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Brainwaves: Interview with Professor Waljit Dhillo

Brainwaves: Interview with Professor Waljit Dhillo

Interviewing eminent neuroendocinologists about their work, passions and tips for budding scientists.
Interview by Agnes Becker, BSN Communications Officer.

Waljit Dhillo portraitWaljit Dhillo is a Professor in Endocrinology & Metabolism, Consultant Endocrinologist and an NIHR Senior Investigator at Imperial College London, UK. Waljit held the Clinical Liaison position in the BSN Committee from 2013-2021. In this interview, Waljit tells us about why basic science is so important in finding new therapies, why in-person conferences are best for new ideas and forging interdisciplinary collaborations and why he feels like a child in a sweet shop when it comes to work!

1. Tell us about your research and why it excites you

My research is on neuroendocrine control of reproduction and metabolism. The reason it excites me is because it’s using science to understand major medical problems. New breakthroughs in treatments only come if we understand the science.

One of the things that we came across almost by serendipity was neurokinin B in menopause. Menopausal flushing is due to low oestrogen. It affects millions of women across the world and HRT is effective but for many women it is contra-indicated due to the risk of breast cancer etc. The reason we hadn’t moved on in the field is because there have been lots of other drugs that have been tried, but if you don’t understand the physiology – low oestrogen causes the flushing but what’s the black box in the middle? - you don’t know the treatment.

To cut a long story short, a basic science researcher in the States (Prof Naomi Rance) developed a rat model of menopausal flushing. Over a 20-year period she unpicked the exact mechanism that she thought was causing the menopausal flushing in a rat, which was neurokinin B (NKB). NKB acts on the NK3 receptor, so the obvious thing is what if you block that receptor in menopause, what happens? What you get is a 73% reduction in flushing in post-menopausal women. That treatment is now in phase 3 trials and a treatment should be available to patients worldwide in the next couple of years. Without that science we wouldn’t have that breakthrough. That is the most exciting thing – using the science to understand the physiology and, if you can do that, you can generate new therapies for patients.

2. What inspires you most in forming new research ideas?

This is where COVID has hit us quite badly through lack of research meetings. Being aware of the literature is helpful but discussions at meetings and hearing someone’s new data is needed. For example, the story above was presented at a meeting in Tokyo in 2012. The paper hadn’t been published and I might have missed it if I hadn’t been at that meeting attending a talk I was interested in. So going to meetings and talking to people and forming collaborations is something we have really missed. I don’t think online meetings work very well. Meetings are more about the people, collaborations and ideas. The best collaborations I have developed have been at dinners after the talk which you don’t get online. You probably won’t give your best ideas in a Zoom call but you may mention them in the corridor after a talk. With Zoom you’re booked one meeting after another and there’s no time to think but when you’re away you can’t do any other meetings as you’re physically away thinking about nothing else other than the meeting.

3. What’s been your most important or surprising finding?

It was a surprise to me that a single molecule which blocks the NK3 receptor could have such a big effect on reducing menopausal vasomotor symptoms. I suspect there are 10-15 other pathways mediating low oestrogen causing flushing but the NKB/NK3R pathway appears to be the major efferent pathway that the others converge on to mediate menopausal flushing. People say why do you need basic science if it’s all about translation? You won’t get the translation if you don’t have the basic science. You can’t do these studies on humans - I don’t think many people would be willing to have their brain regions knocked out! While many animal models aren’t ideal, they often do give us the answer for human translation.

4. What’s it like being in between the clinical application and the research?

It’s a challenge to keep up with both, but it’s exciting! In terms of the medical challenges it’s easier to see what the problems are facing patients because you’re seeing patients in your daily work. We can carry out animal and human studies in my lab so being able to translate to humans is really exciting because you’re doing the basic science and moving it downstream. If you publish a paper and it never goes anywhere it’s good for your career and it’s fun but in terms of making a difference translating what we do is really important.

