‘Geeks at heart’ join forces to improve outcomes for people with melanoma

01 June 2021
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WEHI computational biologist Professor Tony Papenfuss teamed up with clinician-researcher Professor Mark Shackleton, Director of Oncology at Alfred Health and Monash University; to tackle melanoma research, improve outcomes and discover better treatments.


I can’t remember the exact point I first met Mark. He did his PhD at WEHI, though I am not sure if we ever crossed paths at that time.

When he returned from working overseas and approached me about collaborating, I knew we had a real opportunity to create impact.

Mark is a clinician with an interest in the clonal evolution of cancer. He comes at research with a strong understanding of how to test different ideas of clonal evolution in melanoma, whereas I come at it from a mathematical, statistical and data science direction. So our skill sets are complementary.

I liken our process to what jazz musicians call ‘riffing’: we dive deep into the data and this inspires new biological and algorithmic ideas that we bounce off one another. The fun parts are jointly coming up with questions we want to address, then letting the data guide the subsequent analyses.

“Working with Mark has given me a new appreciation of melanoma. He is incredibly interested in this field and in improving outcomes for people with this cancer.”
Professor Tony Papenfuss

Our recent publication looked at how melanoma genomes change as the disease progresses, with a particular emphasis on late-stage disease. A suite of theories emerged, which we are continuing to investigate. This paper took six years to complete, so it was a long-term project.

Now that we know the genomic changes occurring in melanoma as it progresses, we are investigating whether these changes differ between men and women. There are hints this is the case, but we need more data. We know there are sex-specific differences in melanoma, both in incidence and outcome, but there are a host of reasons that could be the case.

Mark and I regularly have fantastic conversations where we come up with all sorts of wonderful research ideas. It is an iterative process and often we come out of our discussions with more questions than answers, but that is what makes our relationship so important.

“We listen with enthusiasm to each other’s crazy ideas. Ours is a long-term, collaborative relationship and I think we will continue working together for many years to come.”
Professor Tony Papenfuss


I have been involved in treating and researching melanoma since the early 1990s.

I undertook a postdoc at the University of Michigan, US, and my interests snowballed from there. When I came back to Melbourne to start up a new lab, Tony was one of the first people I targeted to collaborate with.

I needed to work with someone with a background in the field of computational biology, as it was obvious this field of science was going to enable me to do experiments I would not otherwise be able to do.

We have our independent research endeavours, but if I have a research question that needs to be addressed by a molecular profiling experiment, Tony is my go-to collaborator. We feel that collectively we are better at answering some research questions than if we were to try and struggle on independently.

Apart from being a talented scientist, Tony is just a great guy and very easy to work with.

“Our recent publication showed that whole genome doubling was an almost universal event as melanoma progresses. This was a fundamentally important discovery.”
Professor Mark Shackleton

We need to understand why and how whole genome doubling happens, as it is clearly an important development during evolution of cancers within patients. Our data raises the possibility that targeting the mechanisms that permit whole genome doubling could be an effective and specific approach to cancer treatment.

“I have had some of the most interesting and invigorating scientific discussions of my career with Tony.”
Professor Mark Shackleton

We are both geeks at heart, who enjoy science and are fundamentally interested in making discoveries.

The ability for us to bring our different skills and experiences means we have been able to achieve more together than we would have individually. We have recently been discussing our next ideas and projects – we still have lots to do.

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