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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.

 

 

Featured

Meet the Endocrinologist: Interview with Prof Antonio Vidal-Puig

Group Photo - June 2017

Meet Professor Antonio Vidal-Puig, endocrinologist and Society for Endocrinology Medal winner for 2017. Prof Vidal-Puig is based at the Institute of Metabolic Sciences, Cambridge University and at Addenbrooke’s Hospital, where his outstanding research, focusing on the link between obesity and associated metabolic complications, has earned him this award, to be presented the annual conference, SfE BES 2017, in Harrogate, 6-8 November 2017. Learn more about his endocrine journey in this exclusive interview.

Q: Tell us a little about your career so far and how you ended up in Cambridge.

Originally from Spain, I studied medicine and trained in endocrinology at Valencia Medical School and Granada Medical School. I held post-doctoral positions in Boston at the Massachussetts General Hospital and Beth Israel Hospital/Harvard Medical School from 1992-1999. There I had excellent mentors including Jeff Flier, Brad Lowell, David Moller and Leo Krall. This was a very intense, exciting and uncertain period, at the epicentre of major discoveries in the field of obesity. This was a period that defined my career, scientific focus, approach to science and reinforced my values. I have been developing my career in the UK, since arriving at Cambridge University in 2000, and now have an established laboratory and have become a Professor of Molecular Nutrition and Metabolism.

Q: Tell us more about your research that led to you being awarded the Society Medal

The lab is interested in why obesity results in diabetes, insulin resistance, fatty liver and ischaemic heart disease, in order to find ways of preventing these complications.

The key concept of our programme is lipotoxicity, which links obesity-related metabolic complications with the excessive accumulation of lipids outside adipose tissue, in organs including muscle, liver and heart. From the concept of lipotoxicity we have developed three main research directions:

  • understanding how the adipose tissue works, with the aim of improving its function and ensuring that lipids remain in adipose. This led to the development of our “adipose tissue expandability hypothesis”, which is now widely accepted by the scientific community
  • developing strategies to burn the excess lipids and prevent lipotoxicity through activation of brown fat
  • promoting that the quality of dietary lipids should be as healthy as possible, to prevent toxic effects.

My Medal Lecture at SfE BES 2017 will summarise our contribution to these three directions.

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

I will use this conference for updating clinical aspects of my work. The presentation quality is always good and helpful. One session I am really curious about is Workshop 1: Tissue Engineering for Regenerative Medicine in Endocrinology. I think technology is essential to retain a competitive position in research and the topics presented are highly transferable and of interest. I think tissue engineering approaches to increase brown fat mass could be really helpful in preventing obesity and diabetes, I am curious about the concept and possibilities of using 3D bioprinting.

Q: What have been your career highlights so far?

I feel content about my career progression. I consider highlights to be our best pieces of research; our papers tend to be quite comprehensive and we believe they make important contributions. I think for this reason these contributions are well respected by our colleagues. Our reputation as a lab is important for us. Also as a proud introvert, I have not touted our highlights and have not needed to for our professional highlights to be widely acclaimed, however I do understand that it is important to make the public aware of their implications. Also, as a laboratory leader I know that to disseminate these highlights is important for the careers my lab members. In this respect, winning the Society for Endocrinology Medal is a highlight that reflects the quality and commitment of the present and past members of the laboratory.

At a more personal level, I admit I have an aesthetic approach to science. I enjoy understanding and identifying sophisticated mechanisms, developing models that explain reality and learning how biological systems self-regulate. I don’t think this is unusual amongst endocrinologists. Also, becoming a Professor at Cambridge University was a moment of satisfaction I shared with my colleagues and family. In some ways my career has provided me with professional freedom, which is a key value for me, beyond other motivations, such as power or fame, that I have always found energy draining and restrictive of my autonomy.

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

I think a big challenge in my research area, and others, is how to extract value from the excessive information generated by recent technological advances. Our challenge is how to analyse this information to prioritise the types of mechanistic validation that are necessary for estimating its relevance. Also, it is not only the amount of data, but the amount of unnecessary noise coming from poor quality research that makes this task more difficult.

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

As you become more senior in science, you often suffer the disadvantage that your professional horizon is shorter. However, this position also has the advantage that you can be more selective in your choice of projects, with more freedom to take risks. I think my laboratory in this respect is quite entrepreneurial, we are innovating by entering new fields/technologies, which I think is important for remaining competitive.  For example, we have opened a new lab at Sanger, funded by the European Research Council to work on stem cells and adipose tissue. We are also developing two new programmes of research; one in Nanjing focused on murine models of fatty liver, and another in Bangalore focused on adipose tissue stem cell biology to model obesity and diabetes in India. These are exciting challenges that will provide opportunities for my younger associates in their future careers.

