Meet the Endocrinologist: Joseph Takahashi, expert on the genetic and molecular basis of circadian rhythms

Meet Joseph Takahashi, Professor of Neuroscience at the Howard Hughes Medical Institute at UT Southwestern Medical Centre. His research focuses on the genetic and molecular basis of the circadian clock in mammals. He has been awarded the SfE Transatlantic Medal and will be delivering his Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, he tells us more about his career, research 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’m an Investigator in the Howard Hughes Medical Institute, and Professor and Chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center in Dallas, Texas. My lab studies the genetic and molecular basis of the circadian clock in mammals. More broadly we are interested in the genetic basis of behavior. My lab is known for discovering the first circadian gene in mammals known as the Clock gene.

One of the initial surprises from cloning the mammalian clock genes was that they are ubiquitously expressed. This eventually led to the discovery that the circadian clock is cell autonomous and that virtually every cell in the body has the capacity for circadian oscillation. Thus, all of our major organ systems contain intrinsic circadian oscillators. This has led to a revolution in studies aimed at understanding the role of clocks in peripheral tissues as well as studies focused on understanding the systems level organisation of the multiple clocks in the body. The core circadian molecular pathway regulates thousands of genes in mammals, and this has led to the discovery of direct molecular links to a myriad of molecular, cellular and physiological pathways. These include direct links to endocrinology, metabolism, immune function, cell growth and cancer.

Can you tell us about your career path, and what you are most proud of?

I have been incredibly fortunate to have had great mentors and colleagues as well as research institutions and funding agencies that have supported me throughout my career.  In college, I was interested in biology, but did not know what careers one could pursue except for med school. Later I had the good fortune to do an independent research project and learned that one could go to graduate school in biology(!). That was the beginning of my research career.  I took a post-baccalaureate year to work with Patricia DeCoursey, one of the pioneers in mammalian circadian rhythms, and then went to work with Michael Menaker for graduate studies. Menaker was the perfect mentor for me. He had a free and open lab environment that encouraged creativity, independence and scale and automation. We pioneered long-term ex vivo culture of tissues that contained and expressed circadian rhythms in the late 1970’s. These initial forays continue to pay off decades later as the entire circadian field uses large-scale data collection, automation and long-term in vitro circadian models.

After graduate school, I did a 2-year post doc with Martin Zatz at the NIH where we worked on the pharmacology circadian rhythms in the chick pineal in vitro.  I was then recruited to Northwestern University by Fred Turek. As an independent faculty member at Northwestern, my lab focused on reductionist dissection of the circadian oscillator in the chick pineal.  In addition to pharmacology, we worked on the biochemistry of various circadian pathways in the pineal.  However, eventually we were stymied, and my interest in the molecular biology and genetics of circadian rhythms was growing.  We knew that molecules and genes had to be important for mammalian circadian rhythms, but how to get there?  That was the beginning of my ‘second career’ as a geneticist.  Ironically as an undergraduate, I was not very interested in molecular biology or genetics (I was interested in animal behavior), but luckily I ‘had’ to take these courses.

In 1990, Larry Pinto, Fred Turek and I decided to use mouse genetics to try to find circadian rhythm mutants. We collaborated with William Dove at the University of Wisconsin-Madison, and Martha Vitaterna conducted our first screen of mice that were ENU mutagenised in the Dove lab.  In our first screen, we isolated the Clock mutant mouse which has a 28-hour period length and a loss-of-rhythm phenotype in circadian activity.  This mutant mouse then provided the means to identify the Clock gene by positional cloning. The isolation of the Clock mutant and the positional cloning of gene was the crowning achievement of my lab.

What are you presenting in your Medal Lecture at SfE BES 2018?

I plan on giving an historical account of our forward genetic approach to finding clock genes in mammals. The effort to clone Clock was massive.  Ten members of my lab worked together as a team for three years to complete the project. In the 1990’s there was no genome sequence. The Clock gene turned out to be huge: it had 24 exons and covered over 90 kB of genomic DNA. Then I will discuss more recent molecular and genomic analyses of the circadian clock gene network. Finally, I will describe our new work on the importance of time and caloric restriction for aging and longevity.

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

I am very much looking forward to seeing all the advances in the field of endocrinology as well as the plenary lectures.

What do you think are the biggest challenges in research right now?

It is of paramount importance to support research in basic science. It is very important to translate these basic science discoveries, but one must remember where these advances had their beginnings.  It is impossible to predict new discoveries and how they will impact medicine in the future.

