Image credit: Onur Pinar / Wellcome Sanger Institute
Dr David Adams, Senior Group Leader at the Wellcome Sanger Institute, is a pioneer in cancer biology and uncovering skin cancer genetics. We explore his 20-year career at Sanger and the global impact of his research.
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Cancer presents one of the biggest global health challenges, with skin cancers among the most common groups diagnosed worldwide. In 2022, there were over 1.5 million new cases of skin cancer1. These cancers are categorised as either melanomas, which develop in skin cells called melanocytes, or non-melanomas, which affect other skin cell types. Melanocytes are cells that contain a pigment called melanin, which gives skin its colour and provides some protection from the sun’s ultraviolet (UV) radiation.
Melanoma is the fifth most common cancer in the UK2, and while treatments have progressed in recent years, it is still the deadliest form of skin cancer. Dave Adams leads a team at the Sanger Institute that study a range of cancer types, with a focus on melanoma. His work has created a foundational understanding of cancer genetics and the results hold promise for new treatments. Dave has recently stepped up as Interim Head of the Cancer, Ageing and Somatic Mutation research programme at the Sanger Institute.
A journey into skin cancer research
Dave grew up in a rural farming region in Australia, surrounded by animals. As a child, he became curious about the similarities and differences among the animals, which later inspired his fascination with genetics. He graduated from the University of Sydney with a PhD in medicine, focusing on cardiovascular disease and blood pressure regulation.
“The reason I work on skin cancers is because in Australia they became a major problem. I had personal experience with people suffering from melanoma. So, even during my PhD I was interested in skin cancers. As my career progressed, I met key people in the field, including Professors Tim Bishop and Julia Newton Bishop at Leeds University, who inspired me to focus on skin cancers.”
Dr Dave Adams,
Interim Head of Cancer, Ageing and Somatic Mutation Programme, Wellcome Sanger Institute
Dave joined the Sanger Institute in 2001 as a postdoc and his research investigated why particular genes contribute to disease. He went on to lead a research programme that sequenced the genomes of 17 strains of mice3, providing a huge catalogue of genetic variations linked to specific functions. These reference genomes have been used extensively in research across the globe.
In 2012, Dave became a senior group leader and focused on the link between heritable genetic mutations and cancer risk. Dave’s team carried out large-scale genetic sequencing studies to investigate cancer predisposition in families with an increased risk of melanoma. This research culminated in one of Dave’s most significant accomplishments – uncovering how the Protection of Telomeres 1 gene, POT14, impacts cancer. Telomeres are caps at the ends of chromosomes, made from repetitive DNA sequences and proteins. Telomeres play a role in cell senescence, which is which is when cells stop dividing and growing.
Certain POT1 gene variants result in excessively long telomeres, which Dave and his team showed for the first time can increase melanoma risk. This discovery challenged the previous view that only short telomeres were associated with cancer predisposition. One theory is that the long telomeres in these patients may disrupt normal cell senescence, so the cells continue to grow unchecked, leading to tumours.
Changes in the POT1 gene are now routinely screened for in families with a history of melanoma across the globe. Other researchers have since linked POT1 gene variants with chronic lymphocytic leukaemia (CLL), bowel cancer and a rare blood cancer called cutaneous T-cell lymphoma (CTCL).
Different ways to reveal the genetics of skin cancer
Alongside understanding the genomics of cancer, Dave’s team use other tools to explore cancer in a broader context. For instance, the immune system is known to play a key role in tumour development, so the team investigates the connections between the genome, immune system, and tumour environment. Dave’s team also uses machine learning to predict which genetic changes are likely to cause disease.
Dave is also a founding member of the Atlas of Variant Effects Alliance, which aims to create a comprehensive map of the effects of important genetic changes across the genome. Understanding these effects could eventually benefit biological research, drug discovery and medical practice. As part of this project, Dave’s team are developing high-throughput methods to identify genetic variations that may contribute to a person’s cancer risk, which could eventually lead to a useful tool for clinicians.
His team also leads Dermatlas, the world’s most comprehensive resource for exploring genetic changes found in human skin tumours. Dave’s team is sequencing and analysing the genomes of all rare skin tumours to understand how and why these tumours develop across different populations. This global collaboration requires a sufficiently large pool of data, given the rarity of these cancers, so the project includes samples from diverse populations, with notable success in Latin America.
