Professor Adrian Clark is an Honorary Professor of Endocrinology at Bart’s & the London School of Medicine & Dentistry, and Chair of Bioscientifica. He enjoyed a varied academic career in endocrinology, from studying at Bart’s Medical College to becoming Head of the Academic Department of Endocrinology at Bart’s. He is the current editor-in-chief for Endocrine Connections. In our interview he discusses his academic career, the importance of resilience in research, and tells us what we can expect from his SfE BES 2022 lecture.
Tell us about your career so far
I trained in medicine and biochemistry at Bart’s Medical College, and following various junior clinical training positions, took up a research position with Harry Keen at at Guy’s Hospital Medical School before moving to the National Institutes of Health (NIH) in Bethesda, USA to work on cloning the epidermal growth factor (EGF) receptor with Ira Pastan. I subsequently moved to Kevin Catt’s lab at NIH, working on cloning the angiotensin receptor, before returning to London to Mike Besser’s Department of Endocrinology at Bart’s to establish the Centre for Molecular Endocrinology with Medical Research Council support. I later became Head of the Academic Department of Endocrinology on Mike’s retirement, and Deputy Director of the William Harvey Research Institute. I took on the post of Dean of Research at St George’s University of London in 2012 before retiring from full time work in 2015. Since then I have maintained my research involvement at Bart’s and been Chair of Bioscientifica since 2017. I was editor-in-chief of the Journal of Endocrinology andJournal of Molecular Endocrinology for 6 years, and now I’m editor-in-chief of Endocrine Connections.
What attracted you to endocrinology?
Endocrinology provided ‘precision medicine’ decades before the term was even invented. It was the ability to apply objective data to the diagnosis and management of human disease in contrast to all other medical specialties at the end of the last century that was perhaps the main attraction. In addition, the opportunity to understand disease processes as aberrations of biology really brought science and medicine together in a manner unequalled at that time, which appealed to the basic scientist in me.
Who has inspired you most in your career?
This is impossible to answer. I have worked with, and been taught by, many great endocrinologists over the years – Mike Besser – whose teaching sessions as a medical student were legendary, Lesley Rees, Steve Bloom, Harry Keen and Kevin Catt, to name a few. My greatest “inspiration” however was at a University of Exeter open day as a seven year old when I visited the biology department. I can still remember my amazement at the many exhibits there, such as viewing living protozoa under the microscope. My parents had to drag me away.
What are you most proud of academically?
In research, pursuing the idea that the adrenocorticotropic hormone (ACTH) receptor required an adrenal co-factor when precedents were lacking, and for eventually discovering this co-factor through a rather unexpected route. Perhaps a greater achievement, though, is maintaining a research environment that trained many outstanding researchers and leaders in endocrinology in this country and abroad!
What do you think are the biggest challenges in your field?
Research funding, and attracting and supporting talent. Research in endocrinology understandably lacks the mass appeal of cancer, brain or cardiovascular research. Arguably, this means that funded endocrine research has to be of greater quality, but it also means that endocrinology can be a tough and discouraging place to establish a career at the post-doctoral and junior faculty level. Added to this is also the probability that the attractions of studying and working in the UK will be significantly reduced since Brexit, depriving us of the wealth of European talent from which our research has undoubtedly benefitted in the past.
Where do you see the next breakthrough happening in your field?
I think that with the greater understanding of the molecular mechanisms underlying signalling we are on the brink of development of really sophisticated tools that could be used to manipulate the pituitary-adrenal axis in patients.
Can you tell us about your SfE BES 2022 lecture?
I aim to summarise about three decades of work which led to the discovery and understanding of the unique role of the melanocortin receptor accessory proteins (MRAPs) and to highlight a couple of underexplored aspects of their role in the control of adrenal function.
Do you have any words of wisdom for future endocrinologists?
Resilience, when papers and grant applications are rejected, it is an essential requirement for success. Ask questions – those you fear are silly questions are often the most revealing. Find and keep a mentor you trust. Keep abreast of developments in other areas – they sometimes provide you with remarkable insights and even real “eureka” moments.
You can attend Professor Adrian Clark’s Jubilee Medal Lecture “The MRAP Files” on Tuesday 15 November from 8:30 – 9am.
