Professor Matthew Brown is one of the world’s leading experts in genomics, the study of the human genome (DNA), and boasts an incredible resume of scientific and medical discoveries and achievements.
He has contributed to the development of gene-mapping approaches in numerous diseases and genome-wide association study methodology that has led to the discovery of thousands of genetic variants, particularly in the areas of ankylosing spondylitis, rheumatoid arthritis, and osteoporosis.
He was elected as a Fellow of the Australia Academy of Science in 2011 and was awarded the Premier’s Fellowship for Science in 2013.
Currently in the role of Chief Scientific Officer for Genomics England and Professor of Medicine at King’s College London, Professor Brown gives credit to the PA Research Foundation for having the courage and foresight to see the value in funding a key piece of equipment he needed when he started researching in Brisbane in 2005.
“At the time I was coming back from the Wellcome Trust Centre for Human Genetics at the University of Oxford, and I was setting up a laboratory to do common disease genetic studies. At Oxford, I was part of a large consortium which developed the genome-wide association study method for identifying common disease chains and I needed support to be able to set up the equipment to be able to run these sorts of studies and follow-up studies in Brisbane,” Professor Brown said.
“The PA Foundation funds went towards a Corbett real-time thermal cycler, what that meant was that we could take genetic findings and work out whether they affected the expression of individual genes. It’s an important step from genome-wide association studies to work out whether the genetic variants that you identify as being associated with diseases operate to cause the disease by affecting the expression of particular genes.
“That piece of equipment got used for the next 15 years that I was in Brisbane, and it was really helpful in getting the lab set up so we could do a whole stack of different experiments downstream of genome-wide association studies.
“Out of that work we published something like 30 Nature/Nature Genetics papers in the 15 years that I was in Brisbane.
“The main thing I think was that it meant that we were able to set up and do research that was competitive with the rest of the world and that we're able to do really high impact research that not only got published in high impact journals but led to some major changes in management of patients and drug development programs around the world.”
Professor Brown, who still practices medicine today in the rheumatology field, became interested in genetics through his father, who himself was a medical specialist. He has combined his interests in a long and distinguished career as both a clinician and scientist.
“I was interested in rheumatology separately to my interest in genetics. I've been interested in genetics from an early age because of my dad's role as a pediatrician who specialized in managing kids with cystic fibrosis,” Professor Brown said.
“I'd seen the discovery of the cystic fibrosis gene and that was a fascinating time that brought a lot of hope to cystic fibrosis patients and ultimately has led to a treatment of cystic fibrosis.
“As a medical student, I saw lots of rheumatology patients and it was just a fascinating group of conditions in general, but what really stood out were the patients, who were living and coping with chronic diseases for which we had little treatment, which was very inspiring.
“Most common diseases are heritable. In contrast to rare genetic diseases, such as cystic fibrosis, where typically just one gene with a big effect is involved, common diseases like arthritis, vascular disease, diabetes, mental health disorders and so on, have thousands of genes involved, each with individually small effects.
“Identifying the genes involved in common diseases was therefore much harder than for single gene diseases. It wasn't until after I'd been researching for a decade by 2004-2005 that we had effective methods to identify genes for these common diseases.
“That's led to the discovery of now literally tens of thousands of genes for common diseases, and now most drug discovery programs around the world are informed by genetic discoveries from the new methods that were developed."
Professor Brown said he felt donors to the Foundation could feel proud of their support of the charity and its support of genomics research because the field has displayed the power to change outcomes for the better for hospital patients.
“In 2006 we published a paper shortly after I came back from Oxford, on a rare single gene disease called fibrodysplasia ossificans progressiva.
“It's a severe condition when kids are born with just slightly bent big toes and that's it. But then they get episodes of inflammation in soft tissues and muscles which can be induced by little bumps, vaccinations, even just viral infections.
“Where those would normally heal without scarring in an unaffected individual in these people with this condition, they get quite marked inflammation around the trauma and that turns into bone, which accumulates around the body and causes progressive disability. Affected people lose mobility and become progressively more dependent on others for support, typically being bed-bound by their 30s, and having a reduced life expectancy.
“Identifying the gene for that that led to a drug discovery program and clinical trials which we assisted in at the PA Hospital.
“A couple of weeks ago the US Food and Drug Administration licensed the first medication for this disease which we did the clinical trials for in Brisbane, and which halves the rate of progression of the disease.
“That's an example of basically how therapies are really advancing fast for a single gene disease. That's a field where over the next five to ten years we're going to see an absolute revolution in therapies.
“In common diseases these different approaches have led to new treatments. For example in ankylosing spondylitis, a common rheumatic disease, one of the first genes we discovered was a receptor for a secreted protein called a cytokine, named interleukin-23 and it leads to production of IL-17.
“We pointed out to a company that had a blocker for this cytokine that they should try it in ankylosing spondylitis, because of the genetic finding and they did. It is now one of the global established treatments for this disease and is a multi-billion dollar per annum pharmaceutical. That sort of repositioning is one thing that genetics does.
“The other thing it does is that it points out new things that you could target for therapies so that if a drug company targets something where there's a known genetic association, the likelihood that the drug is going to be effective and gets through clinical trials is two to three times the average."
As a clinician scientist himself, Professor Brown said the Foundation’s focus on enabling clinicians to undertake research will be of great benefit to hospital patients at the PA and across the world.
“Without clinician scientists, then the link between laboratory and clinical practice is difficult to establish and clinician scientists who work closely with laboratory researchers are remarkably valuable people because they have a great understanding of biology and of how the human body operates in health and in response to disease," he said.
While it's very uncommon for clinicians to get to the level of skill in basic lab sciences or analysis that pure scientists have, they can get to a high level of expertise to the point that they can be really useful partners for specialist scientists in bridging that gap between the pure research and clinical application. So, I think it's tremendously valuable for the process of medical research.
“As a clinician if you're seeing patients every day, then that's very valuable. But you can only benefit the number of people who you actually see. Whereas if you do medical research and bring about a major change in medical practice through your research, you can benefit an extremely large number of people around the world.”
“The PA Foundation funds went towards a Corbett real-time thermal cycler, what that meant was that we could take genetic findings and work out whether they affected the expression of individual genes.
It’s an important step from genome-wide association studies to work out whether the genetic variants that you identify as being associated with diseases operate to cause the disease by affecting the expression of particular genes."
- Professor Matt Brown.
