Meet the Endocrinologist: Matthew Simmonds, expert in pancreatic transplant genomics

Meet the Endocrinologist: Meet Dr Matthew Simmonds a Senior Lecturer in Biomedical Science at the University of Lincoln. His research is focused on the genetics of pancreatic transplant function and he will be presenting at the Early Career session at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, he tells us more about his work and what he is looking forward to at the SfE BES 2018 conference.

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

I am a Senior Lecturer at the University of Lincoln where I have been now for just over two years.  My research career has revolved around trying to identify genetic contributors to a series of autoimmune endocrine diseases including autoimmune thyroid disease and type-1 diabetes.  My current research is specifically focused on looking at genetic predictors of long-term pancreas transplant function in people with severe type 1 diabetes.

What inspired you in to this field?

The immune system is amazing and without it we would never have survived and evolved on this earth. What I find so interesting about the autoimmune endocrine diseases is how the immune system, which is meant to protect us, actually starts to attack parts of the body leading to changes in how the endocrine system works.  I am passionate about understanding how disease pathways are triggered/progress and how we can use these insights to inform better treatments for people with these different conditions.

What do you think are the biggest challenges in your field of research?

I think the major challenge within pancreas transplantation is both the number of donor organs available for transplantation into people with severe type-1 diabetes and trying to ensure that the transplanted organ remains functional throughout the recipient’s life to ensure the benefits these transplants provide, of retuning insulin production and halting/reversing secondary diabetes related complication in that person, remain for as long as possible.

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

I think both the advances being made in using induced pluripotent stem cells, combined with gene editing, to create new beta cells, will provide unparalleled new opportunities for transplantation purposes. Combined with the decreased costs around genome and other proteomic screening for patients and our increased understanding of how genetic variation impact upon autoimmunity and transplant success this will give us new understanding of disease progression and provide better individual tailoring of therapeutics.

What will you be doing at SfE BES 2018 in Glasgow?

Well as you have asked – nothing like a bit of shameless plugging – I will be doing a talk on the Tuesday as part of the Early Careers session ‘Navigating the Academic Pathway’.  My talk is entitled ‘The lectureship route’ where I will be providing some insights into this career pathway, the challenges and benefits of this route and some tips on how to be get such a position.

What are you looking forward to at this year’s conference?

I think as an early career researcher I loved going to conferences to be able to present my work and network with others working in the field – which is the same reason I enjoy attending conferences to this day. Whilst there are lots of fantastic talks, plenaries and other sessions throughout the conference with something to suit everyone’s research interests, one thing I would suggest to early career researchers is to take time to speak to other early career researchers at the poster sessions and after their talks.  You would be surprised how much you have in common with other researchers and how random conversations at conferences can lead to new collaborations and possibly job offers in the future.

Who do you most admire and why?

 I have been really lucky to have worked with some of the most amazing researchers in diabetes and endocrinology throughout my career so far – both in the centres I have worked and through numerous collaborations. I have been very lucky to have some amazing mentors throughout the years, and think that whatever stage in your career you are at it is important to keep listening, learning and being inspired by researchers at every level.

What words of wisdom do you have for someone starting out in research?

These type of questions always make me feel old.  Joking aside, I think the best advice I can give to any early career researcher is to think about where you want your career to go but don’t be so rigid in your approach that you may miss out on some unexpected opportunities that come your way. Also listen to your gut feeling about career decisions.  Whilst is it perfectly normal to be scared to take on new challenges be it new techniques, moving into different project areas or new jobs, sometimes you instantly know if something is a good or a bad move. From my own experience I have learnt that sometimes saying no to something that is not right for you is as important as the opportunities you say yes to.

You can hear Dr Simmonds presentation, “The lectureship route” on Tuesday 20 November, as part of the Early Career: Navigating the Academic Pathway session at 16:00-17:30. Find out more about the scientific programme for SfE BES 2018.

 

 

Meet the Endocrinologist: Jeremy Turner, expert in bone and calcium endocrinology

Prof Jeremy Turner is a consultant endocrinologist at Norfolk and Norwich University Hospitals NHS Foundation Trust. He has a particular clinical interest in calcium and metabolic bone disorders and is a convenor of the Society’s Bone and Calcium Endocrine Network.

What inspired you into endocrinology, and bone and calcium in particular?