Professor David Moore was appointed Professor in the Department of Nutritional Sciences and Toxicology at theUniversity of California Berkeley in 2020. He studies the diverse functions of nuclear hormone receptors, with a particular focus on their roles in normal and diseased liver and gut. In our interview, he tells us more about his research and his proudest achievements, so far.
Tell us a little about your career path so far
I started my lab at Massachusetts General Hospital and the Harvard Medical School in 1981, then in 1997 I moved to Baylor College of Medicine in Houston TX. I have recently moved to become Professor in the Department of Nutritional Sciences and Toxicology at UC Berkeley, where my research will be focused on the role of nuclear receptors in metabolism and metabolic disease. Since my younger brother has already retired twice, the wisdom of starting a new lab may be questionable, but I am still excited by the prospect. Our studies will continue to investigate the regulation of basic metabolism, dysregulation in metabolic syndrome and diabetes, as well as the impact of nuclear receptors in hepatocellular carcinoma, cholestasis, fibrosis and inflammatory bowel diseases.
I’ve always been interested in gene regulation and came to endocrinology because it provides great systems for studying this central process. This is particularly true for the nuclear hormone receptors that have been the focus of my entire career.
Who were you most inspired by?
There are a number of really great scientists in the nuclear receptor field who have set a very high bar. In a bit earlier generation this includes Bert O’Malley and Pierre Chambon. Closer to my age the list is longer but includes Mitch Lazar, Ron Evans, David Mangelsdorf and Steve Kliewer, and Holly Ingraham. I am happy to consider all of them friends, and apologies to many other friends and colleagues who also deserve mention.
What are you proudest of in your career, so far?
As a personal achievement, I was proud to be elected to the US National Academy of Sciences. As a scientific accomplishment, the fact that our early efforts in the orphan field, along with those of others, led to the discovery of all 48 members of the nuclear receptor superfamily before the human genome sequence was completed, is a great accomplishment. On the other hand, it could be argued that if we had just waited they would have been handed to us on a platter!
How much has your field changed since you started out?
This is an easy question – the explosion of “omics” tools. The human genome is the most obvious example, but there has been a fundamental transition of experimental focus from gene-by-gene or protein-by-protein to the whole system level.
Being able to follow ideas where they lead to yield new insights.
What will you be presenting in your lecture at SfE BES 2021?
I’ll be discussing our latest research on how the liver manages its resources in the presence and absence of food.
Any words of wisdom for aspiring endocrinologists?
Follow your dreams and visions. Pursue the questions that you find the most intriguing, not those that someone else says are more practical!
You can attend Professor David Moore’s Medal Lecture, “Feast and Famine: Nuclear Receptor Control of Liver Energy Balance” on Tuesday 9 November at 08:30 GMT.
Find out more about the scientific programme for SfE BES 2021.
Professor Greet Van den Berghe is the head of the clinical department and laboratory of Intensive Care Medicine at KU Leuven University and its University Hospitals in Belgium. The Leuven Clinical Intensive Care department is a large, tertiary referral centre treating over 3,100 patients per year. She is also Professor of Medicine at KU Leuven and actively researches the endocrinology and metabolism of critical illness. Here she tells about her career, research and how important it is to break boundaries and challenge classical ideas in the pursuit of better patient care.
Tell us a little about your career path After obtaining my medical degree, I trained in anesthesiology and intensive care, then in biostatistics and later completed a PhD in endocrinology. I followed this path so that I could work at the boundaries of several disciplines, which provided an excellent opportunity to build a multidisciplinary research team and to expand on translational research in endocrinology and metabolism of critical illness, from bed to bench and back.
What inspired you into research? When I was a junior attending physician in the intensive care unit (ICU), I observed that long-stay ICU patients, both children and adults, quickly began to look much older than their chronological age. At the same time they showed endocrine and metabolic abnormalities that mimicked certain characteristic of ‘ageing’. I hypothesised that maybe this ‘accelerated ageing’ phenotype of ICU patients could in part be iatrogenic, and if so, may be preventable. These thoughts formed the basis for my PhD research, in which I demonstrated that dopamine infusion, a drug commonly used at the time for haemodynamic and renal support, was causing an iatrogenic suppression of the anterior pituitary with harmful consequences. Based on these findings the practice of infusing dopamine in the ICU was abandoned.