Q: Who do you most admire professionally?

I have learned a lot from many of my mentors, colleagues and trainees. In some way these experiences have shaped my values and my strong views about science and leadership. For example, I have always admired the intellectual rigour and scientific honesty of Brad Lowell. I admired the consistency and confident leadership of Jeff Flier and the legacy of Daniel Lane, who developed many academic scientists in his lab to share his cultural values and collegiality, which they now disseminate to the next generations. I find this very impressive.

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

Endocrinology is not a specialty that will make you rich, but it is a specialty where you can fulfill your intellectual scientific needs and enjoy the human aspect of practicing medicine. It is very satisfying because your patients get better and, given that treatments are required long term, an important factor in the success depends on establishing an empathetic relationship with them. You will get to know many of your patients well, from whom you will receive gratitude and a sense of meaning and fulfillment. In this respect it is a very rewarding profession.

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

I think real breakthrough with long term impact requires deep knowledge and new technologies, I have become quite sceptical about quick or easy breakthroughs that address complex problems. It is important to understand how regulatory systems operate, to learn what the adaptive changes of the organism or cell to maintain normality are, and to determine the intrinsic capacity of these systems to recover normality if the early factors of the disease are removed. For this reason, we focus on early disease events, aiming to prevent or reverse excessive damage to the homeostatic system and regain metabolic control. In this sense, we think it is as important to learn how the problem occurs as it is to learn the trigger and why it occurs. In our field I think understanding how lipids mediate disease could be used for prevention, early diagnostic and therapeutic purposes.

You can hear Prof Vidal-Puig’s Society for Endocrinology lecture on Wednesday 8 November, 15:45-16:45, and see the full scientific programme for SfE BES 2017.

How can we inspire our future leaders in endocrinology and the Society?

Graham Williams with Award winners SfE BES 2017
Prof Graham Williams (centre) with Award winners SfE BES 2017

The Society has launched a new Leadership & Development Awards Programme, to recognise and nurture emerging talent in endocrinology and help Awardees become the future leaders of our discipline. In our interview, Prof Graham Williams, President of the Society for Endocrinology, introduces the Awards Programme and explains how it will be used to inspire and support our leaders of tomorrow, and why early career endocrinologists should apply.

What are the aims of the new Awards programme?

My main priorities as President of the Society have been to ensure that we cater for every member and that we are prepared for the future by being able to develop and respond to change. An important part of that is to support people who are enthusiastic and dedicated to endocrinology so they are equipped to be our future leaders. The Society Officers and Council have introduced the Leadership & Development Awards Programme to help identify these individuals and prepare them; by providing opportunities to learn more about how the Society works, how it is governed, how the committees work and what its strategic aims are. The main purpose is to give everybody an equal opportunity to become more involved, and to ensure that all categories of our membership are well represented in the future.

Towards this goal, the Awards Programme is open to clinicians, clinicians-in-training and research scientists. We are also considering, with the Nurse Committee, how to bring forward a similar initiative that will suit our nurse members, who have different career pathways and needs, and will require an alternative selection process.

The overall aim is to ensure the Society is in a strong position for the future, by securing the engagement of our most dedicated members to help grow and develop our community.

Why do we need an Awards Programme to identify our future leaders?

Our members have always been engaged with endocrinology but the discipline is rapidly changing. It is no longer so easy for people to identify themselves as endocrinologists. There has been a move away from a traditional organ and disease based focus, with increasing emphasis towards interdisciplinary science, whole organism physiology and cellular and molecular signalling. This means many more people are dipping in and out of endocrinology as a discipline, which in turn impacts on the Society. We need to move with the times and ensure we include cross-cutting disciplines that are integrated fully within the Society and endocrine community.

What are your hopes for the Awards Programme in the longer term?

I don’t want to predict the future but I think the Society needs to be agile and responsive as the discipline changes. So we aim to equip Awardees with the skills they need to influence Society strategy and develop our plans as the field advances. Endocrinology is also global discipline and I think that building collaborations with other medical disciplines will be essential both in the UK and also with colleagues all over the world.

What advice would you give to applicants for the Award?

Answer all the questions as completely as possible but most importantly be yourself. When people answer honestly, it allows them to express their true sense of excitement and enthusiasm – and that is what we are looking for – people who are the ‘enthusiastic doers’.  Of course we are looking for those who can demonstrate clinical and scientific excellence in endocrinology, but they need to be excellent communicators and ambassadors as well.

What qualities do you think are important in our future leaders?

I think openness, honesty and the ability to listen to, and to take advice from, others are some of the most important leadership qualities. By sitting on lots of committees you can learn a lot from the chairs. The best ones are great listeners, adept at summing up and have the ability to direct people towards a sensible consensus. Excellent communication skills and wanting to help others are essential qualities for all leaders.

