Professor Greg Hannon: “Core funding is a privilege and we should use it to tackle big problems in new ways”

Cancer Research UK

For the first stop on our virtual tour around the UK meeting the directors of our four leading institutes, we speak with Professor Greg Hannon who heads up the Cancer Research UK Cambridge Institute. He tells us about how his innovative work has benefited from philanthropy.

Professor Greg Hannon has four children, four goats, eight dogs, 18 chickens and a cat. He’s also Director of the Cancer Research UK Cambridge Institute and principal investigator of the mighty IMAXT, one of the teams funded by Cancer Grand Challenges – a global research funding platform founded by us and the US National Cancer Institute. IMAXT’s aim? To create virtual reality 3D maps of tumours to guide oncologists and people with cancer in treatment decisions. And on the rare occasions he finds some spare time, he moonlights as a potter, although a surging workload during the pandemic has meant that mugs and bowls have had to take a backseat in recent months.  

So it’s a wonder he had time to speak with us recently about his journey from plucky pre-med student in rural Pennsylvania – “I didn’t know my job now even existed then” – to institute director and IMAXT's principal investigator. But gladly, he did.

Shaking things up

Greg has led our Cancer Research UK Cambridge Institute for the past two years. Prior to his arrival in the UK around six years ago, he worked for 23 years at the prestigious Cold Spring Harbor Laboratory in New York. What prompted the move to our green and pleasant land? “It was a mixture of scientific and personal motivations,” he says. “I went to Cold Spring Harbor straight after completing my PhD. It was an amazing environment, which taught me to take chances and moulded the way I think about science. But ultimately, after more than two decades in one place, I wanted to shake things up. Also, my wife is English and she wanted to be nearer to her friends and family.”

After an unfortunate first experience of Cambridge involving a packed seminar room for a key-note speech, a laptop and a spilt can of coke, Greg was keen to give the city another chance as he had a good feeling about the place: “Cambridge had a great, smaller town feel to it, and yet I could still be in London quickly.”

But ultimately, it was the research potential that drew Greg to our Cambridge Institute. “The science here is fantastic and we have access to people working in other disciplines useful for cancer research, like maths, physics and chemistry,” he says. Coming on board as a senior group leader, Greg became institute director in 2018, a decision he describes as both hard – “I had to accept that I’d be stepping away from my own lab to some extent” – and easy – “I was very grateful to be given this huge opportunity to shape an amazing place like this”.

He has since built a research environment that has enabled some hugely exciting leaps forward in our understanding of cancer. Under his directorship, for example, group leaders Professors Richard Gilbertson and Carlos Caldas have established the Cancer Research UK Children’s Brain Tumour Centre of Excellence and the Personalised Breast Cancer Programme, respectively, and the institute leads one, and participates in two additional, Cancer Grand Challenges projects. More on this global initiative later.

Standing up to COVID-19

When the pandemic struck, Greg led the institute in its valiant COVID-19 testing efforts. “I’m extremely proud that our people – mainly PhD students – stood up and effectively ran testing for Addenbrooke’s Hospital for many months,” he says. “We ended up doing north of 10,000 tests.” As well as testing patients and NHS staff, the institute maintains a COVID-secure environment by testing its own staff every week, which has proved highly reassuring and allowed much of their vital research to continue.

Embracing cancer’s complexity

As well as running the institute as a whole, Greg also leads his own research group, which has pioneered a variety of cutting-edge genetic tools to address critical problems in cancer biology. These have helped the group investigate how the disease initiates and progresses, how tumours vary from person to person and how they evolve over time, known as tumour heterogeneity. “We’re interested in how the initiating cell of a tumour – its ancestor – diversifies,” he explains. “Not only does it acquire different mutations but also different characteristics and proficiencies, which affect how the cancer grows and, potentially, spreads. For about six years, we’ve been trying to understand what drives those differences, but almost more importantly, trying to mine these heterogeneous properties for new insight into the processes that drive the progression of the disease.”

Interestingly, his team didn’t set out to study any of the processes that they’re working on now. Instead, he says: “We let the biology tell us what we should focus on and we had to learn a lot of new things so we could chase those insights down.”