In my postdoctoral research, we went a step further and identified biphasic neuroendocrine and metabolic responses to acute and prolonged critical illness in both patients and animal models. This research clarified many earlier, apparent paradoxes and provided the basis for our later work that focused on the acute and long-term harmful impact of hyperglycemia, the early use of parenteral nutrition and the pathophysiology of the HPA axis response to the stress of critical illness.
What are you proudest of in your career, so far? In 2002, I inherited a very large and well organised clinical intensive care department to chair, upon which I have built research from bed to bench and back again. There was no research in the department when I started, so I had to build everything from scratch. Over the years, this growing symbiosis, between high-level patient care and research, has proved to be very successful. This also allowed me to recruit the best clinicians and scientists who now work effectively together as a very close team.
Together we have made exciting discoveries and we were able to repeatedly close the loop from an original idea triggered by patient care, to basic research in the lab and back to randomized-controlled trials in patients. That is such great fun! So, I am most proud of my team, and grateful to them for making me happy every day!
What do you enjoy most about your work? I enjoy thinking outside the box, creating new ideas by crossing boundaries between classical disciplines, and working with young, enthusiastic physicians and scientists, to generate new knowledge that forms a solid basis for better patient care.
What will you be presenting in your lecture at SfE BES 2021? In my talk, entitled “Re-thinking critical illness induced corticosteroid insufficiency”, I will present novel insights from our recent research on HPA axis changes that occur in response to acute and prolonged critical illness. I will challenge the classical paradigm of stress-induced increased ACTH-driven cortisol production as the basis for increased systemic cortisol availability in severely ill patients. I will also challenge the idea that a short ACTH stimulation test can diagnose failure of this stress response.
To say it with a metaphor: “What you see is not always what you get”.
Any words of wisdom for aspiring endocrinologists? Look further than the boundaries of your own discipline, there is much to be learnt and innovated when you go beyond them!
You can attend Professor Van den Berghe’s Medal Lecture, “Re-thinking critical illness induced corticosteroid insufficiency” on Tuesday 9 November at 18:45.
Dr Julia Prague is a clinical consultant and clinical academic at the Royal Devon and Exeter NHS Trust and University of Exeter. In our interview, she tells us about her clinical practice and research projects, as well as how she thinks endocrine practice will evolve after the COVID-19 pandemic.
Tell us a bit about your current positionand what you enjoy most
As a clinical consultant and clinical academic I split my time almost 50/50 through the week. At the moment, my clinical commitments include outpatient endocrinology, and inpatient endocrinology, diabetes and general medicine. I moved from London to Exeter last year, and one of the big reasons to move was that near 50/50 split between clinical commitments and research. It’s a great balance that gives me time and space, not only to be with the patients, but also to investigate and take forward some of the issues that they bring up in clinic. Forming new collaborations and being in a new unit with new colleagues is pretty exciting too.
Research wise, I’m particularly interested in the menopause through a number of different collaborations. I’m working with the respiratory department on a project looking at lung conditions and sex hormones. Investigating the impact of the menopause in diabetes. I’m also still involved in establishing the role of neurokinin 3 receptor (NK3R) antagonists to treat hot flushes and improve sleep during the menopause.
What got you interested in research on menopause?
Spending hours with the women in our research study of a new treatment for menopausal flushes, and from receiving hundreds of emails from menopausal women wanting to take part. My admiration for them was huge, not least because they so often described themselves as struggling to cope, yet they were the complete opposite of that, meeting endless challenges with amazing fortitude and whilst mostly suffering in silence. To then see them leave misery and suffering behind and find themselves feeling vibrant and human again was rewarding beyond measure.
Furthermore, the majority of women will have menopausal symptoms that impact on all aspects of their daily life, but many will also have co-existing medical conditions before their menopause and these can also be impacted too. Many medical conditions are influenced by the menstrual cycle and that’s an aspect that is under-investigated and I think is really interesting. Inflammatory bowel disease, for example, can fluctuate during the menstrual cycle and Crohn’s disease typically gets better in pregnancy.
Diabetes is also impacted by the menstrual cycle, and it’s the same hormones that are changing during the menopause but this hasn’t been investigated, which is why I’m now interested in this, as this is something patients often report as being a problem for them. I think it’s important to listen to what patients are telling you and then try and investigate why that is, to hopefully find an improved solution for them.
How was your work affected by the COVID-19 pandemic?
