Detecting cancer early, together

Every week, in his role as a clinical geneticist at Addenbrooke's Hospital, Joe meets patients and families who know they are at high risk of developing cancer. Their questions are urgent and deeply personal: when will it happen, and can anything be done to stop it?

Some of the answers may lie hidden in cells that look completely normal. By studying the earliest genetic changes – long before disease takes hold – the team’s work, led within the Rahbari group, aims to uncover these invisible clues and explore whether cancer can be detected, and even intercepted, earlier than ever before.

In this blog, we sat down with Joe to talk about his work at Sanger, what drives his research and why he believes you should never go it alone.

I’m an academic clinical lecturer – something of a misnomer, as I only give a couple of lectures a year! I’m employed by the University of Cambridge in the Department of Genomic Medicine, which supports half my time, while the other half is dedicated to my clinical genetics training. Alongside this, I work within the Rahbari Group at the Sanger Institute, where most of my research takes place, with links back to Cambridge, working with Professor Marc Tischkowitz and other collaborators.

NIHR Clinical Research Facility: Cambridge at Addenbrooke’s Hospital (Left to right: Lori, Areti, Sherly and Dr Joseph Christopher). Image credit: Dr Joseph Christopher.

I joined the Sanger Institute at the end of 2019, initially in Former Head of the Somatic Genomics programme, Dr Peter Campbell’s group. Around that time, Group Leader Dr Raheleh Rahbari had just received her Career Development Fellowship and was establishing her own team. My interests in germline predisposition – inherited genetic variants that increase disease risk – and rare genetic disorders aligned closely with her work, so I began working with her group and have continued to develop this work as part of that programme.

I went to medical school in Cambridge, and I did my PhD whilst I was there – it was called an MD-PhD. My PhD was looking at cancer predisposition in Lynch syndrome, which is a genetic condition that increases the risk of developing colorectal, endometrial and other cancers. We developed a new method for looking at how the cells in the colon of these mice behave compared to mice who don't have Lynch syndrome.

I graduated in 2018 and then spent a couple of years doing clinical rotations in the UK, working across different roles and teams to gain varied experience. Then I trained to be a paediatrician and was particularly interested in paediatric oncology, but soon realised it probably wasn't going to be for me. Clinical genetics allowed me to still work with cancer patients and their families whilst also developing my interest in early cancer and cancer predisposition, and particularly trying to find ways to detect cancer earlier and reduce risk in individuals with hereditary cancer risk.

Massively. Meeting with patients and their families every week gives you a real understanding of what they want and need. It keeps the science grounded in what matters to them, rather than what we, as scientists, assume is important. It’s a real privilege to build those relationships over time – some of these families we’ve known for years – and that trust shapes everything we do.

When research is driven by the questions patients actually want answered, they’re much more engaged. By working closely with them, we can also make studies more inclusive and accessible, so it’s easier for people to take part.

In most clinical trials, you might send out invitations and see around 20-30 per cent uptake. In rare disease research, that simply isn’t enough – you end up with very small cohorts. In a study we’re developing within Raheleh’s group, working with families at high cancer risk, we’ve seen participation rates of 80-90 per cent, effectively trebling recruitment. I believe that’s largely because of the relationships we’ve built, and because we take the time to clearly communicate what people are contributing to, so they can make informed decisions.

We have two conditions we're particularly interested. Li-Fraumeni syndrome is a rare, inherited genetic disorder that significantly increases the risk of developing multiple cancers, often at a young age. These individuals inherit a mutation in their TP53 tumour suppressor gene. It's rare, but we know it's underdiagnosed in the UK. The other condition we're interested in is PTEN Hamartoma Tumour Syndrome (PHTS). It is also a rare, inherited genetic condition this time caused by mutations in the PTEN tumour suppressor gene, leading to excessive cell growth and increased risk of benign and malignant tumours, particularly in the breast, thyroid, endometrium and kidney. A lot of these individuals will also develop neurodevelopmental conditions including autism and intellectual disability.

In work led within our group, we recently presented at a conference – and are hoping to submit a paper later this year – on our work in Li-Fraumeni syndrome, focussing on what we think of as these ‘bad’ cells. Normally, you have two functioning copies of a gene. In Li-Fraumeni syndrome, individuals are born with one faulty copy of TP53, and cancer is thought to develop when the second copy is lost.

