Month: October 2022

Professor Peter Croucher is the interim Executive Director of the Garvan Institute in Sydney. His main research focus is tumours that grow in the bone, such as multiple myeloma, or those that metastasise to bone, including breast and prostate cancer. In this interview he discusses his career path which led him to bone biology, the exciting developments happening in his field and gives top tips for aspiring endocrinologists.

Tell us about your career so far

I did my initial training in zoology at Cardiff University, followed by a PhD in cell biology at the medical school in Cardiff. I then spent time in Cambridge before moving to the University of Sheffield to specialise in skeletal disease. After a stint at the University of Oxford I returned to Sheffield as a Professor of bone biology and ran the department of human metabolism. Here we set up an institute called the Mellanby Centre for Bone Research. Then 10 years ago, I was approached by the Garvan Institute of Medical Research in Sydney to lead their bone programme and I’ve been there since. Over the last few years, I’ve been head of various parts of the Garvan Institute, most recently the deputy director and then in the last three months, the Interim Executive Director. It’s pretty varied and has been an adventure, which has been fun.

What drew you to specialise in bone biology?


After doing zoology, I was offered the opportunity of doing a PhD in the medical school, and I worked with Juliet Compston, who is an expert on osteoporosis.. Since then I’ve always worked in skeletal biology, or cancer of the growing bone.

. “Probably my biggest highlight has been the ability to work with some wonderful colleagues”

Tell us about your current research

One of the major projects I’m working on is trying to understand why cancers grow in the skeleton. There are a number of cancers that grow in the skeleton with –  multiple myeloma is one example, and breast and prostate cancers can also spread from primary tumours to the skeleton. We do know that once they’ve spread to the skeleton, they’re difficult to treat and often regarded as incurable, causing devastating effects to the skeleton and bone disease. We are trying to understand why tumours grow in the in the skeleton, what controls an individual tumour cell when it first arrives in the skeleton and why these cells can live in a long-term, dormant state before they get woken up to form active disease. If we can understand what holds them in a dormant state and then what causes them to wake up this will help us identify new therapeutic targets in order to eradicate these cells and stop the cancers growing in the skeleton.

What are your career highlights so far?

My highlights are typically associated with the people I have had the pleasure of working with or with scientific discoveries associated with these collaborations. A good example was the first time we saw a dormant cancer cell in a living animal, and then being able to isolate those cells to work out all the genes that control the behaviour of those cells. This was a important as it opened up the prospect of being able to tackle an important clinical challenge for the first time. However, probably my biggest highlight has been the ability to work with some wonderful colleagues; both withi the Garvan Institute but also in laboratories across the globe. It is enormously satisfying to be able to work with great colleagues to be able to tackle important scientific and clinical questions.

What are the biggest challenges your field faces?

Some of the most exciting area are new imaging approaches, for example intravital imaging, which in our case is allowing us to find very rare cancer cells and study them for the very first time in living organisms. The advent of approaches to sequence an individual’s genome, or to work out all the genes that are switched on in a particular cell are exciting new developments. Being able to analyse this data at a scale that was not previously possible is truly exciting .

“Do things that are difficult and are going to have impact”

What are the most exciting developments happening in your field?

Some of the most exciting things are imaging approaches, which allow us to find very rare cancer cells and study them for the very first time. Also data science and the advent of approaches to sequence an individual’s genome, or to work out all the genes that are switched on in a particular cell and be able to analyse that at scale that we’ve never really had until the last couple of years. I think the developments and opportunities that come with these discoveries are really important.

What’s coming up at your SfE BES lecture?

I’ll be talking about how we’ve been successful in finding very rare, dormant cancer cells in the skeleton. We’ve been using single-cell sequencing approaches to identify the genes that control dormant cancer cells and the various specialised environments where they live. I’ll also explain how this provides important insights into what controls dormancy and how we might be able to use this information to target and eradicate these cells in the future.

What advice would you give someone starting out in the field?

I would say to identify an area that you feel passionate about, then to try and address an important question that’s going to have a big impact in that area. Do things that are difficult and are going to have impact.

You can attend Professor Peter Croucher’s 2022 International Medal Lecture “Insights into the Cell and Molecular Control Pathways that Regulate Cancers in the Skeleton“ on Tuesday 15 November from 9:00 – 9:30am.

Take a look at the full scientific programme for SfE BES 2022.