Apart from a dedication to endocrinology, it is important that Awardees are rounded individuals with other outside interests . Working hard is important but it is important to switch off at times and enjoy other interests.  For me this has come from sport and the great outdoors, but whatever it is “work hard and play hard” and you won’t go far wrong!  Having diverse interests also helps with networking, getting to know colleagues and in developing long-lasting friendships that cement the endocrine family together.   

What have you enjoyed most while serving on Committees and as President?

It has to be the people. I feel in a really privileged position to be able to work in the field I love, but serving the Society has extended that experience into being part of a community. Being able to meet and work with like-minded and fantastic people, from different disciplines, from all over the world, and who all want to achieve similar things has been very inspiring.

Who were your early mentors?

I have been fortunate to have had many outstanding mentors over the years but here are the early ones that inspired me into endocrinology and then research. As a medical student, I loved anatomy and was all set to be a surgeon.  However, my first house job was with Professor David London at the Queen Elizabeth Hospital in Birmingham.  He is an eminent clinical endocrinologist and long-standing Society member.  During my time as his houseman, we had lots of interesting endocrine challenges and his infectious enthusiasm got me hooked, so I decided to change and take up a career in endocrinology.

After completing general medical training, I was encouraged to move into the laboratory to work on thyroid hormone action with Michael Sheppard and Jayne Franklyn.  They subsequently encouraged me to branch out and go to Boston to continue my research training at Harvard Medical School, and this move inspired me to pursue an academic career in basic clinical science.  Throughout my career many people have been inspirational and provided support and this never stops; you develop an expanding network that brings new ideas, collaborations and opportunities.  It is here that the Society makes such a difference and will continue to do so as the next generation takes the reins and leads us into the future.

I feel strongly that the new Leadership & Development Awards Programme will serve the future of the Society and the future of endocrinology well.  It will provide unique opportunities for those who apply and I hope it will help to support the careers of our talented trainees.  The applications are open to all so please don’t feel inhibited – just go for it!

Are you an early career endocrinologist interested in developing your leadership skills and becoming more involved with the Society? Applications for the Leadership & Development Awards Programme are open 1 April – 14 May 2019.

Full details of the selection process, benefits and how to apply are on our website.

Tackling inaccurate and misleading reporting on science in the media

A story published on Saturday in The Times has provoked outrage amongst some Society members.

Dr Richard Quinton and Dr Channa Jayasena, two of our expert Media Ambassadors, contacted the Society Press Office to express their grave concerns over the article: The £195 hormone cream that’s changed my life by Olivia Falcon.

Both Dr Quinton and Dr Jayasena feel that this article is written and presented in an irresponsible way that is misleading to the reader, on a potentially unsafe and improperly tested product. The Society is committed to helping promote accurate and responsible reporting of endocrinology-related topics in the media, so we passed their concerns, in the form of the open letter below, to The Times.

Dear Editor

In 1916, a $20 fine was levied in Rhode Island, USA for the misbranding of Clark Stanley’s Snake Oil Liniment to treat rheumatism and bunions and animal bites. The term ‘snake oil salesman’ is still used today to describe someone who knowingly sells fraudulent goods. Anti-ageing products are in ever-increasing demand. Whereas, cosmetic (i.e. non-medicinal) products are established in the market, there is growing speculation that hormone (endocrine) supplementation could provide additional benefit for older men and women. However, it is critical to understand that products claiming to alter the endocrine (hormone) system should be termed drugs, and are quite rightly subject to rigorous safety regulation. Crucially, the websites from which Endo-Test cream can be purchased explicitly state that “it is for scientific or laboratory use only and not for human consumption”.

Endo-Test cream described in last Saturday’s edition claims to ‘increase testosterone levels dramatically’ and nearly double sperm count and The Times’ journalist reported that these claims were based on an independent study by the manufacturer. However, we were unable to find any evidence of scientific peer review or publication of these findings. Furthermore, there is currently no medication in existence known to increase a man’s sperm count, so the findings appear improbable.

Interestingly, whereas The Times’ journalist correctly described Endo-Test cream as a “hormone cream”, the AQ company website claims prominently that Endo-Test is “hormone-Free”. For the record, the cited ingredients include a human androgen (testosterone-precursor) hormone (DHEA), a major insect moulting hormone (20-hydroxyecdysone) and a synthetic hormone (Gonadorelin) whose clinical application in humans is to shut down reproductive hormones entirely for men with prostate cancer and women with endometriosis, or as part of hormone treatment of trans-gender individuals. The extent to which these are absorbed through the skin, as opposed to through their conventional routes of administration, has likewise not been substantiated. 