5. What qualities do you need as a person to be able to work in translational research?

Research training – a PhD is a minimum - and new ideas rather than only healthcare delivery. I enjoy my clinical work but if you can make a difference to millions of lives with a new therapy from your research, that has a huge impact beyond the patients you can see in your career.

6. Describe a typical pre-COVID day and how it’s changed since the pandemic?

I haven’t really got one! That’s what is exciting about being a clinical academic. If I’m on the wards I’m seeing patients, doing ward rounds, doing clinic, managing junior staff – those shifts are non-negotiable. But if I’m on the research side my diary is completely random. I have meetings with trainees – I’ve recently been appointed to a national training role as Dean of the NIHR Academy which is really exciting as it involves leading training of the next generation of healthcare researchers – research meetings with my team, and I’m Head of Division at Imperial so there’s those meetings too. I have a very organised PA who helps me with my diary! But the most enjoyable bits are seeing my patients get better, the research and training the next generation. With COVID, luckily the research facility we have is part of the hospital, but in a safe environment so we have been able to carry on apart from when we have been needed on the frontline in the first pandemic when my team and I voluntarily returned full time to clinical care. We’ve been doing more online meetings than face-to-face, which is good in some cases such as transferring information, but not good for ideas and new thought processes.

7. What methods does your lab specialise in?

We have abilities to do in vivo animal physiology all the way up to human studies, clinical trials and functional MRI studies in humans. That means rather than having one focussed research area we have the ability to harness the different research questions that come up, which is exciting.

8. Who or what inspired you into neuroendocrinology?

I trained at Barts which has an excellent endocrinology centre. When I was training as a student I was inspired by the big players in endocrinology at Barts such as Professors Mike Besser, Ashley Grossman and John Wass. I really enjoyed biochemistry and physiology so the two came together very well. I like pathways, how things work and being able to make a difference.

9. How has the British Society for Neuroendocrinology impacted your career?

The BSN has been a great forum in my career. I like the small community of the BSN as you get to know a lot of the members at the annual meeting who are colleagues and soon become friends. A lot of collaborations have come from the BSN – we’re meeting Kevin O’Byrne’s team this afternoon for a 3-4 hour lunch as we have joint grants and papers – and that’s come from the BSN through the committee and council of which I’ve been part. I think the collegiate nature and the family atmosphere makes it a really nice community to be part of. Everyone gives their time for free so the money from the journal can go into the research and importantly to support early career researchers.

10. What do you value most about the Journal of Neuroendocrinology?

The journal is the flagship for the Society and is a good home for publication of neuroendocrine research and now we have the translational element as well we have a repertoire of basic and translational research. It allows us to give travel grants and give back to the community so that’s great. Without JNE the Society wouldn’t be flourishing as it is.

11. Which other areas of research do you find particularly exciting at the moment?

All areas are exciting! But for my research it’s AI and mathematical modelling. We have developed new collaborations in both of these areas. We have done basic statistics on all the hormones that we measure in our clinical studies but if you work with people who do mathematical modelling you get more out of the data. We have a PhD student specialising in AI and a mathematical modelling team in Exeter who specialise in hormonal modelling – another collaboration that came from a meeting that led to grants together. Those collaborations in new areas are really exciting. We’re also working with our chemistry colleagues to develop an aptamer to get an instant read out of hormones. New technologies that you can apply to your research are really impactful.

12. What advice would you give an aspiring neuroendocrinologist?

Follow your passions and dreams. Life is about having fun as well as working hard. If you’re enjoying what you do, you’re having a great time! I see myself like a child in a sweet shop – I’m doing something I enjoy and getting paid for it! and hopefully making a difference for patients.

13. What do you hope your academic legacy will be?

Two things – making a difference to patients and inspiring the next generation of academics because if you don’t do that, research ends. It would be great if my research leads to new therapies based on kisspeptin and neurokinin B available in the clinic, which could transform the lives of patients with reproductive disorders - that would be wonderful.