An inspirational mentor and cell signalling pioneer: Chris Marshall

​Professor Chris Marshall, who died in August 2015 at the age of 66 from the disease he spent his life studying, was one of cancer biology’s most eminent scientists. 

Chris was not only a brilliant scientist but an outstanding scientific citizen. He believed strongly that CRUK, the funder of the majority of his work, had an obligation to its supporters to do the best science for the greatest patient benefit. His contributions to the strategic and scientific decision making of the organisation were invaluable, and his blend of rigour and informality will be sorely missed by CRUK staff.

Chris received a succession of major honours and awards throughout his career. He was elected as a Fellow of the Royal Society and the European Academy of Cancer Sciences, he was a founding member of the Academy of Medical Sciences, and he was a member of the European Molecular Biology Organisation. He was awarded the 1999 Novartis Medal of the Biochemical Society, the 2008 Buchanan Medal of the Royal Society and in 2015 the Biochemical Society Centenary Award. Chris had a long association with us and in 2011 was awarded the CRUK Lifetime Achievement in Cancer Research Prize.

At The Institute of Cancer Research, where he spent the bulk of his career, Chris was a generous and surprisingly soft-hearted colleague, and an excellent mentor with an eye for highly talented youngsters. Notable Marshall lab alumni include: Professor Karen Vousden, CRUK Chief Scientist; Dr Erik Sahai, Group Leader at the Francis Crick Institute; and Professor Richard Marais, Director of the CRUK Manchester Institute.

Chris Marshall’s Research

Chris established an international reputation for his research into tumour cell signalling, and leaves a lasting legacy of pioneering discoveries.

After discovering a major oncogene, NRAS, early on in his career, Chris went on to show, with his trademark scientific rigour, exactly how Ras proteins transmit signals from the outside of the cell, and how this signalling pathway becomes deregulated in cancer. He and his colleagues started by demonstrating that to signal effectively, Ras proteins must become associated with the cell membrane. Then, in a series of seminal papers, they showed that membrane-bound Ras proteins stimulate normal growth by switching on a signalling cascade called the MAP kinase pathway, and that mutant Ras proteins cause cancer by constitutively activating this pathway.

Chris was also one of the major driving forces in subsequent research to dissect the MAP kinase cascade, which turns out to be a vital universal signalling pathway. The details are highly complex, but in essence, Ras activates members of the Raf family, which then fire up a protein called MEK, which in turn switches on MAP kinase itself.

Chris’s work helped transform our understanding of how all cells, not just those in tumours, communicate – taking us from a model where proteins talk to each other in regimented lines to one of intricate signalling webs, with multiple layers of feedback loops and crosstalk. Teasing out the roles of Raf and MEK in malignant transformation has also been critical in advancing cancer therapeutics, inspiring the development of two new cancer drugs that are currently in widespread clinical use, benefiting patients worldwide.

 

Personal reflections from friends and colleagues

I first met Chris on a rainy August day in 1981 – I was just coming to the end of my PhD and had answered an advert in Nature for a postdoc in his lab. I have no idea why he hired me. I knew nothing about cell biology, nothing about cancer, nothing about anything really. He sat me in a chair where my legs didn’t touch the ground and talked at me with such excitement and enthusiasm about what he wanted to do I was smitten. I started in the lab a month later and it was like walking from a sepia tint world into bright Technicolor.

Chris was so supportive of the many of us who were lucky enough to pass through his lab. His warmth and generosity of spirit enveloped us and kept us going. For myself, I wanted nothing more than to please him and make him proud of me. We wrote our first paper and sent it to Nature – and one morning a few weeks later I noticed Chris behaving very oddly. It transpired the paper had been rejected and Chris didn’t want to tell me and upset me. What he didn’t realise was the only reason I was upset was because I thought I’d let him down.

There are so many memories; Chris perplexed by a result, Chris dancing when an experiment worked, Chris concentrating so hard when giving a talk that he forgets to open his eyes, Chris lighting up at a clever scientific insight or a nice bike, his crazy walk, Chris melting as he showed me photo after photo of his beloved grandchildren.

Chris was an inspiration and a role model. He was such an important person as a scientist – but even more so as the man who helped and supported so many of us. We will miss him immeasurably, but what a joy to have been able to share part of the journey with him.

Karen Vousden, CRUK Chief Scientist
 

“I had read all of Chris’s work before meeting him but even so, when I actually started working for him it was a revelation. He had such an influence on me and I wanted to be the same kind of scientist. He taught me how to be thorough, meticulous and how to get excited about data. I will deeply miss talking science with him as there was nothing more challenging than a good scientific discussion with Chris.”

Victoria Sanz-Moreno, CRUK Career Development Fellow, King’s College London
 

“Chris was a great mentor, friend and colleague. Importantly, he mentored while treating you as an equal; there was never any ‘preaching’, just informal suggestions and advice, mingled in the conversation. As a friend, I particularly enjoyed hearing about his bike exploits, even though I have never used a bike except out of necessity, his enthusiasm was captivating.”

Anne Ridley, Professor of Cell Biology, King’s College London
 

“Our work was heavily influenced by having Chris close by in London, providing advice, reagents, ideas and criticism. The nice thing about talking science with Chris was his robust response to ideas and results. And he was fun to drink with! It’s not the same without him.”

Richard Treisman, Scientific Director, Francis Crick Institute
 

“Shortly after I became Director of The Institute of Cancer Research in 1980, I met Chris at a conference in the US. I had admired his shrewd mind for some time, so I asked him there and then if he would consider a job at the ICR. I never regretted my impulse. Chris exceeded my already high expectations and soon became a major force in cell and molecular biology, as well as a good friend.”

Robin Weiss, Professor of Viral Oncology, UCL
 

“Chris was a truly brilliant and inspirational scientist. He had a long association with CRUK and its founding charities, and played a key role in helping to shape our Research Strategy and its implementation. Most recently he helped establish our Science Committee. He was a fantastic and tireless Chair of the committee, reading every grant application in detail but also bringing his own dry humour to ensure the committee did its job with great diligence.”

Iain Foulkes, Executive Director, Strategy and Research Funding
 

This story is part of Pioneering Research: our annual research publication for 2015/16.

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