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Professor Mark McCarthy is Executive Director of Human Genetics, and a Principal Fellow at Genentech, where he leads research in human genetics to advance molecular understanding of health and disease. In this interview he tells us about his career, the people who have shaped his experience in endocrinology and what we can expect from his SfE BES lecture.
 
Tell us a little about your career so far

I trained in medicine at the University of Cambridge, then St Thomas’, working through medical SHO and Registrar rotations at Barts and the London School of Medicine and Dentistry (the London). One of which was endocrinology, and that became my chosen specialty. I fell into the research program that Graham Hitman was leading at the London on the genetics of type 2 diabetes. The first couple of years of research were difficult, but by the third year, I felt I was making progress. To test my research confidence a bit further, I secured an MRC Fellowship in Boston with Eric Lander, which was pivotal. I came back to a position in the UK after that which was half clinical and half research, but as the years went by, I found myself doing more research and less clinical work. I moved to Oxford in 2002 as the Robert Turner Professor of Diabetic Medicine, where I led a global research group that focused on the genetics of type 2 diabetes, obesity and related conditions. In 2019, I moved to Genentech, to lead up their efforts in human genetics (across multiple disease areas), putting what I had learned in Oxford to support target and biomarker discovery.

What attracted you to endocrinology?

It was pretty clear from my time as a student that I was going to be a physician, not a surgeon. So I rotated through a series of medical SHO positions before ending up in endocrinology. Two things about that rotation convinced me that this was the direction I wanted to go in. First, I was fortunate enough to work for John Monson, the endocrinologist at the London, who was just the most fantastic mentor and paragon of medical excellence – I owe him a huge debt of gratitude. Second was the practice of endocrinology itself – endlessly fascinating, (mostly) logical, and, for many patients, transformative.

“The practice of endocrinology itself [is] endlessly fascinating, (mostly) logical, and, for many patients, transformative.”

What is your career highlight so far?

I had the opportunity to be part of the team leading the Wellcome Trust Case Control Consortium, which in the mid-2000s performed the first large-scale, genome-wide association studies. It was thrilling to be part of such a seminal study. We didn’t know if it was going to work out, and there were huge technical and computational hurdles that the team had to overcome, but the study really transformed the field of common disease genetics and set in motion the explosion in our understanding of these conditions over the past 15 years. During the project I was particularly involved in type 2 diabetes, which revealed the first common variant influencing the risk of obesity.

Who have been your mentors?

There were three people who had a significant impact on my career. John Monson, who instilled in me a passion for endocrinology and a commitment to the ethical aspects to practising medicine and science. Graham Hitman, who guided me through my first few traumatic years in the lab, and pushed me towards more computational and analytical research (which was a good thing since I was much safer with a keyboard than a pipette). And Eric Lander who welcomed me into his lab in Boston, and gave me the belief that I could thrive in research.

What do you think are the most exciting breakthroughs in your field?

We are going through a revolution in research that brings together three complementary advances. Increasingly we are able to gather genetic and genomic data with both massive scale and high resolution. This started with human genetics and the ability to do genome wide association scans (rather than having to look one gene at a time), but we see the same now in genomics, for example through the power of single-cell and spatial genomics. We are also now able to gather data in humans, rather than animal models, which to state the obvious is the species we are most interested in. That’s in part down to genetics, but also through developments in the research of cellular and organoid models from human sources. Finally, we have these awesome advances in computational methods (most obviously in machine learning and AI) which allows us to make sense of vast, complex and diverse data sets.

“We have these awesome advances in computational methods (most obviously in machine learning and AI) which allows us to make sense of vast, complex and diverse data sets.”

What are the biggest challenges your field faces?

Too much of the data we have comes from European populations, so there’s much more that needs to be done to ensure that we embrace diversity in research and translation. Also we still have some way to go to ensure that we make use of these rich and diverse data sets to guide us to safe and effective ways of improving patient care.

Tell us what’s coming up in your SfE BES 2022 Medal Lecture

One of the most exciting developments in human genetic research relates to the use of polygenic risk scores. These aggregate data across multiple small genetic effects, and are becoming increasingly powerful at identifying those at extreme (whether high or low) risk of disease; and in some cases, in dissecting some of the clinical heterogeneity that we see in many of these conditions (with regard to progression, complications, and therapeutic response). I am going to describe three examples from my own research that I hope will give some sense of the translational potential of these approaches.

Do you have any advice for aspiring endocrinologists?

Follow your passion.