I was a Senior Registrar at King’s College Hospital at the height of the first wave, so I became involved in a lot of the management and service re-design work within the diabetes and endocrinology department, including rota management to facilitate re-deployment to general medicine but whilst maintaining a core specialist service and whilst supporting our junior trainees and particularly our international medical graduates who were isolated from their families, and ensuring our patients were supported and aware of sick day rules and had all the medications they needed. Our department was also therefore part of the frontline team. I was the medical registrar on call for the first peak weekend of King’s admissions. Then I got COVID-19 and could not get out of bed/off the sofa for 4 weeks.
I moved to Exeter towards the end of summer 2020 to take up my Consultant job. Since then I have continued to do quite a lot of frontline COVID inpatient medicine. Now we’re involved in recovery and trying to catch up. Many patients couldn’t be seen through the pandemic because resources had to be syphoned off elsewhere.
I never imagined I would interview for my consultant job on Zoom! Moving to a new city, a new department, a new consultant role and a new research role during the pandemic was definitely an interesting twist at such a significant stage of my life and career.
What are you proudest of in your career so far?
My work on menopause and NK3R antagonists – being published in The Lancet was a huge honour, and the potential that this work has to relieve suffering of women is incredible. As a doctor, all you want is to relieve suffering in your patients and this has that opportunity. It’s also given me a platform to continue working in that field and to be invited to speak at international conferences, as well as develop new collaborations.
This drug class are now in phase three studies and it looks like they’re probably going to be marketed from around 2023/2024. This research is still advancing within the pharmaceutical field, butte top-line results coming out continue to show great promise for the therapy. Seeing the NK3R antagonists come to market will be amazing. For me, to have played some part in that will be awesome and to see patients being able to go to clinicians and get that medication prescribed will be great.
There will be far fewer centres doing more complex endocrinology, and the development of this could be guided by some of what we have learnt regarding remote consultations and remote networking during the pandemic.
What do you think are the biggest challenges in endocrinology?
We have to mention COVID recovery, in what was an already overstretched system. However, somewhat linked to that, is the pull of general medicine on our time as endocrinologists. The pandemic has further highlighted this to be an important issue. Hospital inpatient medicine is busy and can’t be cancelled. However, it is essential for recruitment, training, and retention that our specialist time is more protected. The new internal medicine training (IMT) programme will change the number of specialty training years to shorten it, which could have some quite big consequences for the endocrine discipline.
COVID-19 has brought some positives though; it’s highlighted that we can achieve quite a lot remotely with patients using virtual appointments, and some patients prefer fitting their appointments in to their life rather than having to attend the hospital. How this translates going forward though could involve big changes for the specialty.
The Society has become much more inclusive, and far more diverse, with a much broader mix of people, and I think that should really be celebrated and welcomed.
What do you think will be the major changes in the future of endocrinology?
I think there will continue to be a drive for a smaller number of national centres of excellence in endocrinology. There will be far fewer centres doing more complex endocrinology, and the development of this could be guided by some of what we have learnt regarding remote consultations and remote networking during the pandemic. That will be good for patients overall but the downside could be that there will be a smaller number of centres with specialist services, which means that staff may have less involvement in specialist endocrinology. A lot of these changes will be driven by the GIRFT recommendations, which will affect how all services are delivered going forward.
What challenges do you see for your research?
Availability of funding will be critical. COVID has had an impact on available funding but so has Brexit, there’s now a lot of European grants that UK researchers will not be eligible for. Universities have less money because they’ve had fewer students and international students may think differently about studying in the UK post-Brexit and post-pandemic. Charities that fund research have also been hit as many of their fundraising activities were suspended during the COVID restrictions. The Government has a significant financial deficit to address. Availability of research funding was already challenging but it’s going to be even more difficult in the years to come. It’s usually funding that restricts research activity rather than a lack of ideas or collaborations.
How would you like to see the Society develop?
My overwhelming memory of attending my first Society meetings in 2006/2007 is of a lot of senior white men wearing tweed jackets! Now every time I come to Society meetings it’s such a stark change from that. Everything that the Society has done, and is doing, to make itself more reflective of everyone within it is really important. Recruiting the next generation is also a huge part of that, and it is great to also see more focus on this now than then too. The Society has become much more inclusive, and far more diverse, with a much broader mix of people, and I think that should really be celebrated and welcomed.
That level of change takes time and effort and over the years I’ve tried to play some part in helping to make the Society a more different place to the one that I initially knew.