In a nutshell, what they learned was this:

  1. The availability of certain amino acids in a tumour’s environment can have an enormous impact on how the disease progresses, with one in particular, L-asparagine (so named because it was first isolated in juice from an asparagus), driving cancer’s spread. By manipulating the availability of L-asparagine, the team found they could reduce the potential for metastatic progression. They even found that they could do this by changing the diet of the test subject, and they now have plans to introduce dietary variation into clinical cancer care.
  2. When a tumour is starved of oxygen, it can re-programme its cells to mimic the properties of blood vessel cells. This ensures that the tumour cells can a) re-oxygenate and b) get into the blood stream, which allows them to spread around the body.

If that sounds over-simplified, that’s because it is. Cancer is, of course, notoriously complex. Not only is it more than 200 separate diseases, it expresses itself differently in each person and at each stage of its development. But far from shying away from this daunting intricacy, Greg encourages researchers to embrace it. His unofficial mission statement for the institute is: “Embracing complexity to achieve better outcomes for people with cancer”. He stresses that, in order to find the most tailored treatment for a person – the one that is going to have the best results – researchers need to be precise and targeted, and that involves going above and beyond traditional methods. “If researchers are willing to, for example, look at the whole population of cells within a tumour in tissue taken straight from a patient, rather than work with long-established Petri dish cell lines or tumour lab models, they will get a much more faithful representation of the situation.”

Treating funding as a privilege

Of course, none of this innovation-led work would be possible without core institutional funding provided by Cancer Research UK through our supporters and philanthropists. “That’s a huge benefit of working here,” says Greg. “Our work has benefited enormously from philanthropy. I’m always saying to the institute’s group leaders that core funding is a privilege and we should be using it to drive creativity and innovation, and tackle big problems in new ways.”

As well as continuing to embrace complexity to benefit people with cancer, Greg is also highly committed to fostering the institute’s next generation of science leaders. He is clearly passionate about building exceptional research talent and believes that the most important legacy of a great scientist isn’t the number of papers they’ve published in respected journals, but the number of excellent researchers who can name them as a mentor.

Greg’s “lab family”, as he calls it, spans not only institutes but continents – from California to Beijing. “I’m incredibly proud of them all – we still keep in touch,” he says, adding that he likes to teach his students to “take chances, think about big, hard questions and believe that anything is possible. Researchers must start with an openness to the possibility, and work backwards from there. A lot of the things we’ve done have been validated using that approach.”

Doing the impossible

One way he is helping to foster new talent is through his Cancer Grand Challenges research team, IMAXT, which stands for Imaging and Molecular Annotation of Xenografts and Tumours. In 2017, IMAXT secured £20m funding over five years, after impressing our panel of eminent scientists with their proposal to create 3D maps of tumours to better inform oncologists of their structure – vital information for treatment decisions. Since then, the team has made some truly remarkable progress, building completely new technologies and compressing methods that previously took years to complete into just a few hours, such as evolving an established 2D imaging technique called technology imaging mass cytometry to produce 3D reconstructions of tumour tissue. He explains: “Our project relied on techniques that weren’t yet in existence, so we built them. People told us it would be impossible, and yet here we are, using these new techniques effectively.”

The team comprises experts from a broad spectrum of research fields over and above biology – there are clinicians, mathematicians, chemists, physicists, computational biologists, even astronomers. It is a truly extraordinary meeting of minds and expertise. “There are special things that can happen when you give science an opportunity to pull together people who wouldn’t have met in another context,” he says.

Greg is certain that what he and the IMAXT team have achieved through Cancer Grand Challenges wouldn’t have happened without our supporters. “This kind of huge global effort couldn’t happen without Cancer Research UK having the bravery to invest on that scale,” he says. “And it wouldn’t have been able to happen without the support of visionary philanthropists.”

A new era of science

When we spoke, Joe Biden was still awaiting final confirmation of his election to the presidency. All eyes were on Greg’s home-state of Pennsylvania during the final days of the count. What are Greg’s expectations for the Biden-Harris administration’s approach to medical research?

“I’m very hopeful,” he says. “Biden has been quite active in the cancer space. I met him at a breast cancer research event when he was Vice President and he spoke genuinely and passionately about the power and promise of cancer science. I think he will promote the advancement of science and encourage the US to take its place on the global research stage.”

Through his visionary leadership and fearlessness in the face of seemingly insurmountable hurdles, and with the help of philanthropy, Greg is pushing the boundaries of what’s possible and making an enduring difference for people with cancer all over the world.

 

- Jo Lewin