I was fortunate enough to undertake my early postgraduate training in endocrinology at the (then) Royal Post Graduate Medical School/Hammersmith Hospital in the mid-1990s, where I worked with some inspirational colleagues in the bone and calcium field. I then went on to undertake an MRC clinical training fellowship in Raj Thakker’s lab in Oxford. The latter experience firmly cemented the place of calcium and bone endocrinology in my endocrine repertoire.

Can you tell us a little about your current work?

I have been consultant endocrinologist for the last 9 years in Norwich and was more recently promoted to honorary professor at the Norwich Medical School. I run the clinical metabolic bone/calcium service in Norwich with my great friend and colleague Professor Bill Fraser. We have established a good reputation for our clinical service and referrals come in from far and wide. We provide over 120 consultant delivered lists per annum and have succeeded in getting Norwich recognised as a Paget’s Association Centre of Excellence.

Historically, bone and calcium disorders have been somewhat “Cinderella” conditions in the wider context of endocrine services and I particularly enjoy advocating for this population of patients and developing services in this area. I am medical advisor to Hypopara UK and of course promote the charity and its work to our large population of hypoparathyroid patients. I have led the writing of a number of clinical guidelines including a post-operative hypocalcaemia avoidance and management guideline, have developed services such as a one-stop osteoporosis clinic and am currently working with colleagues in Cambridge to set up a rare bone disease network in the East of England. Naturally, the achievement I am proudest of is being appointed as a network convenor for the Bone and Calcium Endocrine Network of the Society for Endocrinology!

Over the last decade or so, what do you think have been the most useful/impactful advances in bone and calcium?

As a pure endocrinologist, the single most exciting advance has been the arrival of recombinant human parathyroid hormone (PTH) for the treatment of hypoparathyroidism. Finally, clinical endocrinologists now have a “full set” of replacement hormones to use in hormone deficiency states and this day has been a long time coming. However, no answer to this question would be complete without reference to the arrival of the many new therapies for osteoporosis and perhaps, as importantly, the expansion in understanding of treatment of osteoporosis that has occurred in recent years. This has included appreciation of risks of treatments as well as benefits, how to use the different therapies, where they fit in relative to each other, the growing use of bone markers, fracture risk calculators and so on – all of which are driving more nuanced, considered and targeted clinical approaches to treatment of osteoporosis.

What do you think are the biggest challenges faced by endocrinologists?

In my opinion, the biggest challenge faced by all endocrinologists has to be management of remorselessly growing demand. The population is expanding and ageing and at the same time more treatments are available across endocrinology. Awareness is growing amongst patients and general practitioners and thus referral rates are rising. This is a good thing, it means that our specialty is able to help more and more people for whom perhaps help was not always available in the past and also means that the place of endocrinology in clinical medicine as a whole is better recognised and appreciated. However, it is up to us to manage this demand, find new ways to see and treat as many people as possible and to modernise aspects of our practice. Not changing how we work is probably not an option!

Are there any controversies in bone and calcium endocrinology?

Of course there are many controversies but one of the greatest at the moment is probably the recent recognition of the end-of-treatment effect of anti-RANK ligand therapy whereby fracture rates may rise quite fast in some patients upon withdrawal of this therapy. This is a very pressing clinical challenge as numbers on this exciting and novel treatment are quite large, we have been using this for a period of time that means that some are already arriving at what was originally intended to be the end of treatment but now we know that simply stopping the treatment is probably not the best option for many patients. At the same time, there is a relative lack of evidence base to inform us with regard to what we should be doing next. While it is helpful that some guidance is beginning to emerge, this is largely based on expert opinion and it will be very interesting to see how this controversy unfolds over the next few years.

What do you enjoy about being an Endocrine Network convenor?

 So far it is early days but I am enjoying working with my co-convenor (Caroline Gorvin), with colleagues in the society and am looking forward to playing my own very small part in further raising the profile of bone and calcium medicine and research within endocrinology.

Do you have any words of wisdom for aspiring endocrinologists?

Yes, this is perhaps the easiest question; Enjoy your endocrinology! If you are enjoying your clinical practice you will be happy and more importantly your patients will be happy, correctly diagnosed and correctly treated.

 

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.