To protect the interests of the public, it is important that manufacturers make substantiated claims and that journalists scrutinise evidence of these claims prior to publication. Without this, how would people know whether or not ‘snake oil’ was indeed the fountain of youth?

Dr Richard Quinton MA MD FRCP, Consultant Endocrinologist, Newcastle-upon-Tyne Hospitals

Dr Channa N. Jayasena PhD FRCP FRCPath, Clinical Senior Lecturer in Endocrinology, Imperial College London

Declaration: Both are Investigators on the National Institute of Healthcare Research (NIHR) funded Testosterone Efficacy and Safety (TestES) Consortium, and Media Ambassadors for the Society for Endocrinology*

*Please note these views are of expert members Channa Jayasena and Richard Quinton, and do not necessarily reflect the official position of the Society for Endocrinology.

The Times is now looking into the matter and will report back to us on how this will be addressed shortly. Our Media Ambassadors have successfully worked with Health and Science correspondents at The Times in the past to ensure accurate and responsible reporting, and we look forward to continuing to work with them on endocrine-related stories in the future.

UPDATE 8 March 2019 – The Times have now taken this article down, we thank them for their assistance with this matter and taking this positive action.

The Society is committed to engaging journalists, patients and the public with hormone science to encourage informed health decisions, and to demonstrate the value of endocrinology to the wider world. Our Media Ambassadors are experts that work alongside the press office to help provide expertise, context and analysis to promote accurate and responsible reporting.

If you are interested in helping to improve the quality of science and health reporting, read our Media Ambassador guide or email media@endocrinology.org to find out how you can get involved.

 

 

 

 

 

 

How an endocrine disease may have shaped British history

At SfE BES, Ashley Grossman, Professor of Endocrinology at the Oxford Centre for Diabetes, Endocrinology and Metabolism, gave a presentation entitled, ‘What killed Queen Mary’. In our latest interview, he tells us about his investigation into the unclassified illness that plagued Queen Mary and ultimately led to her premature death, and what we can learn from her tragic story.

Can you tell us why you think Queen Mary’s death was endocrine related?

Reading through Mary’s life history, which is quite a sad story, it seemed to me that something endocrine-related may have been going on and I came up with some interesting conclusions about her death. Mary was unfortunately plagued with illness throughout her life and her documented symptoms included her periods stopping, she starting to lactate, suffered from increasingly bad headaches and, just before Mary died, she began to go blind. All of these symptoms suggest she was suffering from an expanding prolactin-secreting pituitary tumour. Increased prolactin levels would explain her lactation and amenorrhoea. As the tumour expanded it would have compressed the brain, including the optic nerve leading to blindness. It may also have made her infertile explaining her failure to produce an heir. Ultimately, as the tumour expanded it likely placed pressure on vital areas within her brain  that may have been the cause of her early death in 1558 at age 42.

What sparked your interest in Queen Mary?

 I confess, initially I did not know much about history or Queen Mary. However, when my third daughter pursued history as an undergraduate and then as a Master’s degree student, it sparked my interest. I delved in and began reading books on the Tudors and Mary seemed quite fascinating. The fact that she died so young and childless was pivotal, as it completely altered the course of British History. If she had produced a child, then Britain would have remained catholic and Phillip II would have become King, dramatically changing history, with no future Elizabeth I on the throne.

Is there any way we could prove your theory?

Of course, the conclusion that Mary died from a pituitary tumour remains speculation. However, renowned Austrian physician – Victor Cornelius Medvei, whose passion for endocrinology led him to write the definitive textbook – A History of Endocrinology – also investigated the death of Queen Mary in some detail. To my delight his conclusions, discussed with Prof. Howard Jacobs, matched my own and reading his research really firmed up what I thought.

Mary’s buried in Westminster Abbey, so we could do a computerised tomography scan of her coffin to see whether or not her pituitary was indeed enlarged. However, I don’t think the monarchy would be very happy for anyone dig up her coffin and do that! To make a diagnosis on someone who lived hundreds of years ago is not hard science, but it is amazing to think that a pituitary tumour changed the course of British history.

What can we learn from your research?

Although historical, I think there certainly are things people can learn from Mary’s tragic story. I believe it’s important that people recognise how much life has been transformed by modern medicine, and how lucky we are to have treatments to disorders that just a few hundred years ago were highly debilitating or even lethal. For example, what destroyed the catholic British monarchy can now be treated simply with a few tablets and the disease might virtually disappear.

Ashley Grossman presented ‘What killed Queen Mary’ at the annual SfE BES conference in Glasgow on 20 December 2018. Discover more about the work of endocrinologists in our Meet the Endocrinologist series of blog interviews.

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.