September 2018 – The Endocrine Post

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

Published on 24/09/201804/10/2018 by Society for Endocrinology1 Comment

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

Published on 18/09/201818/09/2018 by Society for Endocrinology2 Comments

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: Caroline Gorvin, expert in hormone receptor cellular physiology

Published on 04/09/2018 by Society for Endocrinology1 Comment

Meet the Endocrinologist: Caroline Gorvin, expert in hormone receptor cellular physiology

Dr Caroline Gorvin is an Institute of Metabolism and Systems Research Career Development Fellow at the University of Birmingham. Her research focusses on the trafficking and signalling of membrane proteins, particularly GPCRs and how impairments in these proteins and their signalling pathways contribute to endocrine disease. In this interview, Caroline tells us more about her research, involvement with the Society and her roles as convenor of the Society’s Bone and Calcium Endocrine Network.

Can you tell us what inspired you into research?

My year in industry, which I spent at AstraZeneca during my undergraduate degree, really changed my perspective on research. Prior to this, I wasn’t even sure I wanted to do a PhD, but the experience of scientific research really ignited my interest in membrane proteins, which I have, in some way, continued to work. I accidentally became an endocrine researcher because of this initial interest in membrane proteins and receptors. I realised that genetic abnormalities in these proteins often manifest in endocrine disease, and that by studying these mutations we can learn fundamental concepts about cell behaviour that may help in the treatment of patients with endocrine disorders.

Can you tell us a little more about your current research?

In the last five years, my research has focussed on the calcium-sensing receptor (CaSR), which is a G-protein coupled receptor that has an important role in calcium homeostasis. The CaSR is a great receptor to work on because both loss-of-function and gain-of-function mutations cause disorders of calcium homeostasis, with opposite phenotypes. By studying these mutations in vitro we have been able to understand how individual residues play a role in receptor activation and mediate coupling to specific signalling pathways.

I have found my most recent research, focussed on how mutations in a subunit of the adaptor protein-2 cause hypercalcaemia really fascinating. We could never have predicted that a protein, which is known to play a fundamental role in clathrin-mediated endocytosis, would be the cause of hypercalcaemia. By studying these mutations I was able to uncover novel signalling and trafficking mechanisms of the calcium-sensing receptor, which could represent new therapeutic targets. This project also gave me the opportunity to collaborate with lots of people, and learn new techniques, which to me are the most exciting parts of being in scientific research.

Over the last decade or so, what do you think have been the most impactful advances in this research area?

I think the technological advances in the last decade have really had the most impact on all scientific research. We can now rapidly introduce specific mutations into genes, sequence the whole genome in individual patients and visualise single molecules in cells. These advances have the potential to reveal minute details about cellular and whole organism physiology, expand our knowledge of disease mechanisms and fundamentally improve patient treatment options.

What do you think will be the next big or important breakthrough in bone and calcium research?

I think long-term regenerative medicine is probably the biggest goal in bone and calcium research. With an ageing population, skeletal disorders such as osteoporosis are increasing in prevalence. While we have good therapies to manage symptoms, new technologies offer the possibility of treatments with fewer side effects. Many advances have been made in this field in recent years, and with improvements in bioengineering and iPS cell technology, long-term bone regeneration is becoming a feasible possibility.

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

I think the biggest challenge all researchers face is funding. In endocrinology, where much of the research is into rare disorders, and therefore necessarily niche, it can be difficult to persuade big funding bodies of its importance. There seems to be a wider field of competition, for an ever-decreasing pot of money. Combined with the sometimes poor career advancement opportunities, particularly for basic science researchers, I think these difficulties pose the biggest challenges rather than research specific difficulties.

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

There are always controversies in any research area. Instead of creating hostility, these controversies should be used as an opportunity to debate and explore new ideas. One of the fantastic things about science is that we don’t know the answers. We should enjoy exploring differing opinions through debate and further research.

You were awarded a Society Public Engagement grant in 2017, why do you think it is important for scientists to get involved?

While many people realise that scientific research takes place, what this actually entails is largely unknown. By introducing people to our work in a fun and informative way, I think we can help make this clearer and gain more support for what we do. Public engagement is really important for science and is mutually beneficial. By encouraging participation we can attract the next generation of scientists, and by sharing our ideas with the public, we may gain new perspectives to enhance our future research.

What attracted you to becoming an Endocrine Network convenor, and how do you think the Networks may benefit others?

To be honest, I was nominated for the position, and hadn’t previously considered that such a position was open to someone relatively early in their career like myself. Initially, when I first started attending the SfE BES conference as a PhD student, it really felt like bone and calcium science was a neglected part of the meeting. This has been changing in the last five years or so, with more bone and calcium research on the oral programme – but I still think research, and collaborations within the field, could be promoted more and the network is good platform for this. One way in which myself and Jeremy Turner, my co-convenor for the network, have been trying to do this is by increasing communication within the network, and giving members the opportunity to say what they want from the network. The network has great potential to generate discussion and new collaborations between basic and clinical scientists – I guess we’ll see how successful this has been at this year’s SfE BES conference!

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

I think the best advice for anyone in research is not to be too disheartened by failure. Just remember everyone in research will have had days where experiments failed, or had papers and grants rejected. We often don’t realise this as PhD students, but it is a valuable lesson that everyone should learn in their scientific career.

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