Researcher Spotlight: Professor Graham Williams
Graham Williams is a Professor of Endocrinology at Imperial College London. Funded by a Wellcome Trust Strategic Award, his research involves looking at the connection between hormones and bones, with the hope of identifying new drug targets to enable the development of new treatments for people with debilitating bone and cartilage diseases. We caught up with him to find out more about his research, and what it was about science that persuaded him away from a potential career as a detective…
What are you working on?
I’m lucky to work on two things that really fascinate me – hormones and bones. It all started when I focused my studies on the mechanism of thyroid hormone action to investigate how thyroid hormones control skeletal development and regulate the maintenance of bone mass and mineralisation.
My fascination with regulation of the skeleton has diversified so that we are now phenotyping knockout mouse strains generated at the Wellcome Trust Sanger Institute as part of the International Knockout Mouse Consortium. This is a large international undertaking as we are developing novel imaging and functional approaches to phenotype more than 1500 knockout mouse lines.
The aim is to identify new genes that specify bone and joint structure and function, and provide new disease models for skeletal disorders. We are using RNAseq and bioinformatics approaches with collaborators in Australia to uncover new signalling pathways that underlie disease pathogenesis.
What does your average day involve?
The majority of my time is devoted to research, but I also have the privilege of looking after patients and can relate my research directly to human physiology and disease.
Some of my time is devoted to writing manuscripts and grant applications; two ends of a satisfying spectrum. Publishing a paper represents the culmination of a vast amount of hard work and dedication for many people, whilst writing a grant application offers the opportunity to think about new scientific questions and develop hypotheses. A particular joy for me is to discuss these questions with my closest colleagues; we work out our ideas and plans – collaborative working is synergistic, immensely powerful and great fun.
I also spend a lot of time going through experimental data with the post-docs, students and technicians working in the lab. I like to do this on an ad hoc basis whenever I can, but we also have more formal lab meetings so that everyone is able to talk about their work and get ideas and suggestions from the rest of the group. These sessions are diverse, often lively and always entertaining.
Sometimes I even get a chance to get into the lab and play with the microscopes or do some bench work. Sadly my time in the lab is limited and gets less and less, much to the relief of the post-docs and students!
Why is your work important?
Bone and cartilage disorders affect millions of people. For example, it is estimated that an osteoporotic fracture occurs every three seconds – with one in three women and one in five men over 50 being affected. Similarly, up to one in five women and one in ten men over the age of 60 will suffer from osteoarthritis.
There is an urgent need to improve understanding of the causes of bone and joint disease, and identify new disease models to develop better treatments and new approaches to prevent disease progression.
What do you hope the impact of your work will be?
Better and more detailed understanding of bone and joint pathophysiology leading up to the identification of new and specific drug targets. Ultimately, this should translate to new preventative treatments for debilitating diseases that have such a major impact on individual patients as well as on society at large.
How did you come to be working on this topic/in this field?
As a medical student at St. Thomas’s I loved anatomy and did an intercalated BSc. Part of this included studying fossils and human evolution and so I developed a fascination with bone. I also got hooked on negative feedback loops in physiology so when I started my clinical studies it was no surprise to enjoy endocrinology – I love the investigative challenge and at one time even considered a career as a detective!
I decided to specialise in endocrinology, but always knew research was what I really wanted to do. After my PhD studies in Birmingham I had the chance to go to Harvard Medical School in Boston to work on the regulation of gene transcription by thyroid hormones. When I was about to leave Boston I was urged to identify a new topic for my own research.
It didn’t take long to realise that nobody at the time was working on the role of thyroid hormones in bone, even though links between thyrotoxicosis and osteoporosis had been known for more than a century. On the plane back to England I became convinced this was the field for me; it’s amazing how the topic has grown and where curiosity can take you!
How has Wellcome funding helped you/your research/your career?
Wellcome Trust funding has been crucial. I have been lucky enough to obtain substantial funding over the years from the MRC for my research in endocrinology. Alongside this support, additional grants from the Trust have allowed me to develop new ideas and new experimental approaches, and these have enabled us to turn the focus of the lab more generally to the skeleton.
With the help of a Wellcome Trust Strategic Award we now have state-of-the-art rapid-throughput skeletal phenotyping capability that incorporates light, confocal and back-scattered electron scanning-electron microscopy, high-resolution micro-CT and mechanical testing. Without the Trust’s vision to push the boundaries none of this would have been possible, and I think we are now at an exciting time of discovery.
What’s the most frequently asked question about your work?
The two most common questions I am asked are: “What is a knockout mouse?” and “What is endocrinology?” I usually get asked these when I am on the golf course at a critical stage of a match!
Which question about your work do you most dread – and why?
I don’t really dread any specific questions because people are genuinely interested.
Tell us something about you that might surprise us…
I love sport and cycle to work every day (15 years and counting). I play golf as much as I can, now that being competitive at football is unrealistic! My personal luxury is a love of Church’s shoes; I have several pairs and wear them every day!
What keeps you awake at night?
Not too much really, although from time to time I wake up in the middle of the night with an idea that seems to have come from nowhere. Sometimes the idea makes it into an experiment!
What’s the best piece of advice you’ve been given?
I vividly remember my primary school headmaster in one school assembly tell us that “it doesn’t matter what someone does or is good at, but it does matter that you make the most of whatever talent you have”. My parents brought me up with the same values and have always encouraged me to do what I enjoy the most. To have had that opportunity is the thing I value the most; I have been very lucky and cannot thank them enough.
You can find out more about Professor Williams’s work and publications here.