opportunity to get more people involved, stimulate debate, and hopefully convince a few more people of the benefits of being part of the endocrinology community via the Society.
Can you tell us about your involvement with public engagement?
In terms of public engagement, having media exposure of one’s own endocrine work came as part and parcel of having worked in Phil Lowry’s laboratory – I still remember the days when BBC and ITV camera crews used to turn up to the lab! Nonetheless, this was not the reason that drew me to being part of the Society’s Public Engagement Committee. Like many academics, I actively participate and engage with a variety of activities in schools and colleges to promote the biological sciences. I am also a STEM ambassador and work as my institutions’ STEM Insight placement co-ordinator, providing teachers with real-life knowledge and experience to bring careers to life in the classroom. But I also wanted to encourage my own students to have a more proactive engagement with their professional societies, and when I found out that the Society was seeking volunteers to take part in public engagement at a Big Bang Fair I jumped at the chance, also encouraging three of my students to come and participate. We all had a fantastic time – I was impressed and wanted to do more! Subsequently, I was nominated to the Public Engagement Committee. So far, my roles have included updating and editing You and Your Hormones, the public facing website of the Society, and reviewing potential press releases for the Society’s annual conference, SfE BES. For me, the most fulfilling part of it all is helping to create and develop new perspectives in public engagement that have a real impact on society.
What have been your proudest professional experiences so far?
I am proud to have been at the forefront of some quite novel and exciting discoveries in endocrinology over the past few years, with publications in leading journals including Nature and Proceeding of the National Academy of Sciences. I also feel privileged to have worked with some very talented and inspiring scientists over the years.
If anyone had told me, in the earlier stages of my career when I lived life between short-term postdoc contracts, that I would be part of the senior management team running a large university department, I would never have believed them. Today, if you ask me about my proudest moments, I’d say they are seeing my students doing well, seeing the pride and joy on the faces of their family and friends at graduation, and being able to nurture the next stages of their career journeys.
Who do you admire most?
Not an easy question to answer – I have met so many people over the years that I have respect for, have learnt so much from, and who have shaped my values. Professionally, I do admire the competence and support of my colleagues, and the dedication and resilience of my students, in what must be tougher times than when I was at university.
What do you enjoy doing in your spare time?
In 2008, I set myself the goal of travelling the whole of Britain by train, and I am currently about two thirds of the way to completing it. The only problem is that the bits I need to complete keep getting further away! Perhaps the location of SfE BES 2018 in Glasgow later this year will help with that…
If you weren’t a scientist, what would you be?
One of my students recently told me that I should be an event manager, as I always appear to be organising things, but I would not swap that for a minute with the multifaceted role of being a university academic. On a more serious note – I nearly did pursue a graduate career in retail management, but my PhD mentor, Ken Simkiss, steered me back to science. For this I am truly grateful to him – I have never looked back since!
Do you want to inspire others to pursue endocrinology, too? Find out more about being a Society Endocrine Ambassador.
What a year 2017 has been! Although the bar was set high in 2016, this year was just as prosperous and filled with accomplishments, thanks to the work of all those who are part of the Society.
Here are some of the things your Society achieved in 2017…
1. Doubled the number of users of You and Your Hormones, our public facing website
The Society’s commitment to disseminating accurate information and expertise to non-specialists has been fruitful this year. In July, a more engaging, easier to navigate, and optimised for mobile viewing version of the You and Your Hormones website was launched. Since then, the number of visitors has more than doubled!
2. Made it easier for members to publish Open Access
At the start of the year, Society members were gifted with free Open Access publishing in Endocrine Connections, leading to savings of up to £950 per publication, and encouraging members to support this high quality, peer-reviewed journal in its aim to be the leading Open Access title in the field. In June, the journal received its first impact factor of 2.541. Over the course of 2017, journal submissions have doubled, and published articles have increased almost four-fold!
Find out all about this and other member benefits on our website!
3. Launched the new Endocrine Nurse Grant
In order to support our nurse community, the Society’s Nurse Committee developed the Endocrine Nurse Grant, a new grant aimed at furthering nurses’ careers and improving nursing and clinical practice.
4. Identified our first endocrinology champions!
Aimed at advancing the discipline and increasing the profile of endocrinology, the Endocrine Ambassador scheme was launched this year. By organising small research seminars in their home institutions, and representing and promoting the Society for Endocrinology, our Endocrine Ambassadors champion endocrinology and help to increase interdisciplinary collaborations.
