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Doctor, doctor: meet Dr Mark Dawson

30 Jun, 2010
Dr Mark Dawson

Dr Mark Dawson

A medical degree is a big challenge, and so is postgraduate lab research. So what drives some people to undertake both and become clinician-scientists? Chrissie Giles spoke to Dr Mark Dawson about his motivation, the science of blood-based cancers and spelling bees.

You could say that the Wellcome Trust owes Mark Dawson. We’re in a car travelling to the Cambridge Institute for Medical Research as he recounts a painful childhood experience. Down to the final two in a primary school spelling bee in his native Australia, he was asked to spell ‘welcome’. Recalling some old Burroughs Wellcome & Co. items in his bathroom at home, he duly spelled out the double-L version. He lost.

Still, this early setback doesn’t seem to have damaged his career, or his relationship with the Trust. Recently awarded a Wellcome Trust Intermediate Clinical Fellowship, Dr Dawson also has the honour of being the first-ever recipient of a Wellcome-Beit Prize Fellowship, a sum of £25 000 provided in addition to his main award.

But what drives him and other doctors, dentists, vets and psychologists to develop a scientific career alongside their clinical work? How well does lab work sit alongside clinical responsibilities? What kind of person does it take to be a clinician scientist?

In the blood

Dr Dawson has always had a fascination with, and desire to improve the outcomes of, blood-based cancers, including leukaemia – cancer of the white blood cells. The field of leukaemia genetics was born in the 1960s, when researchers found a key genetic change in patients with chronic myeloid leukaemia. They showed that two chromosomes exchanged parts, creating a new gene and, in turn, a new protein. In the 1990s, scientists developed a drug, imatinib (Gleevec), that blocks the activity of this protein.

“When I started as a haematology trainee, most people with chronic myeloid leukaemia had to undergo a bone marrow transplant to get a lasting remission or cure,” says Dr Dawson. Some 15 per cent of patients died from the preparation for the transplant; those that survived the transplant often endured serious consequences.

“In my time, we’ve gone from this to giving people a drug they take a couple of times a day. It’s completely transformed their lives. I thought, that’s the kind of thing that I want to do: make a big difference by understanding how these things happen.”

Dr Dawson’s first taste of lab research came as a project on human cancer genetics using zebrafish, completed as part of his Bachelor of Medical Science degree. His involvement in clinical research continued after he qualified as a doctor, mainly in the areas of bone marrow transplantation and blood cancers.

This passion for being in the lab led him to do a PhD. Supported by a prestigious postgraduate scholarship awarded by the General Sir John Monash Foundation, he began his research in Cambridge in 2007.

Back to the bench

Dr Dawson’s PhD involved research on the myeloproliferative disorders, in which the bone marrow overproduces cells. Previous work by his supervisor, Prof. Anthony Green, found that almost every patient with polycythaemia vera (one of the myeloproliferative disorders) had a mutation in the JAK2 gene. This change results in the continuous activation of this finely regulated enzyme in people with the disease. It’s this abnormal continuous activity that drives the cancer.

“Knowing that there is a single mutation present in nearly all patients with disease gave us an incredible opportunity to try and understand the disease better,” says Dr Dawson.

Researchers thought that JAK2 acts as a mediator primarily in the cell’s cytoplasm, where it conveys messages from outside the cell to other proteins within the cytoplasm, which then enter the nucleus, ultimately affecting how genes are transcribed (turned into RNA). In his PhD work, Dr Dawson and colleagues showed that JAK2 is also present in the nucleus of the cell. What’s more, it can add a chemical group to histones – the protein scaffolds that support DNA – changing how accessible the DNA is. This, in turn, can alter the transcription of some genes. They showed for the first time that JAK2 can, by itself, directly influence what genes are expressed within a cell.

“We don’t know the full implications of this yet,” says Dr Dawson, “but it does give an avenue of research that was previously unknown.”

Chromatin biology – the field concerned with chromatin, the complex of DNA and its histone protein scaffolds – is burgeoning. “I knew nothing about the field three years ago, but I’ve been seduced by it,” he says. “Understanding how the cell is able to regulate access to the DNA is fascinating.” With his Intermediate Clinical Fellowship, Dr Dawson will study the role of chromatin changes in an aggressive condition called acute myeloid leukaemia. In this, and many other leukaemias, chromosomes break apart and rejoin differently. This can produce fusion genes, which, in some cases, drive the development of cancer. But how? Some fusion genes have special properties that may be involved. “One that I’m studying has the ability to reinstate self-renewal in cells that have lost the ability, effectively making them leukaemia stem cells,” he says.

As many fusion genes are known to modify chromatin (the DNA and histone bundles), Dr Dawson is looking to understand how changes in chromatin could lead to leukaemia stem cells. The next step will then be to understand the differences between leukaemia stem cells and normal blood stem cells (from which blood cells are made), to give researchers a way to destroy the cancer stem cells but spare the normal ones.

Getting clinical

Even with all this bench work, Dr Dawson will still see patients – as an honorary haematology consultant at Addenbrooke’s Hospital, he’ll spend around 10 per cent of his time on clinical duties. But with a career that combines clinical responsibilities with cutting-edge research, does he see himself choosing one over the other?

“As a clinician you’re working with people all the time. You’re let in very personally into their lives, and you can have a profound effect on them. I very much enjoy that,” he says. “Scientific research gives you perspective into how vast the task is, and how incremental the gains are, despite years of research. But these gains are very important.

“It seems to me that medicine and science marry very well. They extract from me two very different sides of my personality, but I can’t see myself losing either.”

Mark Dawson on…

…why he chose the UK
“In the UK, it’s well appreciated that clinician-scientists bring a different perspective than purely clinical or scientific researchers, and provide a bridge from bench to bedside. The opportunity that the Wellcome Trust has given me is not one I’d get at home.”

…what doing medicine brings to his scientific research
“As a clinician, the type of question I want to answer is based primarily on what is lacking clinically, which – for many blood-based cancers – is proper, targeted therapies. The only way to get these is by understanding the biology of the disease better.”

…what doing science brings to his clinical practice
“One of things we’re blessed with as clinicians is instant gratification – you make someone feel a bit better and they say thank you. That’s very rewarding, and is not something you get in science. Science brings a perspective of how vast the task is.”

…the one big question in leukaemia research
“How do we target leukaemia stem cells? If you think of leukaemia as a growing tree, the leukaemia stem cells are the root. Chemotherapy is like pruning the tree, but we don’t actually end up killing it, because we’re not targeting the roots.”

Need clinical funding?

The Trust offers support for clinicians – people qualified in medicine, dentistry, veterinary science or clinical psychology – at each stage of their career. Early-career schemes support graduates who have little or no research training, but who wish to develop a long-term career in academic medicine. Intermediate-career support includes Fellowships for MB/PhD Graduates and Intermediate Clinical Fellowships. Senior-career support includes research fellowships at the senior and principal levels. Visit our funding pages

Reference

Dawson MA et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 2009;461(7265):819-22.

Mark Dawson will complete his Fellowship in two institutes: Dr Brian Huntly’s lab at the Cambridge Institute for Medical Research, and Prof. Tony Kouzarides’s lab at the Wellcome Trust and Cancer Research UK Gurdon Institute, Cambridge.

Image credit: The Wellcome Trust
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