Using cheek swabs and NanoSeq, we have observed early indications that a proportion of cells in cheek tissue may acquire changes affecting both copies of the gene in question. In some contexts, such as following chemotherapy, this proportion may be higher, although this requires further validation. Interestingly, these cells do not appear to cause any immediate or obvious problems, despite carrying changes that are strongly associated with cancer risk. We are actively working to better understand this observation.

At present, several hypotheses are being explored, but this remains an area of ongoing investigation. A key focus of future work will be to characterise these cells and their behaviour in more detail, which may in time help inform approaches to reducing cancer risk.

More broadly, these early findings raise questions about how different tissues respond to genetic changes. For example, while alterations in genes such as TP53 are well known to be associated with many cancers, their effects may vary depending on the tissue context. Understanding why some tissues appear more tolerant of such changes than others is an important area for further study.

The PTEN UK and Ireland Patient Group Patient Day 2025 Image credit: PTEN UK and Ireland Patient Group.

We’re currently setting up a post-mortem study. Individuals with rare cancer predisposition, such as Li-Fraumeni syndrome, can choose to donate their tissues after their death to support this research, which is an incredibly generous decision. We will aim to collect samples within 12 hours, which will allow us to preserve the tissue in a state that’s as informative as possible. This gives us a unique opportunity to study multiple tissues – from cheek cells to breast tissue and beyond – all from the same individual. By comparing these, we hope to gain insights into why some tissues appear more resilient to cancer, while others are more vulnerable.

The most rewarding part is discovery. I still remember seeing the cheek swab data for the first time – it was completely unexpected. You invest so much effort into collecting samples, working with families, and carrying out the technical work and analysis, so to uncover something entirely new is incredibly exciting. I also really value the collaborative side of science. Modern research is a team effort, and sharing those moments of discovery makes it even more meaningful.

The most challenging part is building momentum. Moving from a patient in the clinic to a meaningful scientific finding involves many steps, all of which need to align. At Sanger, we’re fortunate to have strong infrastructure in place, and setting up the initial study across Cambridge University Hospitals and Sanger relied on close collaboration, careful coordination, and the support of NHS colleagues working in a very busy clinical environment. Securing funding, engaging with patients, and ensuring the work is genuinely co-produced all take time and persistence. There were points where it felt quite isolating, and not everyone immediately saw the vision.

That said, once momentum builds, everything changes. We’re now in a position where recruitment is strong, sample collection is growing, and the network has expanded to six sites across the UK. With that foundation in place, we can really focus on collaborative discovery – and that’s when the work becomes most rewarding.

LFS UK 2025 event. Image credit: George Pantziarka TP53 Trust.

Don’t go alone. It’s tempting to try and move quickly on your own, but you can only get so far that way. Bringing people with you takes time – you have to share your vision, build trust and create a team – and that process can be difficult. At times, it can be frustrating, and you may feel like progress is slow. But in the long run, it’s worth it. A strong team and a supportive network allow you to go much further than you ever could alone. It may take longer and require more effort, but the impact is far greater.

I’m a father of two, so I really value spending time with my kids. It’s a complete contrast to work, which can be intense and demanding at times. They’re three and six, and they don’t care what I do or whether a project is going well or not – they just want me to be their dad. There’s something very grounding in that.

I also enjoy long-distance running. I used to be really into marathons – my wife and I have completed four of the six World Marathon Majors, with Boston and Tokyo still to go. Although I’ve heard they might be expanding the series now, which is slightly frustrating – we thought we were close to finishing! Running has become a kind of meditation for me. Once I find the right rhythm, it’s very therapeutic and gives me space to think.

I watched Hamnet last year and thought it was incredible. It really explores themes of parenthood and impermanence, and it stayed with me for a long time.

At the moment, I’m reading Thinking, Fast and Slow by Daniel Kahneman. He won the Nobel Prize in Economics for his work on decision-making, and he describes two modes of thinking: system one and system two. System one is fast and intuitive – almost automatic, like when you’re driving. System two is slower and more deliberate, requiring deeper thought. A lot of the research we do relies on that second mode, which makes the book particularly interesting to reflect on.