5. Received outstanding impact factors for Society journals
2017 has been an excellent year for Society journals – all of them receiving strong impact factors that contributed to keep making these journals a reliable, high-impact home to publish the best science.
Endocrine Connections received its very first impact factor – an impressive 2.541. Journal of Endocrinology’s impact factor was its highest to date at 4.706, positioning the journal as the highest ranked basic science endocrinology journal for two years in a row. The Journal of Molecular Endocrinology’s impact factor increased an impressive 21% to 3.577, making this journal the leader in its field. Endocrine-Related Cancer received 5.267, its highest impact factor since 2003. The journal remains in the top quartile of both the oncology and the endocrinology and metabolism categories. And last but not least, Clinical Endocrinology received a strong impact factor of 3.327.
6. Helped improve media reporting of over 120 endocrinology-related stories
This year, the work of our Media Ambassadors, members who provide comments or advice to help journalists cover endocrinology-related topics, have helped improve science and health media reporting for over 120 stories, a 50% increase on last year!
Check out some examples of how our Media Ambassadors have helped journalists this year.
7. Empowered our members to meaningfully engage with non-specialists
Engaging with wider, non-specialist audiences is increasingly more important amongst the scientific and clinical community. It can deepen the impact of your work in the community, and it is also expected of higher education institutions. To help equip members with the skills needed to approach public engagement successfully, we offered two free-for-members, full-day workshops: an Introduction to Public Engagement session run by the National Co-ordinating Centre for Public Engagement (NCCPE), and a Media Interview Training session run by Boffin Media. Both workshops were highly rated by participants, and were described as comprehensive and highly professional.
Outreach training opportunities are advertised on the Society website – be sure to check it out for updates!
8. Facilitated information sharing amongst the Endocrine Networks
We love to encourage community-building, and understand that our membership has diverse interests with different needs. To facilitate the work of the Endocrine Networks, in 2017 we established the Endocrine Network webpages – dedicated hubs for knowledge exchange amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses that work in particular specialist fields.
To further promote interdisciplinary collaboration, SfE BES 2017 also introduced the Endocrine Networks Research Incubator Meetings, where a selection of research ideas were presented to a panel of experts and the audience, in order to get constructive advice, identify collaboration opportunities and get new research ideas off the ground.
Wondering how to get involved? Joining an Endocrine Network is easy – just log into the Members’ Area and select ‘Endocrine Networks’.
9. Kept you updated on the latest in the endocrine world
This spring, we offered our membership exclusive access to Society event abstracts in the new volume of Endocrine Abstracts: Society for Endocrinology Endocrine Update, which included abstracts from National Clinical Cases, Obesity Update and Clinical Update.
10. Promoted the success of your endocrine units, and worked together to overcome challenges
The Society Interdepartmental Peer Review scheme is an opportunity to improve the work of endocrine units, and achieve better clinical practice for clinicians, nurses and patients. Relaunched this year, the scheme allows centres to identify their strengths and weaknesses, and work collaboratively to support the changes needed to facilitate the delivery of best care, backed by sustainable services.
Read more about how the scheme can help strengthen endocrinology.
We can’t wait to see what 2018 holds in store for us all…
Happy holidays and happy New Year!
Meet Dr le Roux, Consultant in Metabolic Medicine at Imperial College London and Chair of Experimental Pathology at University College Dublin. During his career, he successfully established an independent research group and has been an important influencer in the field of metabolic medicine. His research focuses on diabetes and obesity, specifically the increased morbidity and mortality associated with these conditions.
Dr le Roux will be speaking at Obesity Update 2018, in the debate ‘Will metabolic surgery replace pharmacotherapy for the treatment of type 2 diabetes?’ Ahead of the event, we interviewed him to find out more about his career path, research interests and his position in the upcoming debate.
Q: Tell us more about your background and career highlights so far?
I am a metabolic medicine physician with an interest in obesity; specifically in how bariatric surgery and pharmacotherapy can improve patient outcomes. I graduated from the University of Pretoria and completed my specialist training in Metabolic Medicine at St Bartholomew’s Hospital and Imperial College. I was awarded a Wellcome Clinical Research Fellowship and completed my PhD at Imperial College. I then received an NIHR Clinician Scientist Award, which enabled me to set up the Imperial Weight Centre, and was then offered a Chair at the Diabetes Complications Research Centre at University College Dublin. The proudest moment of my career was receiving the President of Ireland Young Research Award at Áras an Uachtaráin.