As a Leadership and Development Awardee I was really looking forward to SfE BES 2020 as we were going to be paired with award lecturers, and it is also always a great opportunity to catch up with friends, previous colleagues, and previous as well as potential new collaborators. But of course, that didn’t happen. I’ve just been finding my feet as a new consultant and researcher in a new city but being an Awardee has opened up other opportunities. I’ve been involved in discussions with an external organisation exploring new collaborations and identifying our shared goals and objectives that we could achieve together. I’m sure that being an Awardee has helped me be offered these opportunities.
Who have you been most inspired by?
Prof John Wass, obviously, but I have also been very lucky to have amazing clinical and research mentors. From the literal beginning to the end of my clinical training and beyond (now over 15 years!) with Dr Simon Aylwin at King’s and Dr Roderick Clifton-Bligh in Sydney. I also learnt a lot from Prof Waljit Dhillo whilst doing my PhD at Imperial.
Why do you love endocrinology?
The balance of the acute and long-term follow up of patients, and the importance of making the right diagnosis for patients based on their history, examination and targeted investigation. Many patients with endocrine conditions go undiagnosed or misdiagnosed for a long time, so when you make the right diagnosis and instigate the right treatment, they feel and do so much better and you often see it unfold in front of you. As endocrinologists we are also part of a much wider multidisciplinary team, which is great.
Any words of wisdom for aspiring endocrinologists?
I’ve always tried to be involved with the Society in recruiting the next generation. It’s important that they get to see the ‘real’ endocrinology and diabetes because often, those rotation attachments are mostly inpatient general medicine.
My advice would be to try to get to clinic as much as possible because a lot of our patients are outpatients, and also to go and review specialty patients on the wards when they are admitted. Remember also that there’s lots of different sub-specialties within endocrinology (and diabetes) so there is a place for everyone and an opportunity to be involved in the areas that you find most interesting/rewarding.
Don’t let yourself be put off by the general medicine component or thinking that it’s all diabetic feet! I also always recommend going to SfE BES, it’s a really good platform for meeting other clinicians and scientists involved in the field, and hearing about the patients that we look after. Get involved, come along and see what the specialty really has to offer.
We are keen to reflect the diversity and breadth of our discipline by hearing from members across all backgrounds, career stages, career types and geographical locations, to get a true flavour of the range of views, needs and challenges faced by our Society members.
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 inneuroendocrine 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.
Meet Simon Pearce, Professor of Endocrinology at Newcastle University and Programme Secretary for SfE BES 2017, in Harrogate, 6-8 November. We caught up with him to find out more about his work and to discover his upcoming highlights and top tips for the conference.
Q: Tell us a little about your career path and endocrine interests
I qualified in medicine at the Newcastle University, completed my postgraduate education at the Royal Postgraduate Medical School in Hammersmith, Brigham & Women’s Hospital in Boston and as a Lecturer in Newcastle. I was appointed Senior Lecturer in Endocrinology in 2001 at Newcastle University and became Professor in 2007.
My main research area is the treatment for autoimmune thyroid diseases and Addison’s disease. I have published around 150 papers over the last 20 years spanning molecular endocrinology, clinical trials and guideline papers.
Q: Tell us a little about your role as SfE Programme Secretary
As Programme Secretary I organise the scientific programme for the annual conference. It’s a great privilege to be able to choose the speakers that I want to learn from. My assumption is that if I am interested in the topic, then it will interest others too.
2016 was my first year as programme secretary and the informal feedback about the quality of the symposia and meet the expert sessions as the meeting progressed was great. I was very happy on the last day when it was all over though, with no significant hitches.
Q: What do you think are the programme highlights at SfE BES 2017?
There is a very strong programme on several subjects including calcium and bone, thyroid, and female reproductive endocrinology. Following the success of last year’s thyroid masterclass, we have scheduled a bone masterclass with two internationally respected experts on osteoporosis, a clinical management symposium on hyper- and hypo-calcaemia and a session on steroids and bone.
The meet the expert sessions on opiate-induced hypopituitarism, hyperthyroidism in pregnancy and next-generation DNA sequencing promise to keep you up to date on the latest advances in these important and fast-moving areas.
We also welcome more than 20 overseas speakers, including cutting edge plenary lectures from some giants in our field, Teresa Woodruff, Andrew Arnold and Martin Schlumberger. Home-grown highlights will also include two well-known members of our Society, Andrew Hattersley and Julia Buckingham, who never fail to both entertain and inform.