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

Many important breakthroughs in the circadian field will be their connections to all aspects of cell biology, cancer and metabolism. New views of metabolism and longevity are already being linked to circadian biology.

What do you enjoy most about your work?

I love the fact that we are supported to pursue knowledge and discovery of biological systems.  Making scientific discoveries is like a treasure hunt for adults.  It never gets old, and one discovery always opens the door to countless new questions.  Also, as an academic, we have intellectual freedom that is rare in other professions.

Who do you most admire professionally?

My role models have been: Seymour Benzer at CalTech, who pioneered genetic approaches to complex behaviors; Eric Kandel at Columbia, whose systematic and scholarly approach to understanding learning and memory in simple model systems was fundamental; and Denis Baylor at Stanford, whose biophysical analysis of phototransduction was a thing of beauty.

Any words of wisdom for aspiring researchers out there?

My mantra is:  Always begin with first principles. What I mean by this is that you must understand what you are doing. To an electrophysiologist or biophysicist this is self-evident. But in today’s world of molecular biology and informatics, the kits that you use in the lab and the computer programs that you employ are frequently applied without a fundamental understanding what they are doing and how they work.

 

You can hear Professor Takahashi’s SfE Transatlantic Medal Lecture, “Circadian Clock Genes and the Transcriptional Architecture of the Clock Mechanism” on Monday 19 November, in the Lomond Auditorium at 18:00. Find out more about the scientific programme for SfE BES 2018.

Meet the Endocrinologist: Stafford Lightman, expert on regulation of the hypothalamo-pituitary-adrenal axis

Meet Stafford Lightman, Professor of Medicine at the University of Bristol. His research focuses on understanding the role of the hypothalamo-pituitary-adrenal (HPA) axis in health and disease, and in particular its interface with stress and circadian rhythms and its effects mediated through glucocorticoid signalling. He has been awarded the SfE Medal and will be delivering his Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, he tells us more about his career, research and what he is looking forward to at the SfE BES 2018 conference.

*Prof Lightman is pictured at the Goroka Festival, Papua New Guinea’s equivalent of Glastonbury! 

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

When I was appointed Professor of Medicine at the University of Bristol, very little endocrine research was going on there, which had the great advantage of providing me with a clean slate and the ability to develop my own research theme. Now I have a lab group that ranges from the very basic cell and molecular science through physiology, right up to clinical research. I really enjoy being able to translate up to humans and then back translate down again to animal models. Having a group of scientists and clinicians working together is a really exciting environment to work in.

Can you tell us a little about what inspired you into endocrinology?

I was always interested in human biology and my earliest research was in anthropology, which naturally led into human behaviour and to neuroscience. I initially wanted to be an academic clinical neurologist but at that time neurology research centred around the peripheral nervous system, and I was interested in the brain! The one way I could investigate brain function was through the window of hypothalamic-pituitary function, therefore I became a neuroendocrinologist. Since then I have been working at the interface of endocrinology and neuroscience, which I find fascinating.

What you are most proud of in your career so far?

I am most proud of the people that I have helped to train, who have gone on to do well afterwards. It is also really rewarding to have set up lots of collaborations with mathematicians, and fascinate them in the dynamics of hormones. They have of course also been very both for me and the subject, developing   the concept of hormone dynamics. With the exception of GnRH, endocrinology was often considered a homeostatic but relatively static science, where hormone levels are measured and found to be either too high or too low. This is clearly far from reality and trying to bring the idea of dynamic hormonal systems into the mainstream is something I have been very involved with.

Tell us what you enjoy about your role as President of the British Neuroscience Association (BNA)?

I love meeting lots of really interesting people. The brain is such an interesting area and I enjoy understanding how it interacts with all aspects of our lives. The BNA 2019 Festival of Neuroscience will be held in Dublin on 14-17 April 2019, and will be in collaboration with the British Society for Neuroendocrinology, and include a scientific symposium sponsored by the Society for Endocrinology. So, there will also be a strong element of endocrinology running throughout the meeting. However, it is a great event for bringing together lots of diverse areas of neuroscience.

What are you presenting in your Medal Lecture at SfE BES 2018?

I will be discussing how aspects of HPA physiology are governed by dynamics, from the stress response to the circadian rhythm. The underlying dynamics of this system are what allow us to be flexible and to maintain a homeostatic state. I will also be talking about improved ways of diagnosing endocrine disorders. If we can harness novel technologies to measure dynamic changes in hormone levels in patients at home, we can gather much better information for diagnosis and treatment.