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

Meet the Endocrinologist: Petros Perros, thyroid disease expert

Dr Petros Perros is Honorary Clinical Senior Lecturer at Newcastle University, and a consultant in endocrinology at Newcastle Hospitals. His clinical and research interests focus on the study of thyroid disease, and he is a convenor of the Society’s Thyroid Network.

What inspired you into medicine and why did you focus on thyroid disease?

I got inspired into medicine through observing the impact of successful treatments on people’s lives and the misery brought onto those who are incurable. Appreciating that science was the key to solving those problems was my main motivator to pursue a career in medicine.

As a student, I was attracted by the relevance of endocrinology in every system and organ, and the beauty and elegance that was revealed from studying it. The frequency of thyroid conditions and the interests of my mentors contributed towards my focusing in this area. However, I can also recall how impressed I was when I read about the discovery of the therapeutic role of radioiodine in hyperthyroidism and thyroid cancer: a perfect marriage of physics and clinical medicine leading to the first “magic bullet” treatment in medicine.

Can you tell us a little about your work?

Graves’ orbitopathy (GO), also known as thyroid eye disease (TED), has been the focus of my clinical and academic interests. This has enabled me to work closely with colleagues in other disciplines, which has been immensely rewarding.

There are rapid advances in understanding the pathophysiology of GO, and a plethora of biologics are already available and beginning to be used with impressive results. Besides the high tech available, the realisation that low cost, conventional interventions can influence the course of this disease has also made the topic of implementation very interesting and challenging. Now is a fascinating time for people working in this area.

What do you think have been the most impactful advances in thyroid clinical practice and research?

For thyroid research, one of the most relevant outcomes of the Human Genome Atlas has been the demonstration that the commonest thyroid cancer (papillary) has one of the simplest genetic mutational repertoires, so the scope for therapeutic interventions to silence driver mutations is a realistic expectation. I anticipate that prognostic evaluations and novel thyroid cancer treatments will reach the clinical arena in the next decade as a direct result of this.

What will be the next breakthrough for treatment or diagnosis of thyroid conditions?

In my opinion, targeted therapies in advanced thyroid cancer are at the top of the list. Immunotherapies for autoimmune thyroid disease are also emerging. In basic research, we can expect to learn more about the application of regenerative medicine in thyroidology, and we will hear a lot more about the role of thyroid hormones in dementia.

What are the biggest challenges faced by your clinical specialty?

We need to reverse the tide of unnecessary investigations and treatments relating to endocrinology, as this has an enormous negative impact on patient care and wastes large amounts of resources. Another challenge is attracting the brightest doctors and scientists to our discipline, and strengthening the links between endocrinology as a clinical specialty and as a scientific area.

Are there any controversies in your practice area?

Some decades ago, we thought that we had solved the problem of thyroid hormone replacement. Yet, some patients remain dissatisfied, seek alternatives, and have recently launched a war against “conventional” endocrinologists. Unfortunately this is exacerbated by self-appointed experts from the dark alleys of alternative medicine, who exploit human suffering and desperation. However, on the bright side of things, this controversy has raised some valid research questions that are answerable by scientific investigation, and the new knowledge gained from it will help resolve some of these issues.

What do you enjoy about being a Network convenor?

I particularly enjoy the interaction with colleagues, especially the young ones. Endocrine networks have a great potential for bringing individuals with similar interests together and promoting research in endocrinology.

Do you have any words of wisdom for aspiring endocrinologists?

If you find endocrinology intriguing, delve into it and have a taste. Don’t be put off if it seems too complicated – it only means there is more to discover. Endocrinology is a great specialty full of surprises and rewards.

Find out more about the Society’s Endocrine Networks, and how they can provide a platform for knowledge exchange in your area of focus.

Meet the Endocrinologist: Dr Barbara McGowan, expert in obesity and bariatric surgery

Barbara McGowan is a consultant in diabetes and endocrinology at Guy’s and St Thomas’ in London, and a convenor of the Society’s Metabolic and Obesity Endocrine Network. Dr McGowan leads the obesity bariatric service at the hospital and her areas of research interest include gut hormones and remission of type 2 diabetes post-bariatric surgery.

What inspired you into endocrinology?