Q: What are you particularly looking forward to?
I always enjoy the plenary lectures, and Andrew Hattersley has been an inspirational role model for me; translating the highest quality laboratory science to change clinical practice and improve patient outcomes. So I think his talk will be a highlight.
Q: Do you have some words of wisdom for anyone attending SfE BES for the first time?
Have a good look at the programme at a glance page and plan your most interesting sessions carefully. I receive frequent comments that there is too much going on at the same time during the meeting and people would like to split themselves in two. My advice is go to the session that you know least about, as you stand to learn the most from this, even if it feels slightly outside your normal ‘comfort zone’.
Q: What do you think will be the next major breakthrough in endocrinology?
It’s clear that there is a lot of pharma work on small molecules that target several receptors at the same time to modulate appetite and metabolic phenotypes. I am also excited that during the next 10 years we may see new treatments for hyperthyroidism; the first advance since the early 1950s.
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.
This year, I was lucky enough to attend my first parliamentary links day. The largest science event in the Houses of Parliament, this day is held to promote dialogue between parliament and the scientific community. Given the vote to leave the EU less than a week earlier, it couldn’t have been a more interesting time to attend!
The scientific community directly benefit from the EU in terms of funding, collaboration and free movement of people. It was therefore no surprise that this year’s event saw the biggest attendance in history. The event, opened by John Bercow MP (Speaker of the House of Commons), involved opening remarks from Jo Johnson (Minister for Universities and Science) and Nicola Blackwood (Chair of the Science and Technology Select Committee). Two panels then followed, and then final speeches were given by Lord O’Neill of Gately, Sir Venki Ramakrishnan, and Stephen Metcalfe MP. Bewildered scientists filled the room, all anxious about their now uncertain future, and all speakers tried their best to reassure us.
‘Nothing has changed overnight in legal terms’ said Jo Johnson. MPs agreed that we have a strong country with a resilient history, and are able to pull through. Our science in particular they say is world class, and this can be used to help in our recovery. Many speakers told of reassurance from abroad, recognising the work we do and that they want to continue collaborating. These academic networks can therefore provide an alternative to the political networks, and help to smooth waters. So the message was one of hope and determination, despite the disappointment.
All emphasised that we now need to shout loud to ensure that science is prominent in the negotiations and in particular that the government maintain our overall investment in science. MPs assured us that they will do their best to fight for these things, and they said that we also need to send out the message to connections and networks across the world, that despite this decision Britain is a willing collaborator and welcoming society. Finally, they asked us to think about what we can learn. Although leaving the EU would clearly be bad for science, half of the public still responded with the leave vote. This suggests that science is not important to them, so what can we do now to convince people that science is worth investing in?
I will always remember this day at such an important time in British history. After all the hope given I look forward to seeing what the future holds for UK science!
Amber Abernethie is in the second year of her PhD in Cardiovascular Biology. She is based at the Queens Medical Research Centre (University of Edinburgh) but is originally from Cleethorpes, England.
Following the referendum result on the UK’s membership of the European Union (EU) the Society for Endocrinology urges the UK government to ensure that free movement of students, researchers and clinicians between the UK and other EU countries and full access to, and participation in, the EU research infrastructure is preserved. We strongly believe that the free movement of labour is essential to the delivery of care within the National Health Service (NHS) and to ensure that the UK continues to be a world leader in international scientific research. The full statement is available on our website.
The Society for Endocrinology provides early-career grants to support its members in a number of ways. In this article, Kerry McLaughlin explains how the grant helped her search for an elusive autoantigen, which made a splash on the BBC news page earlier this year.
People who have type-1 diabetes lose the ability to control blood sugar levels because of the destruction of insulin-producing cells in their Islets of Langerhans. We know this is because the immune response targets four specific proteins (known as autoantigens), and while the fifth major autoantigen has been known to exist for over 20 years its identity was unknown.
Technical limitations at the time made it impossible to identify the fifth autoantigen, but we used a combination of biochemical techniques alongside high-tech mass spectrometry to discover that this fifth major autoantigen was tetraspanin-7, at last providing a complete picture of the immune targets in type-1 diabetes.
