Interviews with Scientists: Stuart Maudsley
In our latest Interviews with Scientists, we talked to Stuart Maudsley! Stuart is the Group Leader of the Translational Neurobiology Group and Adjunct Department Director of the VIB Center for Molecular Neurology at the University of Antwerp. His research focuses on the age-dependent changes in receptor pharmacology associated with neurodegenerative conditions such as Alzheimer’s disease and Frontotemporal dementia.
After gaining his PhD as the Ackroyd Brotherton & Brown Research Fellow in Receptor Pharmacology from the University of Leeds, Stuart received a Howard Hughes Medical Institute Fellowship to train with Professor Robert Lefkowitz (2012 Nobel Laureate in Chemistry) at Duke University. He was then recruited to be Principal Investigator of the Receptor Biology Section at the Medical Research Council Human Reproductive Sciences Unit at the University of Edinburgh in the UK.
After successfully developing a line of receptor-based novel prostate cancer therapeutics at the MRC Stuart was then recruited by the United States National Institutes of Health (NIH) where he worked for the next decade as the Head of the Receptor Pharmacology Unit at the NIH-National Institute on Aging at Johns Hopkins Medical School.
We spoke to Stuart about his research, the current challenges faced by life scientists, and advice he’d give to those just starting out in their scientific careers.
Hi Stuart! Firstly tell us a bit more about your career so far...
I studied Pharmacology as an undergraduate at the University of Leeds, then went on to do my PhD there, focusing on G protein-coupled receptor (GPCR) activation mechanisms. During my PhD I became increasingly interested in the field of GPCR signaling theory and how this could be used to design more effective drug therapies. When I was writing my PhD thesis I kept reading papers by this guy in America, Bob Lefkowitz. His work and mine seemed to be heading in the same direction, looking at GPCRs as functional systems that can be measured and rationally exploited.
When I finally finished, I applied to his lab for a post-doctoral fellowship – and after a very nerve-wracking interview I was able to consider Bob as my postdoctoral mentor. In his lab at Duke University I was in the company of a plethora of amazingly talented and super-hard working fellow scientists. For my fellowship I continued my work on GPCR signaling, and during this time we found out that what we considered to be the GPCR (i.e. the seven transmembrane heptahelical core) was just a fraction of the real functional drug target he had discovered a few decades before.
At Duke I was also fortunate to meet another of the most important scientific mentors in my life, Dr. Louis Luttrell, who taught me how to deal with the day to day rigors of science. To this day I consider both Lou and Bob as vital friends in my scientific career. After this training phase of my career I held Principal Investigator positions at the Medical Research Council/University of Edinburgh, the National Institutes of Health/Johns Hopkins University and now as Vice-Chair of the Department of Biomedical Science and the University of Antwerp.
I’ve made many lousy decisions as a scientist (I think everyone in biomedical science can attest to this) but deciding to focus my career on the investigation of GPCR signaling has been the best decision I made. Working with GPCRs has allowed me to understand the mechanistic intersections between physiology and pathophysiology in a broad spectrum of clinical settings such as nociception, cardiovascular science, reproductive biology, molecular gerontology, diabetes and metabolic disorders, neurodegenerative disorders and psychoactive disorders. GPCRs are really the prototypic biological ‘nanomachine’ that controls nearly every aspect of biology – my fascination with them is limitless, I think we’ll always only know about 10% of their true biological capacity.
What's the main research focus of Maudsley Lab?
Our lab aims to develop a highly nuanced understanding of the cellular signaling pathways that control the generation of complex age-related diseases. Hyper-complex events such as aging, while being amazingly intricate, are still controlled in an organized manner by what we term ‘Keystone’ proteins that exert a master regulator effect over multiple signaling systems. We aim to employ GPCR-targeted therapies to control these hyper-complex biological events through a specific control of these ‘Keystone’ proteins.
What's your team's particular research focus at the moment?
Our lab currently investigates the role of multiple GPCRs – and their associated signaling systems – that control various pathological aspects of the aging process. In our lab we believe that many of the most prevalent disorders today, such as cardiovascular disease, metabolic disorders, and dementia, are all strongly controlled by signaling mechanisms that we have classically associated with the aging process.
Aging itself is not really a specific disease, but the acceleration of cell signaling pathways that control the accumulation of lipid peroxidation, protein misfolding/aggregation and DNA damage augments the presentation of aging pathologies including atherosclerosis, dementia, neurodegeneration, and muscle weakening. So, our approach is to identify the key proteins that control pathological aging signaling networks, then identify the GPCRs that can regulate the expression of these proteins – and thus slow down the rate of age-associated damage, and thus reduce the development of age-related disease. With this strategy we think that we can treat multiple disorders by hitting just a small number of therapeutic targets.
You recently hosted the first ever Pint of Science event in Antwerp, how did you get involved with them? And how did you find the experience?
Yes, Pint of Science in Antwerp was a great success, we sold out all of our events. I had been following how Pint of Science was going down (pardon the pun) in the UK and other countries, and together with two great colleagues at the University of Antwerp, Drs. Bronwen Martin and Michele Giugliano, we wanted to set up our own event to bring our research to the people that matter – the public. Our ‘Beautiful Mind’ event spread over three days, and contained some fascinating and friendly talks from some of the best neuroscientists here at the University. It was great to see such a diverse audience enjoying the evenings – we had attendees aging from 5 to 75! I enjoyed the experience so much, as it was such a fun contrast to the daily process of science in the lab.