Environment and behaviour impact skin cancer risk
Genetics plays a crucial role in the development of many skin cancers5, but for melanoma to occur, significant risk factors are exposure to UV radiation and individual behaviour. Specifically, there are different ways in which people experience sunburn, which carry varying levels of risk.
“If you're somebody who jets off to Portugal or Spain and gets really badly burnt – acutely burned from intense sun exposure on a short holiday – you're at much greater risk than someone who, for example, mows lawns for a living, where they're chronically exposed at a lower level.”
Dave’s research focuses on people with a strong family history of skin cancer, where multiple individuals across generations are affected. It is vital to identify which family members are most at risk to ensure they have regular dermatology visits, compared to those who are less at risk and surveillance is not essential. Regular screening in these cases can help detect and treat melanoma early, but also reduce the burden on healthcare systems such as the NHS, by focusing resources on those who need the screening.
For most people who do not have a strong family history of skin cancer, exposure to UV light is a critical risk factor in skin cancer formation, which is why it is so important to take preventive measures such as wearing sunscreen at SPF 50+, a hat, and sunglasses. In Australia, where Dave grew up, there is a longstanding appreciation of the risks of sun damage and extensive sun safety campaigns have been effective. However, he has noticed that in the UK, people seem to take unnecessary risks in the sun and are often more motivated to practice sun avoidance to reduce premature ageing of the skin, rather than reducing their skin cancer risk.
Global impact: collaborations and challenges
Dave explained that the two most beneficial things about working at the Sanger Institute are the ability to carry out genomic research at scale, and to contribute to large international collaborations such as the Dermatlas Project. He also regularly takes part in global training courses run by Wellcome Connecting Science.
“I was in Rio, Brazil recently helping to run a training course on single-cell sequencing. We’ve been holding this course for the past two years so far, and it is amazing to see what the Brazilian team have achieved with limited resources. These investigators complement Sanger very well because they have a similar ethos of openness and sharing in science, which is very powerful and impactful.”
Dave is co-head of the Sanger Excellence Fellowship for early career researchers from a Black heritage background. He is also involved in advocacy efforts for cancer genetic studies in low- and middle-income countries, especially in Latin America, which is funded by the MRC and the Royal Society.
Dave’s vision for skin cancer research
Dave believes that future skin cancer research will be driven by the need for personalised medicine. As scientists generate more genomes from populations around the world, research will continue to focus on what genetic changes do and how they influence our risk of diseases.
“Currently, people with potential predispositions to genetic disorders, including skin cancers, may be offered genetic testing. However, a significant challenge remains for genetic research – to interpret the genetic data and understand exactly which variants impact disease development.
While I can see a time when genomic sequencing could become routine in clinical practice to identify people’s genetic risk factors for skin cancer, far more research is needed into inherited genetic changes. There is a lot of complexity to contend with and other influences such as the environment.”
Dave explained that many biological fields are becoming more like physics – researchers are not divided into those that generate data and those that analyse it, most people are now equally comfortable in the lab and writing computer code. With the growing complexity of large-scale genomic data, skills in computational biology, machine learning, and large language models will become essential for generating biological insight.
“If I was a PhD student now and interested in cancer biology, I'd certainly be thinking carefully about being well-versed in machine learning and becoming extremely computationally competent. It's going to be a vital tool for interpreting large genetic data sets.
“On the other hand, we mustn’t underestimate the importance of technical laboratory skills. There have been huge breakthroughs resulting from skilled experimental biologists and people who can develop new methods and make them work at scale. Fundamentally, it is these skills that have driven the sequencing revolution on which the Sanger Institute has prospered for many years.”
During his career at the Sanger Institute, Dave and his team have helped elevate our understanding of the genetic factors behind skin cancer, especially melanoma. Moreover, this research is likely to support innovative new cancer treatments and personalised medicine. As researchers continue to uncover the complexities of cancer genetics and expand their use of advanced computational techniques, even greater progress can be achieved in cancer prevention, diagnosis, and treatment.