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You can attend Professor Mark McCarthy’s Dale Medal Lecture “Mining the genome for gold“ on Monday 14 November at 5:45 – 6:15pm.

Take a look at the full scientific programme for SfE BES 2022.

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Professor Anja Eckstein is an ophthalmologist specialising in orbital inflammatory disease. She is the head of the orbital centre of oculoplastics and orthoptic at University of Duisburg, Essen. In this interview she tells us about her academic inspirations, challenges in her field and what we can expect from her SfE BES lecture.

Tell us about your career so far?

I trained as an ophthalmologist at Moorfields Eye Hospital, University Eye Hospital in Tübingen and at the University of Duisburg-Essen. Currently, I’m head of the department for oculoplastic and reconstructive surgery, the orbital centre, and the orthoptic department at the University of Duisburg-Essen.  While in medical school I started research with a project on isolated retina and measured light potentials in different cell types with microelectrodes. So I started off my career in the field of medical retina but switched later to the ocular adnex disease, and the main clinical and research focus in Essen are orbital inflammatory diseases.

“The opportunity to exchange knowledge with the members of this research association has always inspired me, I especially enjoy the sense of humour of my British colleagues”

Who is your academic inspiration?

 I would like to give special thanks to my British colleagues. Participating in the EU INDIGO (Investigation of Novel biomarkers and Definition of the role of the microbiome In Graves’ Orbitopathy) project under the lead of Professor Marion Ludgate from the University of Cardiff was a particular academic inspiration. It was great to work with colleagues from many EU countries. I have been a member of EUGOGO since 2006 and the opportunity to exchange knowledge with the members of this research association has always inspired me, I especially enjoy the sense of humour of my British colleagues. A special mention goes to my excellent colleague Petros Perros from Newcastle. And, my colleague Simon Pearce whose work I admire in bringing new therapies to patients with autoimmune thyroid disease. I would also like to mention the always fruitful exchange with my colleagues in EUGOGO and ITEDS.

What do you enjoy most about your work? 

In our orbital centre we have many translational research topics that have a direct impact on patient care. We conduct molecular research on both in vivo and in vitro models of Graves’ orbitopathy. Here we look for new targets for therapeutic intervention and new possibilities for prevention. We also participate in phase 2-4 clinical trials testing new targeted therapies for patients with Graves’ orbitopathy. As a member of EUGOGO, I have also been able to take part in other clinical studies. The great thing about translational and clinical research is that the results go directly to the patient and improve patient care.

What are the biggest challenges your field faces?

We do research on rare, autoimmune diseases. Most research funding goes to oncology and cardiology, so it can be difficult to get funding for our research. Furthermore, a lot of the large companies who perform approval studies for drugs are mainly interested in common diseases, which can make it difficult for our field to secure support. For this reason, though, it is all the more gratifying that targeted blockade of the thyroid stimulating hormones (TSH) receptor by autoantibodies and small molecules is being researched through several therapy options.

What are the most exciting developments happening in your field?

Definitely the studies currently exploring the targeted blockade of the autoantibody-stimulated TSH receptor. If successful drugs can be approved here, it will prevent a series of painful and major surgeries in patients with Graves’ orbitopathy.

“The great thing about translational and clinical research is that the results go directly to the patient and improve patient care”

What are you presenting at your SfE BES lecture?

I will be giving a historical overview of milestones in Graves’ disease research, and illustrating the impact that these discoveries had on the care of patients with Graves’ orbitopathy. I will also be highlighting both the importance of both in vivo and in vitro models, since this is a focus of our molecular laboratory. Furthermore, I will address the new EUGOGO guideline for the treatment of patients with Graves’ orbitopathy, and the challenges of some new drugs being available in the USA but not yet in Europe.

Do you have any advice for aspiring endocrinologists?

As an ophthalmologist, this is a bit difficult for me. But in general I would recommend attending many international and national scientific meetings and cultivating exchanges with colleagues. You always get new ideas for work.

You can attend Professor Anja Eckstein, the 2022 British Thyroid Association Pitt-Rivers Lecture “TED/GO from bench to bedside“ on Wednesday 16 November from 8:30 – 9am.

Take a look at the full scientific programme for SfE BES 2022.

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Dr Maria Fleseriu is a neuroendocrinologist, she is Director of the Pituitary Centre and Professor of Medicine and Neurological Surgery at the Oregon Health and Science University in Portland, USA. Her work focuses on developing novel treatments for Cushing’s syndrome and acromegaly. Read our interview to learn more about her career path, what she loves most about her field, and a taster of her SfE BES 2022 lecture.