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

From my own point of view the best part of the conference will be discussing posters with young, enthusiastic scientists right at the start of their careers. The posters are a really exciting area where people are putting out new ideas, in all areas of endocrinology. I like to be educated, so enjoy going to posters in areas where I don’t know much and hearing about what people are doing and why they find it exciting.

What do you think are the biggest challenges in endocrinology right now?

I think there are two main challenges, one of which I alluded to earlier.

  1. In terms of HPA the challenge lies around how we can measure dynamic changes in hormone levels in patients at home. I think the whole field of medicine is moving away from keeping people in hospital, to do lots of blood tests, sending them home, calling them back in to discuss results and finding you don’t have the right answer. Diagnosis can then be prolonged, inaccurate and very expensive, all of which is bad for patient care. The real challenge is finding better ways of doing this, and doing it in patients at home.
  2. Another challenge concerns the best way to give glucocorticoid replacement therapy. There is currently great debate on this in the field but it is important that we find the answer. Poorly managed glucocorticoid replacement is associated with considerable morbidity and mortality, so lots of attention is focused on finding a better way of doing it.

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

I think the ability to monitor patients’ hormone levels over a 24 hour period will be a major breakthrough, and will provide the basis for better understanding of normal physiology and better diagnostic methodologies.

We have been developing a wearable collecting device that can be worn by patients at home. Using this device, patients would need only a quick visit to have it fitted and another, 24 hours later to have it removed. This is sufficient to provide full tissue biochemistry over a 24 hour period. This would minimise the time in hospital and provide a personalised medicine approach with a wealth of data that gives an overall picture of the individual’s health. This type of approach could revolutionise diagnostics and really improve patient care.

Once we understand how to apply this technology we will have better more rational ways of targeting and timing treatments, to address the challenges mentioned in the previous question.

What do you enjoy most about your work?

I love the challenge of new ideas and using them to work out answers to important questions. It is also a pleasure and privilege to have the opportunity to work with great colleagues.

Who do you admire most in the world of endocrinology?

The first piece of endocrinology that ever excited me was Vincent Wigglesworth’s work on the hormone, ecdysone. He was a brilliant entomologist and his beautifully designed experiments on the extraordinary process of metamorphosis was a real eye opener. He was my first endocrine hero!

Any words of wisdom for aspiring endocrinologists out there?

Enjoy, enjoy, enjoy! You really need to enjoy your work, or you should be doing something else. I describe what I do as privileged play!

You can hear Professor Lightmans’s SfE Medal Lecture, “HPA activity: Don’t forget the dynamics” on Monday 19 November, in the Lomond Auditorium at 17:30. Find out more about the scientific programme for SfE BES 2018.

Meet the Endocrinologist: Leanne Hodson, expert on metabolic physiology

Meet Leanne Hodson, Professor of Metabolic Physiology at the University of Oxford. She specialises in changes in metabolism caused by nutrition including the metabolic consequences of obesity.  She has been awarded the SfE Starling Medal and will be delivering her Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, she tells us more about her career and what she is looking forward to at this year’s conference.

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

I am currently a British Heart Foundation Senior Research Fellow in Basic Science and Professor of Metabolic Physiology at the University of Oxford. The lab is focussed on research related to human health and metabolism; this includes the influence of specific nutrients and the consequences of obesity and obesity-related diseases, such as non-alcoholic fatty liver disease (NAFLD). Although our work has a focus on hepatic metabolic physiology, it covers a number of broader areas including: endocrinology, nutrition, hepatology, diabetes and liver transplantation.  We use a combination of human in vivo, ex vivo and in vitro models to undertake our studies.

Can you share some of your proudest career moments?

I am originally from New Zealand and had various career paths before eventually making it to University, where I obtained my PhD.  In 2004, I received the Girdlers Health Research Council (New Zealand) career development fellowship which provided the opportunity to work at the University of Oxford with Professors Keith Frayn and Fredrik Karpe. I was awarded a British Heart Foundation Intermediate Basic Science Research Fellowship in 2011, and became an Associate Professor of Diabetes and Metabolism in 2014. In 2015, I was awarded a British Heart Foundation Senior Basic Science Research Fellowship and in 2018 became Professor of Metabolic Physiology.

