Time to meet our new chief scientist – Professor KJ Patel

Firstly, welcome to CRUK! You have had an incredibly varied research career – can you give us a quick whistle-stop tour?

Thank you! So, I am Kenyan British Asian and read medicine at the University of London in 1986, and subsequently trained as a gastroenterologist in London. I then undertook a PhD in molecular immunology at the MRC Laboratory of Molecular Biology (LMB) in Cambridge after which I combined completing my medical specialist training and research supported by an MRC Clinician Scientist fellowship.

This was an exciting period where, together with Ashok Venkitaraman, we discovered that BRCA2 functioned in DNA repair. I was offered a junior group leader position at the LMB to start my own lab and I started to work on how cells fix a particular type of crosslinked DNA damage. Crosslinks are caused by many chemotherapeutic agents – it’s what makes this form of DNA damage very toxic to cancer cells and unfortunately normal cells as well.

Over the many years my lab played a central role in identifying the repair factors that remove crosslinks and showing how they work. However, the most important question we asked was why we need to remove crosslinks in the first place. This can’t be because we need to protect ourselves against chemotherapy, and in fact all living organisms (even down to bacteria) have a repair system to remove crosslinks. This research led to the discovery that aldehydes are factors that crosslink our DNA. These aldehydes arise when we drink alcohol, so in a way our research explains how alcohol damages our DNA and through which it might promote cancer.

In 2012 I was elected to the Academy of Medical Sciences and became a member of EMBO and in 2015 to the Royal Society. In 2020 I was appointed as director of the MRC Weatherall Institute of Molecular Medicine at Oxford University and the MRC Molecular Haematology Unit.

What is your sense of the frontiers of cancer research right now? Are there any areas which you find particularly exciting?

We are in truly exciting times in the life sciences because of revolutionary and disruptive technologies that greatly improve the scale and scope with which we can understand basic and diseased biological processes. There are four that I’d like to pick out:

1. The ability to sequence the code of life at speed and scale (genomics)
2. The ability to alter the code of life in cells and organisms with accuracy, rapidity and ease (CRISPR technologies)
3. The ability to define the molecular architecture of proteins (the workhorses of biological processes) with speed and accuracy (cryo electron microscopy technology)
4. The increasing power of computation and AI to process information, identify patterns and provide accurate predictions about the behaviour of cells and shape of the molecules of life

So, what are the outstanding questions in cancer biology that we can use these technologies for? We know that altered genes drive cancers and that there is a pattern to which combinations should instruct a normal cell to become cancerous. This is clearly seen in normal cells when grown in a dish and where these alterations are made. However, we now know that in our bodies we harbour cells that are similarly mis instructed and should, in principle, be cancerous – but they are not. Why is this the case? What lights the fuse of a dormant pre-cancer cell?

The fact that those questions still need answers show us how important it is to not just study the cancer cell growing in isolation in a dish but, rather, to study its evolution and adaption in the organism. This could lead us to better understand how cancer evolves in its site of origin and becomes invasive. How does the host protect against this and why and when does this protection fail so that the cancer prevails? How might cancers learn to steal resources from the host to develop and spread? And how are cancers able to adapt so quickly to fight against host defences and the treatments thrown at them?

Then there is a multitude questions surrounding causality. We know that there are many external factors that can cause cancers in humans, but we also know that cancer is linked to ageing. So, how does the process of ageing promote the emergence of cancer? Is it simply that cells have time to accrue the genetic changes that can cause a cancer? Or could there be more generalisable reasons why the older host is more susceptible to the growth and invasion of a cancer?

Linked to the broader question of age and cancer is the unusual and unexplained observation that certain mammals, particularly large ones (whales and elephants for example) are much less cancer prone – known as Peto’s paradox.

How do you see your role as chief scientist for CRUK and what can the research community expect?

I see my main role as helping direct funding and support to the very best science in cancer research. I will continue to ensure that our institutes and funded laboratories provide the best research environment so that our investment has the best chance of delivering ground-breaking discoveries and inventions.

An important part of the role is also to engage with our scientists and listen to their concerns so that I can represent them when I inform and engage with our committees, leadership and board.

What role do you think curiosity-lead research plays in a goal-directed organisation such as CRUK?

Curiosity lead research is crucial, it is the essence of many of the ground-breaking discoveries and inventions that have made our funded research so impactful. We must understand fundamental biology and understand how this is subverted in cancer – in this way curiosity and goal-driven research goes hand in hand. That said, there are certain contexts when we need to be more directed in what we fund, particularly when a specific breakthrough leads to direct translation.

What aspects are you most looking forward to as you take on the chief scientist role?

CRUK supported my own research at a critical stage, it made a huge difference in this context. I would like to ensure that others benefit the way I did so that we can beat cancer.

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