Tell us a little about your career path, so far?

I’ve always been fascinated with medicine. After learning how the heart’s mechanical valves and electrical system intertwined in the 6th grade, I became hooked. I would outline them on the foggy windows of my childhood home and my mum remembers how much work it was to clean the window smudges… After medical school, I trained in endocrinology in Romania, and subsequently completed another residency and then a fellowship at the Cleveland Clinic in the USA. I specialise in neuroendocrinology and currently hold two positions at the Oregon Health and Science University in Portland, USA.

Why did you choose to specialise in endocrinology?

During the first year of medical school, I became fascinated with the negative feedback system that regulates the hypothalamic-pituitary-axis. The fact that a pea-sized organ is the ultimate “master” gland intrigued me, so for my first research project I focused on improving imaging of the pituitary. This was the moment where neuroendocrinology became my passion.

Can you tell us about your current project?

My research focuses primarily on novel treatments for acromegaly and Cushing’s syndrome. I am also working to elucidate the extent and the recovery rate of pituitary dysfunction after surgical and/or other adjuvant therapies for pituitary adenomas. I have served as principal investigator or global principal investigator in multiple clinical trials studying novel chimeric molecules, new somatostatin multi-receptor ligands, adrenal steroidogenesis inhibitors, antisense oligonucleotide therapy and glucocorticoid receptor blocker use for the treatment of acromegaly or Cushing’s.

“I have great appreciation to the thousands of patients who have contributed time and energy for research studies, allowing us to better understand, and to discover new treatments for, this complex disease”

What do you love most about your work?

Although I’m no longer drawing on windows, I still get very excited about hormonal feedback! As the science and understanding of the pituitary gland improves, hopefully we will be able to diagnose pituitary conditions sooner. Early treatment could reduce complications and improve patients’ outcomes and I love to share the knowledge we’ve accumulated. When I saw my first patient with a pituitary tumour, almost 3 decades ago, all we had in terms of treatment was bromocriptine. We now have several classes of medications that we can use based on a “trial and error” approach, but personalised treatment regimens are increasing. I hope we will move closer to an individualised model, similar to that used in oncology.

What are the biggest changes in managing Cushing’s syndrome?

We face challenges at all stages, diagnosis can be difficult, especially in earlier, less ‘full-blown’ cases. The phenotype that we see is shared with several other conditions, which are much more common and necessitates physicians to be more aware of this syndrome, ‘to think about it’ and screen when needed.

Localisation can sometimes be challenging and the management itself can also be complicated, although we have better treatments, they don’t always work and recurrence rate in Cushing’s disease is quite high.

“Our mission is to educate our patients and medical community about hormones and promote innovative science – both of which will lead to better patient care. It is not easy, but it is fulfilling and rewarding”

Where do you see the next breakthrough happening in your field?

These are exciting times for specialists like me who have dedicated their career to the pituitary gland. Several histological and molecular markers have been developed that allow us to move translational research closer to the ‘clinic’. Physicians will soon have the right tools to predict the clinical course of pituitary adenomas more precisely and to develop individualised plans for management, also including patients’ preferences.

Could you tell us about your SfE BES 2022 lecture?

My lecture will highlight recent advances in management of Cushing’s disease, which should also consider comorbidities and complications associated that might compromise patient health and quality of life. I will discuss how treatments that specifically target certain pathways will create a paradigm shift in how we treat pituitary disorders, but WE ARE NOT THERE yet. I have great appreciation to the thousands of patients who have contributed time and energy for research studies, allowing us to better understand the aetiology and complications, and to discover new treatments for this complex disease.

Do you have any words of wisdom for future endocrinologists?

Pituitary disorders are complex and usually require a multidisciplinary approach. Every day, I communicate with a range of specialists, from neurosurgeons to gynaecologists, psychologists, and primary care physicians. While the hormones abnormalities are at the centre, they cause diverse health problems that warrant specific evaluation and management. Our mission is to educate our patients and medical community about hormones and promote innovative science – both of which will lead to better patient care. It is not easy, but it is fulfilling and rewarding.

You can attend Dr Maria Fleseriu’s Clinical Endocrinology Trust Visiting Lecture “Novel Approaches for Cushing’s Medical Management: Guidelines to Clinical Practice“ on Monday 14 November from 2 – 2:30pm.

Take a look at the full scientific programme for SfE BES 2022.