Q: What are you currently working on?
My research investigates using a combined approach of bariatric surgery with pharmacotherapy to reverse the complications of diabetes. We are aiming to treat people with diabetic complications, e.g. diabetic kidney, renal, neural or cardiovascular disease, with both surgery and medication to put these symptoms into remission and stop the development of the disease.
Q: What most excites you about your work and the contribution you can make?
I am most excited about the opportunity to hear what obese patients report about their disease, and applying this knowledge together with basic and clinical science to pursue these symptoms and understand the mechanisms of obesity. I am also excited about the progress we have made in the field; for example, the discovery that obesity is a subcortical brain disease opens up new treatment options, while also reducing the discrimination that patients suffer.
Q: The theme of the 2018 Obesity Update debate is whether surgery is more effective than pharmacotherapy in the treatment of type 2 diabetes. Can you tell us why there is a difference of opinion on this?
Until recently, bariatric surgery – that is gastric by-pass or sleeve surgery – was not considered to be a viable treatment for patients with type 2 diabetes. However, a systematic review of 11 randomised controlled trials, published in 2013, showed that those who undergo surgery do better and outperform patients on pharmacotherapy for weight loss, glycaemic and blood pressure control. This, of course, has great implications for type 2 diabetes patients.
Given the aforementioned trials and their results the question becomes: should every type 2 diabetes patient be offered surgery as a treatment? However, the issue here is not really whether or not we should use surgery – but if and when bariatric surgery is the best strategy to follow.
Q: You will argue that surgery cannot replace pharmacotherapy but, if surgery is so successful, why not?
The main issue is that not all patients with diabetes are the same – the risks of morbidity or diabetic complications are extremely varied and thus, their treatment options should accommodate these differences and find a balance between the risks and gains of bariatric surgery vs. pharmacotherapy.
Although the risks associated with surgery are very low, they still aren’t as low as those associated with medication. Considering this, patients at high risk of diabetic complications for whom best medical treatment is not sufficient may hugely benefit from surgery. On the other hand, for those patients who respond positively to pharmacotherapy there is little value in offering surgery as well.
Additionally, we must not forget that pharmacotherapy is constantly improving. Due to such advances, if we had a randomised controlled trial today that compared outcomes between surgery and medical care, it would be very difficult to imagine that surgery would have any additional benefits beyond best medical care when it comes to mortality. We’d love to say that if you have an operation you’re going to live longer but we simply don’t have that evidence. However, we do have evidence to say that using drugs, such as a sodium-glucose co-transport inhibitor or a GLP-1 analogue, will help diabetes patients to live longer.
Q: In your opinion, when would bariatric surgery be appropriate?
We should offer surgery when it adds value to the patients – helping them to lose weight, and achieve better glycaemic and blood pressure control – and to facilitate the work of diabetologists that treat these patients. It’s not about surgery against medicine, it’s about how surgery can make medicine better. This is precisely what’s done in cancer therapy – we use surgery to control the disease, then chemo or radiotherapy to keep it in remission. We don’t expect surgery to be sufficient on its own – after surgery we still follow the patient and make sure to control all the other consequences of the surgery.
In summary, the model should shift to actually using surgery as an add-on therapy to pharmacotherapy. This way, the benefit of using surgery is that patients need much lower doses of medication. It may allow someone who needs insulin to control type 2 diabetes to move on to requiring only metformin or other oral medications. That would be a massive improvement for the patient’s quality of life. Taking it a step further, a patient with fully controlled diabetes on oral medication could use surgery to put diabetes into remission, and then use a lower dose of metformin to keep the diabetes in remission.
Q: How do you think this debate be resolved?
I think we will all agree that more surgery should be offered to patients; and that we need to use this combined treatment model more frequently in patients with diabetes, especially for those that would benefit most. However, it is how this cohort of patients will be defined that will provoke further debate.
Q: What do you enjoy doing in your spare time?
I have recently started sailing Flying Fifteens and am currently training to qualify for the World Championships in 2019.
Q: Who do you admire most and why?
Rodin – as a sculpture artist he was able to communicate very complex concepts using the human body, but he did so in a simplistic way that influenced how people thought, thus moving civilization forward.
Obesity Update 2018, an event sponsored by the Society for Endocrinology and the Association for the Study of Obesity, will be held in London, 1 February 2018. Register now to attend.
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).
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.
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.