I am proud of many things including the reputation and the quality of work my lab, which leads to collaboration requests from well-respected and very talented scientists. Getting my fellowships, becoming a professor and getting the SfE Starling medal are definitely highlights. However, I am most proud of the environment I have been able to create for my research group, which is dynamic, productive and supportive – I am fortunate to work (and collaborate) with a wonderful group of individuals.

What are you presenting at your Medal Lecture at SfE BES 2018?

My group is interested in understanding why fat starts to accumulate in the liver and what the effects of insulin and specific nutrients or therapies are on this process, including the subsequent effect this then has on metabolism. In my Medal Lecture I will present what we have learnt over the last 14 years and how we have further developed and incorporated new models and state-of-art methodologies to study human liver fat metabolism.

Is there anything you are particularly looking forward to at this year’s conference?

I am very much looking forward to hearing the Early Career talks and going to the poster sessions, as it is a great chance to learn what work is coming out. Also I am going to the applied physiology workshops, as these are something I have not experienced before and I am sure I will learn a lot from them.

What do you think are the biggest challenges in your research area right now?

Developing models (particularly in vitro models) that better recapitulate the human disease that we are trying to study, as the historical ones, although interesting, are not reflective of human physiology.

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

Good question! I would like to think we will soon have more sensitive and specific biomarkers to detect the different stages of NAFLD. Improved biomarkers will allow us to study changes in hepatic metabolism at clearly defined stages during the progression of NAFLD, therefore increasing our likelihood of developing therapeutic agents to treat the disease.

What do you enjoy most about your work?

There are two things I most enjoy about my work:

  • the process of watching projects come to fruition and seeing the results come together is really exciting,
  • creating a supportive environment that challenges individuals to reach their full potential and grow in confidence.

Who do you most admire professionally?

Professionally, there have been many people (both senior and junior) past and present who I admire for a multitude of reasons; including their professionalism, patience, knowledge, determination, resilience and enthusiasm. They have passed on little gems of information – through their actions and words. These individuals know who they are and I cannot thank them enough for their support over the years.

I have been involved in the sport of rowing for over 30 years and, as a coxswain, I have been involved in boats that had world-class coaching and two coaches particularly stand out, despite their very different coaching manners. They both fostered a strong team commitment, had the ability to personalise their coaching to bring out an individual’s full potential (and beyond), and kept the focus on the process (rather than the outcome). For this I have huge admiration and have learnt to apply these techniques to my academic career.

Finally my grandfather, who passed away 4 years ago was a very important person in my life, along with a great work ethic (and zest for life) he was an incredibly well-respected rugby coach who had a unique ability to bring out the best in teams.

Any words of wisdom for aspiring endocrinologists out there?

Take the unexpected opportunities that present themselves (they could be the best decision you ever make) and if you are unsure find a mentor, who you trust and who is honest and constructive (listen to their advice, even if it is not what you want to hear). Remember that an academic career comes with disappointments. I don’t use the word failure as none of us fail, we just take different paths to successes, so it is important to persevere and build resilience but most importantly enjoy what you do!

 

You can hear Professor Hodson’s Starling Medal Lecture, “Hepatic fatty acid metabolism: the effect of metabolic and nutritional state” on Monday 19 November, in the Lomond Auditorium at 14:45-15:15. Find out more about the scientific programme for SfE BES 2018.

Meet the Endocrinologist: Maria-Christina Zennaro, expert in the genetic mechanisms of aldosterone-related disorders

Meet Maria-Christina Zennaro, a professor in the Paris Cardiovascular Research Center at the French National Institute of Health and Medical Research (Inserm).  She specialises in genetic mechanisms of aldosterone-related disorders. She has been awarded the SfE European Medal and will be delivering her Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, she tells us more about her work and what she 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 research professor heading the team exploring the genetic mechanisms of aldosterone-related disorders at the Paris Cardiovascular Research Centre at the French National Institute of Health and Medical Research (Inserm). My team is interested in unravelling the genetic and genomic mechanisms of aldosterone-related disorders, particularly primary aldosteronism, by combining clinical work with genome-wide strategies and mechanistic studies in cell and animal models. I am also an associated investigator at the Genetics Department of the European Hospital Georges Pompidou (HEGP) in Paris, where I coordinate the genetic diagnosis of pseudohypoaldosteronism type 1 and primary aldosteronism at the genetics laboratory, which is the French referral centre for the genetic diagnosis of these diseases.

What inspired you into endocrinology?