Why are science events like this, which are open to the public, so important?
I think they’re important for two reasons – firstly it’s so important for the integration of science in our popular culture that talented and enthusiastic scientists can easily mingle and discuss their research with the people that pay for it and will eventually benefit from it.
Secondly I think that it’s a wonderful experience for the scientists themselves as the act of science communication itself helps us to better understand the relevance of what we do and really helps us come up with new ideas and insights – inspiration can come from anywhere and getting fresh new perspectives is invaluable.
Did you always want to be a scientist, and made you want to pursue a career in your particular field?
When I was young, like many kids I wanted to be an astronaut. I dreamed of being the first person to set foot on Mars! It was a big dream, but then you have to dream big. I think I wanted to do it as I have a burning desire to be the person that pushes the envelope, expands our human experience, and helps inspire others to reach their greatest limits. Now I run a biomedical science lab but on a daily basis we are lucky to be the first people in the world to see and discover new molecular signaling mechanisms that could form part of drug strategies that could help the world. In this way, on some days, members of my team are putting their first foot on Mars, just in a different way!
I have really loved pharmacology as I see it as a wonderful opportunity to blend many different types of scientific interest: medicine, chemistry, biophysics, mathematics and computation. I feel that biomedical scientists of the future should be multidimensional (just like the age-controlling factors we work on) as this allows great collaboration, the fueling of truly novel ideas, and also an exciting and diverse work environment.
What do you think are the biggest challenges currently facing life scientists and their work at the moment?
I would say the biggest challenge in biomedical science is trying to reverse the damage done to research by the current model of endlessly cycling research-paper-grant. This creates a field that essentially is self-serving and ever more removed from the process of reaching an important and translatable goal for patients. Put simply, research is too often rewarded for competence rather than importance. This then gets reinforced by the concept of ‘Impact’ in which the number of citations one’s published manuscript receives, in journals that almost 90% of the general population never read, are used as metrics of performance and quality.
Therefore as long as the research is published in ‘High Impact’ journals then it is considered important and more funding is channeled there – there is very little importance placed however on an ‘end-product’ that is effective for healthcare workers or patients. Unfortunately this process also reinforces competition rather than collaboration between scientists as only two authors receive credit for the work: the first and the last. Hopefully there may be positive changes happening soon, especially if more scientists are committed to proposals such as SFDORA (the San Francisco Declaration on Research Assessment). SFDORA aims to break down the biases of traditional scientific paper reliance in science, academia, and publishing by championing the actual content of papers and not obsessing which journal the data is published in.
Biomedical science needs to be more bold and focused on ‘Grand Projects’ (such as Large Hadron Colliders or even Moon Landings) that create a tangible outcomes that truly impact our society and also involve real collaborations between ethical and passionate scientists.
What advice would you give to someone just starting their life science career?
Always look to the future. Science is evolving at an incredible pace now. Much of the work we do in the lab now will be performed in the future by AIs and robotic automation. Therefore I always enthuse my students and staff to work on their creative thinking skills – some people are born with this as a gift, but creativity is definitely an aspect of your character that can be improved.
It is also incredibly important to be flexible, choose a path or career that will allow you to expand and develop in different ways, and focus on the concepts and not the techniques, as these will change on a year to year basis. Also, find something you love that excites you when you work and also fires you up when you present it! I have been lucky that I found my topic of GPCRs early on in my career, it has been a fantastic journey of discovery for me.
Outside the lab, what do you enjoy doing?
In this day and age time outside the laboratory gets less and less each year. When I do get time however there’s nothing more I enjoy more than spending time with my wonderful wife and my three fantastic children.
If you weren’t a scientist, what do you think you’d be doing?
I would be an artist. Science and art are so close as disciplines, creativity and imagination are key to both. Great science and great art are always beautiful and nature has ensured that the best biomedical mechanisms are always, efficient, effective and elegant. I love this theoretical symbiosis between art and science.
Which scientists working today do you most admire, and why?
The scientists that I admire most in the world are those that conduct science to the very best of their ability, solely for the cause of improving the lives of others. Selfless, dedicated scientists – many of whom are never known – form the cornerstone of our research community. We need more people that put their passion for their work over their personal gain.
What’s your favourite science quote?
At our Pint of Science recently I used a great one from Linus Pauling, it sums up my scientific method as well: “If you want to have good ideas, you must have many ideas”.
What do you think is the greatest scientific discovery of all time?
You’re going to hate this, but to answer that question will elevate one discovery (and a small number of scientists) above others and I think that sort of discussion is one of the things that holds science back.
We all know the ‘big and great’ discoveries and scientists but science is part of us all and should be shared by us all. Perhaps then the greatest ‘discovery’ really is our ability for teamwork – this is what really created all those world-changing findings.
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Thank you so much for talking to us Stuart, and we don’t hate your answer to the last question at all, it’s a brilliant response!
Here’s how you can connect with Stuart online:
Keep up to date with Stuart’s lab on Facebook here
Follow him on Twitter
Check out his university staff profile
Follow his work on ResearchGate
Connect with him on LinkedIn
Find his latest research on Semantics Scholar
