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Meet the Early Career Researcher prize winners for 2020

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Published: 24 Mar 2021

Each year the British Journal of Pharmacology (BJP) and the British Journal of Clinical Pharmacology (BJCP) award prizes for the best paper published by an early career researcher in the journals over the previous year.
 
In 2020, the winner for BJP was Yi Wang (YW) of Zhejiang Chinese Medical University, for Structure‐based discovery of CZL80, a caspase‐1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility and for BJCP, Kevin O'Gallagher (KOG) of King’s College London for Grapefruit juice enhances the systolic blood pressure‐lowering effects of dietary nitrate‐containing beetroot juice.
 
We interviewed our winners to find out more about their work, careers and interests.


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Yi Wang (left) and Kevin O'Gallagher (right)

What excites you about pharmacology?

YW: I consider pharmacology an interdisciplinary science with two important goals. One is to reveal the mechanisms of diseases to identify drug targets. The other is to find promising drug candidates and study how the drug will work and fight against disease. To achieve these goals, pharmacologists need to draw on knowledge from multiple disciplines including physiology, pathology, medical biology, biochemistry and even materials science.
 
KOG: I have always been impressed by the breadth of research opportunities on offer in pharmacology – there is something for everybody. 

What are the key points of your article and their implications?

YW: In our study, we demonstrated that caspase-1,an enzyme that cleaves precursors of the inflammatory cytokines interleukin 1β, is essential for the generation of febrile seizures. We also screened a small-molecule inhibitor of caspase-1, CZL80, which significantly reduced neuronal excitability and reduced febrile seizures in neonatal mice, and relieved the enhanced epileptogenic susceptibility in adult mice. As caspase-1-mediated neuroinflammatory signaling is shown to be involved in the pathophysiology of epilepsy, our caspase-1 inhibitor may be therapeutically promising for the treatment of drug-resistant epilepsy. 
 
KOG: It is well established that dietary nitrates -for example, those found in beetroot juice- decrease blood pressure via the inorganic nitrate-nitrite-nitric oxide pathway. We found that adding golden grapefruit juice to beetroot juice enhanced its ability to lower blood pressure. The mechanism behind this effect appears to be more complex than we expected and therefore will be explored in detail in future studies.
 
The knowledge that it is possible to enhance the effects of dietary nitrate on blood pressure could help to maximise the clinical benefits of dietary interventions for some medical conditions. The fact that pulse pressure was improved is interesting, as it is highly prognostic for adverse cardiovascular events. 
 
The benefits of dietary nitrate are being investigated in other areas (such as exercise performance and heart failure) and there is also the potential to explore whether the enhanced beneficial effects we saw in our study could work in these areas.

What are you currently working on? Take us through a typical day in your life

YW: I am currently focusing on the molecular/circuitry mechanism of epilepsy and the development of novel therapeutic approaches or drug targets for epilepsy treatment, by using optogenetics, multiple-channel EEG analysis, imaging, electrophysiological and molecular techniques.
 
Usually, I begin my day with breakfast with my family. Then, I drive to work and spend my whole day in the lab. My work includes carrying out experiments, data analysis and manuscript writing. At night, I spend 1-2 hours exercising in my home gym, then, I check for, and read, new literature on topics relevant to my work.
 
KOG: Perhaps unsurprisingly, both my academic and clinical working life is dominated by COVID-19 at present. In addition to keeping my MRC-funded PhD project running as much as the pandemic allows, I have used the opportunity to get involved in COVID research.  Early in the pandemic, there was concern that ACE inhibitors might leave patients more susceptible to severe COVID-19, due to the SARS-CoV-2 virus using the ACE2 receptor to enter cells. Working with the amazing King’s College London bioinformatics team, we were one of the first groups to publish data to suggest that ACEi and ARBs are indeed safe and not associated with any increase in mortality. We have also completed work on other important COVID-related topics including cardiovascular complications and the effect of ethnicity. Clinically, we reported the first case of cardiac tamponade secondary to COVID myocarditis. We had to perform an emergency pericardiocentesis in an ICU side room, which was one of the more stressful moments of my career to date!
 
I have also had the chance to see research from the other side, as a participant in the Novovax COVID-19 vaccine trial (NCT04583995). 

What are the biggest challenges you’ve faced?

YW: The biggest scientific challenges for me are when you have a big question but no suitable solutions or exact answers. For example, how to achieve the goal of precise circuit-based drug development is still a big and complex puzzle. We have been working on this topic for the last five years.
 
KOG: When I think about the challenges in my career, I think back to the process of applying for PhD fellowships. I had a few unsuccessful attempts before finally getting my MRC Clinical Research Training Fellowship. I particularly remember receiving a rejection that essentially read ‘please don’t reapply’. I was on holiday in France at the time and it really put a downer on the trip. I am glad I had the support and guidance from my supervisors, Dr Andrew Webb and Professor Ajay Shah, who encouraged me to keep working to strengthen the application. In retrospect, although it was a difficult time professionally, the critical feedback from grant reviewers helped me to improve the project and the work involved led me to a greater understanding of the research area. I think the two lessons are 1) keep working toward your goals and 2) don’t check work emails when on holiday!

What do you enjoy doing outside of work?

YW: During my spare time, I enjoy my time with my family. I also enjoy many kinds of exercise, though basketball is my favorite and I am a member of the staff basketball team in our department. Usually, we have two weekly training sessions.
 
KOG: At weekends, nothing beats going for a long walk on Wimbledon Common with my wife and our springer spaniel. I am also a keen runner, taking part in anything and everything from track races to ultramarathons and mountain races. 

What’s next for you, and what do you hope to achieve over the course of your career?

YW: I am a young researcher in Zhejiang University and my career has only just started. In the future, I hope I can provide students with a high standard of pharmacology teaching. I also hope that my lab will be a good place to help students do enjoyable research. Finally, as my personal research interests lie in epilepsy, if I am lucky enough, I hope we can develop novel therapeutic approaches or drug candidates for epilepsy treatment, which can be translated into clinical applications.
 
KOG: My MRC Clinical Research Training Fellowship comes to an end this year. After that, I will be finishing my interventional cardiology training and applying for future clinical-academic funding.
 
Having had the opportunity to set up a small clinical trial as part of my MRC fellowship, it would be great to get involved in planning and running larger therapeutic trials in the future.
 
I have also been fortunate to receive some fantastic mentorship from my PhD supervisors and others over the past few years and I hope that over the course of my career I might be able to provide the same level of support and advice to others.

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Published: 24 Mar 2021

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