Interview with Stephen Chetwynd, Research Scientist

We sat down with Stephen, our Research Scientist, to learn more about the journey that led him to join the PlaqueTec team, and to highlight his role in the ongoing BIOPATTERN trial. Before joining PlaqueTec in 2024, Stephen completed a PhD at the Babraham Institute in Cambridge, where his researched focused on neutrophil-dependent immunity. After finishing his PhD, Stephen worked in a postdoctoral position at the Institute, where he collaborated with PlaqueTec to validate a drug target identified in PlaqueTec’s Clinical Study 1 trial.

Whilst not at work we learnt that in his free time, Stephen enjoys spending time with his family and doing things with his four- and two-year olds, which includes going on steam trains! He enjoys being active and cycles to work on Babraham Research Campus, where our team is based.

How did your professional journey lead to this role and working at PlaqueTec?

I studied for my undergrad degree in Manchester, where I started out doing biomedical science but ended up as a cell biology graduate. After university I applied for a PhD that I was really keen on pursuing, however, the feedback at the time was that despite being passionate, I needed to get some lab experience as the people I was up against had a lot more than I did. So, I followed that advice and got a job with AstraZeneca, which at the time was based in Manchester. I worked there for a couple of years in quite a few different roles and got valuable practical insight in high throughput screening and high content imaging-based technologies. It was a great opportunity for me to get different experiences which enabled me to work out the bits that I enjoyed most.

A few years after joining, Astra Zeneca moved to Cambridge which led me to move down here as well. I started a completely different role focussed more on molecular biology, working with CRISPR technologies and engineering cellular models. Although I was very much enjoying it and AstraZeneca was a great place to work, I felt I’d reached a ceiling and realised that maybe it was time for me to do my PhD. I applied for a position in Cambridge and ended up working at the Babraham Institute in Heidi Welch's lab where I was studying the roles of an immunosuppressive protein in neutrophils. It was during my PhD that I first met Simon and Diane at PlaqueTec (Dr Simon Williams, General Manager and Dr Diane Proudfoot, Chief Scientific Officer). Diane and Heidi already had a good connection, having worked together previously at the Babraham Institute, and towards the end of my PhD PlaqueTec formed a campus collaboration with the Welch lab. I started a postdoc at the Babraham Institute immediately after my PhD in this collaboration with PlaqueTec, where my role was to test identified compounds for one of the interesting targets that PlaqueTec had discovered in its Clinical Study 1 trial. The collaboration went very well and after my postdoc, PlaqueTec took me on as a research scientist to pursue this target further and to support the scientific programme.

What problem is PlaqueTec working to address?

Coronary artery disease (CAD) is the leading cause of death worldwide yet we still struggle to predict which patients will progress to more serious cardiovascular events and why. At present, most patients with CAD receive broadly similar treatments such as lipid lowering therapy. Although these treatments are effective at lowering these lipids, a lot of patients still progress to have serious cardiovascular events. We are trying to find ways to tackle this gap in our knowledge and identify some of the biological drivers at the level of the coronary arteries themselves. By combining intracoronary sampling with omic technologies and our cell phenotyping data, we aim to uncover specific biomarker patterns that can guide more personalised diagnosis and treatment.

Can you tell us a bit about your involvement in the BIOPATTERN trial and what a day in your role looks like?

My main role in the BIOPATTERN trial is cell immunophenotyping, where I carry out flow cytometry on the participants’ blood samples. Our 30 plus colour panel utilises spectral flow instruments, enabling us to take whole blood and look into the relative proportions and activity status of 30–40 different cell types per patient. From the trial, we have multiple samples per patient, representing both peripheral blood and blood from within the coronary arteries themselves, so we're able to see which cell types are enriched at the site of disease. This allows us to pinpoint which patients have altered levels of certain immune-related cell types at the disease surface.  Integrating this with our other data modalities allows us to begin to understand the mechanisms underlying the biosignatures we’re observing.

Although flow cytometry was a key technique during my PhD, experiments required only a relatively basic application of the technology. PlaqueTec’s immunophenotyping is significantly more complex, and the extensive practical and theoretical training I received from the Babraham Flow Cytometry Facility has enabled me to confidently lead this aspect of the project after an earlier collaboration between PlaqueTec and the Flow Cytometry Facility had established this new approach.

Another major role for me in the BIOPATTERN trial is assisting with blood sample management, from aliquoting and safely storing plasma samples to performing important quality control assays on the samples, such as haemolysis checks.  These technical activities require full days working in the laboratory followed by some data analysis.

I also support PlaqueTec’s science programme in a variety of other ways, such as literature reviews on the most promising signals for druggability potential, assisting with research into emerging technologies that could apply to PlaqueTec’s samples, and I enjoy collaborating with our data scientists who are building BIOCARTA®; our database which handles the different data modalities.

One of the things I am excited about in the near future is a role I will have in validating some of the new targets identified from the BIOPATTERN trial. The plan is to test several targets, performing in vitro experiments to derisk a potential future drug development programme.

What inspires or motivates you about PlaqueTec’s approach to understanding coronary artery disease?

What is really unique about our approach is the types of samples we have. The majority of studies in CAD analyse blood samples from a peripheral source, but any signals coming directly from the disease will have been diluted throughout the whole body by the time you collect it. Our site-of-disease samples come from the exact microenvironment where the disease exists. This means we have the potential to have an edge on getting the most relevant signals possible. We've invested in getting brilliant technologies to extract as much information from those samples as possible. It is the combination of these factors with our unique samples that gives us a really good opportunity and chance of genuinely making advancements in CAD precision medicine, which is incredibly motivating.

PlaqueTec is based at the LiveLabs on the Babraham Research Campus. What do you enjoy most about this co-working lab space?

It's a very collaborative environment and is perfect for smaller companies. There's a shared lab space and people are very conscious of each other. There are also opportunities and grants available to collaborate with other companies. We've had some interesting talks with people over the last year or so and had some potential early stage ideas to utilise some of the other expertise there. One of the other things that's great about working on the Babraham Research Campus is the access to state-of-the-art equipment and expertise that go with it. The Flow Cytometry Facility in particular has been instrumental in our success in optimising our spectral flow experiments.

One of the nice things about coming from the Institute and now being based in LiveLabs is that I still have those connections. There's that kind of nice aspect of having your shoe in both areas.