This discovery can now be used to help identify those at risk of future disease development through the detection of antibodies to tetraspanin-7, and to further research into strategies aimed at blocking the immune response to the major autoantigens in order to prevent the disease altogether.
This research came about as a result of work we were doing with a separate autoantigen (IA-2). My postdoctoral supervisor, Dr Michael Christie, was involved in earlier efforts to identify the fifth major autoantigen, and we realised that we could apply the technology developed for IA-2 for this purpose.
This was where the Early Career Grant from the Society for Endocrinology came in and provided some much needed resource to kick-start the project. While it took a little bit more time and effort to finally identify tetraspanin-7 as our elusive fifth autoantigen, this early funding was instrumental to the project’s successful completion.
I have since been awarded a 3-year fellowship by JDRF to continue my research into tetraspanin-7 in the laboratory of Professor Patrik Rorsman FRS, FMedSci at the University of Oxford. We published our study in Diabetes, and it was covered in the mainstream media by the BBC, at one point trending in the top 10 news articles, as well as by the Huffington Post. It was great to have the opportunity to share our research with the wider public, and I was very motivated to see how interested people were in hearing about scientific advances.
For young researchers, getting enough preliminary data to put together a competitive grant application for a major funding body can be tricky. The Early Career Grant from the Society for Endocrinology provides postdocs with the opportunity to explore a new avenue of research and can be used to provide that all-important first proof-of-concept.
The second advantage to this scheme is that it gives early-stage researchers a chance to go through the process of preparing an application for funding as well as managing an award, but on a much smaller scale and without the heavy administrative burden of larger grants. I would certainly recommend the scheme to those keen to take the first step towards an independent career in research.
Kerry McLaughlin, originally from Cape Town, South Africa, was awarded her PhD in Immunology from King’s College London in collaboration with The Pirbright Institute. She then spent six years as a postdoc in the laboratory of Dr Michael Christie at King’s College London before taking up a JDRF fellowship at the University of Oxford in 2016.
For details on how to apply for our Early Career Grant, visit our website. The next deadline for applications is 27 November 2016.
The annual Society conference, SfE BES, takes place this year in Brighton on 7-9 November 2016. It’s a great chance to network with colleagues, showcase your work and explore new research in your area of endocrinology. Our programme of events is varied yet specific – bringing together the best of basic science, clinical investigation and clinical practice, you have the chance to expand your horizons into other parts of the field whilst also attending those lectures which are really specific to you.
The submission system for abstracts is open until midnight on Wednesday 22nd June – so you have more than enough time to polish your final abstract and send it along. It’s not just a chance to show your colleagues across the whole field of endocrinology what you’ve been working on – it’s a chance to tell them why what you’ve been working on is important.
Last year at SfE BES, a great programme highlight was a session entitled ‘Evolving model systems for complex tissues’, which was chaired by Kevin Doherty and Shareen Forbes. In the ’90s, manipulation of human embryonic stem cells (hESCs) was something of a new thing. It was anticipated that the ability to grow human tissues in culture using hESCs would provide incredible model systems for drug development, toxicity testing and cell therapy.
However, it wasn’t until 2005 that reliable markers had been developed and a significant number of important signalling pathways had been elucidated in the path to differentiation. By this point, some ten years later, finally a tool box existed for nearly every tissue type. This lead to some of the first clinical trials, using pluripotent cells to treat age-related macular degeneration. However, liver disease, diabetes and neurodegeneration were still elusive and challenging goals.
By 2014, fully functional human beta cells has been generated, and they took only 45 days and 7 stages in culture. This was a hugely exciting moment for diabetologists and researchers across the world. But then, of course, the question sprang up: could they be used as a source of islet cells for replantation? Or would they merely serve as an invaluable model?
At Kevin and Shareen’s BES session, they gave a detailed overview of both the background to the field of complex tissue model systems, and the current state of basic science and clinical research, highlighting very recent advances, and discussing the potential future.
The stem cell field continues to expand rapidly. 2016 has already been the year that Chinese scientists grew functioning mouse spermatozoa from skin cells – these went on to fertilise egg which developed into embryos and grew to successful progeny. What will the second half of 2016 bring?
With over 1000 delegates, 100 abstract lectures, 10 plenary lectures, and an evening of awards and prizes, SfE BES is the best place for you to spread the word on your research, and meet the colleagues that you want to work with in future. Your lecture might be the one were talking about all the way into June 2017.