My initial biochemistry degree was inspired by a wonderful chemistry teacher. I had considered medicine at that time but the thought of a further five years in higher education was enough to suppress those feelings. I then tried my hand at selling my soul to the city and five years as an investment banker was enough to rekindle my spirit and courage to go to medical school. My love for molecules and metabolism made endocrinology an easy choice for me. I was lucky enough to stumble across Prof Meeran and Prof Bloom during my SHO years, who steered me towards a PhD in gut hormones and appetite control, which was supported by an MRC clinical fellowship. In 2009 I took a consultant post at Guy’s & St Thomas’ where I was tasked with developing a leading obesity service from scratch.

Tell us a little about your current clinical work

My work involves management of general and complex endocrinology, with a focus on hereditary endocrine disorders such as SDH disease and multiple endocrine neoplasia. As a lead for the medical obesity service, I also run a Tier 3/Tier 4 obesity service. My clinical research involves the running of several clinical trials on pharmacotherapy and metabolic surgery for the treatment of obesity. I am most excited about trying to understand mechanisms for weight loss and remission of type-2 diabetes post-bariatric surgery.

What do you think have been the most impactful advances in obesity and metabolism clinical practice?

From a clinical point of view, with the exception of metabolic surgery, we have had very little in terms of clinical advances for the treatment of obesity, which is quite surprising given that we have an epidemic of this disease. We have medication coming through but this is still not available in the NHS.

What do you think will be the next big breakthrough for treatment of obesity?

I am hoping that we will soon have much more effective pharmacological treatments that will include more powerful GLP-1 agonists and gut hormone combination therapies, to replicate outcomes from bariatric surgery, but without the surgery. The aspiration is to have better molecular markers that will help us to select patients likely to respond to different therapies.

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

Attracting high calibre trainees is big challenge. Endocrinology used to be considered an academic specialty, however service provision in NHS Trusts has become a burden that has detracted from the specialty. Furthermore, physicians wishing to pursue an academic career face funding challenges.

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

Stigma regarding obesity is still rife, we need to educate the public, media and healthcare professionals and recognize obesity as a chronic disease. Until such time, prevention and treatment of obesity is unlikely to be prioritised.

What do you enjoy about being a Network convenor?

As a convenor, I am able to push the obesity agenda to help ensure it is well represented at SfE meetings. I was able to set up an annual Obesity Update conference at the Royal College of Physicians, and now run by Bioscientifica. The Network makes you part of an obesity family and allows like-minded people to get together and collaborate. Recently, I was able to use the Network to ask for opinion and support as to whether ‘Obesity should be recognized as a disease’. I would urge all members interested in obesity to join the network.

Do you have any words of wisdom for aspiring endocrinologists?

Endocrinology is a wonderful specialty, it spans many important organs and provides a diagnostic challenge for disease management. Do not be put off by the uncertainties and go for it! Speak to your mentors, friends and colleagues for advice, it is a friendly community. And for those interested in obesity as a specialty, sign up to the Network and I look forward to speaking to you!

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.

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

 

 

 

Meet the Endocrinologist: Prof Kevin Murphy, expert in central control of metabolism

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.

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

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

Scott MacKenzie is a lecturer at the Institute of Cardiovascular and Medical Sciences at the University of Glasgow. Dr MacKenzie’s research focuses on adrenocortical production of the steroid hormones, aldosterone and cortisol, and investigates how genetic variability can affects their involvement in causing high blood pressure. In this interview, he tells us more about his research, career path and his role as an Adrenal and Cardiovascular Network convenor.

What inspired you into endocrinology, and why adrenocortical research in particular?

I got into endocrine research by chance. I was studying for an undergraduate degree in genetics at the University of Glasgow in the mid-90s and a lecturer happened to mention that any students interested in a summer research project should go and see John Connell. Everything came from that. Professor Connell, alongside Robert Fraser and Eleanor Davies, was particularly interested in aldosterone secretion by the adrenal gland and the genes that regulated it. At that time, there was also emerging evidence that other tissues including the brain were making aldosterone, so I was set to work on that through a Society for Endocrinology Summer Studentship. Unfortunately, the 8-week project went extremely smoothly, generating some nice data and giving me completely unrealistic expectations of scientific research! On the basis of this, I was then offered a PhD project in the same lab devoted to investigating extra-adrenal production of aldosterone in the rodent brain. I continued researching in this area, but over the years, I came to the conclusion that extra-adrenal production of aldosterone is unlikely to be of any physiological importance in humans. Fortunately, new questions were starting to be asked around adrenal secretion of aldosterone and I was able to apply the methods I had developed to that area. Now I am involved in projects that cover several aspects of this, with particular interest in how secretion can become dysregulated or excessive, as in primary aldosteronism (PA).