I received my MD and board certification in endocrinology at the University of Padova (Italy) and completed a PhD in molecular endocrinology at the University Pierre et Marie Curie in Paris. I had the chance to have great mentors, in particular Decio Armanini, who shared his passion for research with me, and John W Funder, who has supported my career ever since. In Paris, I had the chance to work with major players in the field of arterial hypertension and aldosterone, setting the basis for my future research.

What are you most proud of in your career so far?

After obtaining a tenured position as an Inserm researcher twenty years ago, I developed my own research group, which is now benefitting from the outstanding environment of the Paris Cardiovascular Research Centre and HEGP. I am particularly proud of having been able to create our research group, with the successive recruitment of two great researchers, with whom I have taken pleasure in sharing my working career with for many years.

What are you presenting in your Medal Lecture at SfE BES 2018?

I will present an update on the genetic and molecular mechanisms involved in the development of primary aldosteronism. In particular, I will summarise our current knowledge on the genetics of primary aldosteronism, notably our recent paper identifying a new gene in early onset primary aldosteronism, and discuss the pathogenic mechanisms leading to increased aldosterone production and cell proliferation. I will also discuss perspectives for clinical management of patients and open questions to be addressed by future research.

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

There are many great sessions on the adrenal gland, featuring world-leading experts in the field, which I highly recommend. There are exciting plenary lectures and I am looking forward to hearing about the influence of the microbiome in endocrine disease on Tuesday afternoon.

What do you think are the biggest challenges in endocrinology right now?

I think the challenges are threefold. First, the scientific challenge of improving our understanding of common and rare endocrinological disorders. Second, to be able to efficiently transfer this knowledge to patient care, in particular the knowledge generated from large-scale ‘omics’ studies. Improving diagnosis, management and implementation of precision medicine in clinical practice is really important, and should be affordable and available for everyone anywhere. Lastly, but not least, a major challenge is gathering funding for research in endocrinology.

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

I hope it will be the development of new diagnostic procedures for endocrine hypertension, which will have a major impact on treatment of those patients and prevention of cardiovascular and metabolic complications, improving their quality of life.

What do you enjoy most about your work?

Most certainly it is the scientific exchanges with my colleagues all over the world and mentoring young people to transmit my knowledge with passion to future generations.

Who do you most admire professionally?

I have had the chance to meet many extraordinary colleagues, many of whom I admire for different reasons. I particularly admire a few of my senior colleagues and mentors: I consider it a great opportunity to meet them every year at different meetings around the world, to have discussions with them and benefit from their profound scientific knowledge and incredible experience, especially when they talk about experiments they did 30 years ago!

Any words of wisdom for aspiring researchers out there?

Endocrinology requires a deep understanding of the complexity of endocrine feedbacks and interactions throughout the body. Research in the field of endocrinology is exciting, as it addresses the many questions we have on the mechanisms regulating endocrine physiology and hormone action. In this sense, it is also very diverse, ranging from genetics to cellular and molecular mechanisms, not only in hormone-producing organs but also in the multitude of target organs.

You can hear Professor Zennaro’s European Medal Lecture, “Molecular mechanisms in primary aldosteronism” on Wednesday 21 November, in the Lomond Auditorium at 15:30-16:00. Find out more about the scientific programme for SfE BES 2018.

Meet the Endocrinologist: Ursula Kaiser, expert in neuroendocrine regulation of puberty

Meet Ursula Kaiser, Professor at Harvard Medical School and Chief of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital. Her research is focused on neuroendocrine regulation of puberty, reproductive health and fertility. She has been awarded the SfE International Medal and will be delivering her Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, she tells us more about her work and what she is looking forward to at the SfE BES 2018 conference.

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

At Harvard Medical School and as Chief of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital, I lead and direct a group of over 60 clinical and research endocrinologists at a large academic medical center. My laboratory studies the genetic and molecular mechanisms underlying the neuroendocrine regulation of reproductive development and function, with an emphasis on the mechanisms regulating gonadotropin-releasing hormone (GnRH) and gonadotropin production. We use translational approaches including clinical and laboratory observations in humans, investigations in mouse models, and molecular and cellular studies to elucidate the molecular and biological underpinnings of reproductive disorders.

Can you tell us a little about what inspired you into endocrinology?

