Spotlight on Dr Keith Siew, Research Fellow, Renal Medicine

Each month we will interview a member of DoM Staff. This week we speak to Dr Keith Siew, Research Fellow in Renal Medicine

12 June 2024

What is your current role and what do you enjoy most about your job?

I'm a Sir Henry Wellcome Postdoctoral Fellow co-leading the London Tubular Centre (https://www.londontubularcentre.org/) in the Department of Renal Medicine based at the Royal Free Hospital Campus, where we investigate the pathophysiology and aetiology of rare electrolyte and blood pressure disorders in wet and dry labs alongside our specialist clinics. It's been an absolute joy to help build up our incredible interdisciplinary team of clinicians, scientists and engineers. Nothing quite beats working with an enthusiastic creative bunch of people with a variety of disparate perspectives and skillsets. From the medics and their big picture ideas, often butting heads with the rigour and detail focused scientists, to the engineers who swoop in to point out the obvious practical solutions we missed (or to hold it all together with duct tape and a bit of string), there is never a dull moment and it makes the job exceptionally fun. It's only in teams like this that we get to realise real Bedside-to-Bench-to-Bedside research, and it's exciting.

What are you working on at the moment?

My usual bread and butter work, centres around the study of disease mechanisms, and looking at ways to explore some of the interesting cases that pop up in our clinics. And as my colleagues will tell you, I love my gizmos, gadgets and trying new shiny techniques. So in my time at UCL I've developed tissue optical clearing and volumetric imaging pipelines for VR-assisted 3D histopathology of human kidney biopsies, as well as new approaches to isolate and characterise urine-derived kidney tubule cells from rare disease patients for use on organ-on-a-chip microphysiological systems to personalise therapies.

However, the work that garners the most attention, without doubt, is my recent adventures into space medicine research. What started as a conversation over a bottle of wine, and a subsequent tipsy email to NASA asking if they had any spare kidneys, has turned into an over 2-year long UKSA-funded project examining over 53 omics, physiology and imaging datasets from some 20 independent cohorts of human astronauts, mice and rats exposed to spaceflight and space radiation experiments. It's the largest ever study into the health impacts of spaceflight on the kidney, and has involved working with over 100+ authors across 5 continents (and way too many time zones), and we're excited to be joining a paper package of nearly 50 space-health studies coming out in a special Springer-Nature collection later this year. The reception has been overwhelming, with some initial press coverage in the early days (https://www.theguardian.com/science/2022/apr/15/space-mice-may-offer-clues-to-why-astronauts-get-kidney-stones), and most recently being invited out to tour NASA bases and present the keynote lectures at their workshops (https://www.youtube.com/watch?v=alTAe0I53Uk).

But why look at the kidneys at all you might ask? Well as it turns out, astronauts have a significantly higher risk of forming kidney stones due to spaceflight, with over 30 documented cases in US astronauts in the months and years after spaceflight exposure. Indeed, one cosmonaut in the 1970s almost had to be emergency deorbited as he started passing a stone mid-flight! One part of our study sought to explain why this might be happening, as it can't simply be explained by excess calcium in the urine from bone demineralisation in microgravity? (Spoiler alert #1: the kidney structurally and functionally is remodelling). But the bad news doesn't stop there, as space is filled with stranger and exotic forms of radiation, namely galactic cosmic radiation, made up of particles like protons, helium nuclei and atoms of larger elements like titanium and iron travelling at near the speed of light blasted out of exploding stars in our galaxy. And as you can imagine this has some of the medics and scientists worried about long term risks for cancer, heart and brain damage. Surprisingly, despite the kidneys being extremely radiosensitive (e.g. the dose-limiting organ for total body radiotherapy) they haven't been on the radar of any space agency as a potential space radiation health risk, which was the 2nd part of our big study (Spoiler Alert #2: the kidney does not like space radiation at all!). So while I hate to be a buzz kill, it does seem like a trip to mars might have a few more hurdles than anticipated. (Check out a sneak peak at the rough draft preprint here if you can't wait for the package to be released: https://www.researchsquare.com/article/rs-2982830/v1)

What is your background and how did you find your job in this field?

I'm originally from Dublin, Ireland where I trained as an experimental physiologist-pharmacologist (BSc [Hons] - 2010) and advanced microscopist (MSc - 2011) at University College Dublin. For as long as I can remember I've always wanted to be a scientist (probably all the David Attenborough and National Geographic I was exposed to growing up), and I was very fortunate to have a loving family that nurtured my hunger to understand how the natural world worked. Through their support, and a chance meeting with my future PhD supervisor (Kevin O'Shaughnessy), I became the first of my family to enter a career in science.

In 2011, I undertook a PhD in medicine at the University of Cambridge (generously supported by the British Heart Foundation), where I published several papers on the mechanisms underpinning regulation of the blood pressure, arterial stiffness and renal tubular function in monogenic syndromes. In 2015, good fortune struck again, and while presenting my research at the American Society of Nephrology - Kidney Week meeting, I met Robert Unwin. A chance encounter that led to many subsequent fruitful discussions, culminating in a Sir Henry Wellcome Postdoctoral Fellowship in 2016. My original goal was to bring together old gold-standard techniques (e.g. renal micropuncture, microperfusion) with modern approaches (genetic engineering, intravital imaging, etc) to generate novel research tools to study the links between salt, diet and hypertension (i.e. high blood pressure). However, fate had other plans, and after a sabbatical (family, health and Brexit complications) I returned to the UK in January 2020 to take up my Wellcome Trust Fellowship, this time working with Robert Unwin's protege, (Stephen) Ben Walsh. Suffice to say the original plans I had for my fellowship got turned on their head by March of that same year, but it led to many more exciting opportunities I could have never dreamed of, so no regrets and 4 years on, I'm looking forward to the next step in my career!

What are your interests outside work?

Well I do love experimenting in the kitchen, being of mixed heritage I tend to chop and change between cooking Chinese-Malaysian food and some Irish dishes. It's always fun throwing a dinner party with friends and making up some new cocktails for the evenings' festivities. Otherwise, I very much take advantage of being in London and shamelessly go and see as many musicals, plays and live music gigs as my wallet will allow.