Tell us a little more about your current research?

I’m currently involved in various projects examining aspects of aldosterone secretion, which I think is an interesting and important field of endocrinology that has an impact on the cardiovascular health of large sections of the population. My current work includes aldosterone regulation by microRNA, analysis of common genetic polymorphisms that might predispose large sections of the population to PA (and therefore hypertension), and the identification of circulating biomarkers that might aid in the earlier and more accurate diagnosis of different forms of endocrine hypertension. The things I tend to be most proud of are the little bits of problem solving that arise in the course of lab work. I was quite pleased with a slightly obscure method I developed to confirm the unequal expression of two different forms of the highly similar CYP11B1 and CYP11B2 genes.

What do you think will be the next big or important breakthrough in adrenocortical research?

The discovery that the majority of aldosterone-producing adenomas contain mutations at one of just a few key genes encoding ion channels was really a big breakthrough that advanced our understanding of the pathophysiology underlying the majority of PA cases. At the same time, improvements in diagnostic testing for PA are revealing it to be far more common than we had previously thought. I think this will lead to a redefinition of PA to some extent, as we identify mechanisms that result in aldosterone hypersecretion under certain environmental circumstances or in certain sections of the population who are genetically predisposed to respond in this manner. Ultimately, this could result in better diagnosis and more targeted treatment for endocrine-related hypertension.

I’m currently very interested in the impact of environmental and physical stress on aldosterone secretion. The hypothalamic-pituitary-adrenal axis has long been thought to regulate aldosterone secretion in a very limited manner, but recent clinical studies suggest a sizeable minority of hypertensive individuals react to stress by producing high levels of aldosterone. Understanding what predisposes these people to respond in this manner is, I believe, of great importance and could have major implications for how we react to stressful situations in everyday life and its impact on our cardiovascular health.

What do you think are the biggest challenges faced by academic research?

I think the greatest challenge in current scientific research doesn’t apply to any one field but to us all. That is how we ensure that young researchers­­ coming through – particularly basic scientists – have a viable and stable career structure that enables them to progress and thrive in an academic environment. A lot of time, money and training is being invested in these people, but too many are being lost to science as they become disenchanted by successive short-term contracts and the uncertainty surrounding a career in scientific research. I think it is incumbent on older scientists to recognise just how much the career prospects and funding structures have altered in recent years, and to use whatever influence we have to push for greater early career support at institutional and national levels.

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

There are certainly controversial areas in my field; some may argue with my opinion that extra-adrenal aldosterone production in humans is of no importance. Others (if the comments on my recent grant proposal are anything to go by) will disagree with my assertion that stress is an important factor in aldosterone secretion. But, ultimately, any scientific disputes will be resolved as they have always been: by well-designed and well-executed experimental study.

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

I think that Endocrine Networks have tremendous potential to provide opportunities for researchers, particularly those in their early careers, by enabling them to gain supportive and informed advice from more senior members. I hope we are able to build a vibrant online community that is complemented by ‘real-life’ meetings, such as the Research Incubators at the SfE BES 2017 conference, which proved an excellent forum for researchers to get feedback on projects under development. Ultimately, the success of these initiatives depends on its participants, so I would urge all members in relevant areas of research to sign up to a network and get involved.

Do you have any words of wisdom for aspiring endocrinology researchers?

Although I think opportunities are harder to come by now than they were in ‘my day’, young researchers can still distinguish themselves from their peers in the same ways. That means taking every opportunity to make themselves known to prospective employers and supervisors (the dreaded ‘networking’) while at the same time not being too discouraged by the high number of rejections that almost inevitably follow. It also means exploiting opportunities that organisations like the Society for Endocrinology make available to them, such as Travel Grants, Early Career Grants and Career Development Workshops. Applying for these or getting involved with the Networks or the Early Career Steering Group can be an excellent way to develop your research and get your name known in endocrine circles.

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Are there any major controversies in your practice area?

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

What is the most unusual part of your work?

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

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

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

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

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

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

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.

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

 

 

Meet the Endocrinologist: Professor Thakker, endocrine neoplasia expert

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The networks enable members to discuss and find solutions to challenges within their specialist field.

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