I grew up in Canada, where I received my undergraduate degree in biology at University of New Brunswick followed by my medical degree at University of Toronto. Early in medical school, I became fascinated by the feedback loops of endocrinology and by the many systems affected by hormones, and was quickly convinced that endocrinology was my calling. I completed my clinical training and licensure in internal medicine and in endocrinology in Toronto, but became intrigued by the molecular underpinnings of endocrine disorders. I moved to Harvard Medical School and Brigham and Women’s Hospital to pursue basic science research training in the regulation of gonadotropin gene expression under the mentorship of Dr. William Chin in the Genetics Division. My initial research focused on the mechanisms of differential regulation of luteinising hormone and follicle stimulating hormone; more recently, I have moved “further up” the hypothalamic-pituitary-gonadal axis to study the neuroendocrine regulation of GnRH secretion.

What you are most proud of in your career so far?

Scientifically, I’m most proud of our discovery that mutations in a gene known as MKRN3, or Makorin Ring Finger Protein 3, cause central precocious puberty. This was the first major genetic cause of precocious puberty to be identified and is now recognized to explain close to half of all cases of familial central precocious puberty. This discovery has identified the first known inhibitor of human GnRH secretion and has opened up an entirely new field of investigation. It is also important translationally and has highlighted the role of genetic imprinting in the control of human pubertal timing. I’m particularly proud of this accomplishment because of its collaborative and multidisciplinary nature – it has involved an international network of collaborators and has helped to launch the careers of several of our trainees.

What are you presenting in your Medal Lecture at SfE BES 2018?

I will be talking about our discovery of the role of MKRN3 in the timing of puberty and the link of loss of function mutations in MKRN3 with central precocious puberty.  In particular, I will expand on the studies we have performed since discovering this link in order to better understand the role and mechanisms of action of MKRN3 in puberty onset.

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

I’m particularly looking forward to seeing my British and other international friends and colleagues, to catch up and hear about their new work, and to discuss ongoing and potential future collaborations. One thing that I would recommend to others is to take maximum advantage of the opportunity to catch up with new advances in their fields and to network with colleagues. It’s a great opportunity to meet new colleagues and make new connections!

What do you think are the biggest challenges in endocrinology right now?

Two of the biggest challenges in endocrinology are addressing the rising rates of obesity and diabetes mellitus. The prevalence of these metabolic disorders is rapidly increasing, not only in developed countries, but also in the developing world. We need more research to better understand the pathogenesis of these metabolic disorders. Interestingly, neuroendocrinology is increasingly recognized to play a key role in metabolic disorders, with neuropeptides and neural circuits playing key roles both in appetite and energy homeostasis, as well as linking metabolism to other areas of physiology such as reproduction and growth.

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

I believe that neuroscience is an incredibly exciting area that is poised for major breakthroughs. The combination of advances in human genetics together with advances in our abilities to study the brain are allowing neural circuits to be mapped in detail and are leading to new discoveries in mechanisms underlying neurological and neuroendocrine diseases. I am hopeful that these advances will in turn lead to new treatments for these disorders. Endocrinology is particularly important for our understanding of sex differences in predisposition to and responses to treatments for neurological disorders, such as Alzheimer’s and Parkinson’s disease.

In addition, advances in our understanding of neuroendocrine circuits will lead to new therapies targeting neuroendocrine pathways controlling metabolism and reproduction. The recent discovery that menopausal vasomotor symptoms (i.e., hot flashes) are mediated by the neuropeptide, neurokinin B, and that neurokinin B antagonists can effectively target and reduce the frequency of these vasomotor symptoms, is a great example of such a breakthrough.

What do you enjoy most about your work?

I’m so fortunate to have one of the best jobs in the world! My work is intellectually and socially stimulating. No two days are alike – between teaching students, doing research, and seeing patients, I’m learning new things every day. I have wonderful opportunities to meet and interact with a broad variety of interesting and kind people.

Any words of wisdom for aspiring endocrinologists out there?

Endocrinology is a fantastic field! The diversity of endocrine disorders and the multi-system effects of hormones leads to a very integrative field that is intellectually stimulating and satisfying. There is still so much to be learned and so many research questions to be answered. Furthermore, the endocrine specialty provides the opportunity to have sustained, long-term relationships with patients and to observe the impact of treatment on their health and quality of life.

You can hear Professor Kaiser’s International Medal Lecture, “Puberty: what are the neuroendocrine triggers for the biological end of childhood?” on Monday 19 November, in the Lomond Auditorium at 14:15-14:45. Find out more about the scientific programme for SfE BES 2018.

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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.