Professor Matt Brown
|Professor Matt Brown|
Choosing the latter, Brown moved to the Wellcome Trust Centre for Human Genetics at the University of Oxford in the UK, where he pursued an MD in the genetics of Ankylosing Spondylitis (AS), with Professor Paul Wordsworth, a renowned British rheumatologist. AS is a form of arthritis that involves chronic inflammation, particularly of the spinal and pelvic joints. The inflammation triggers uncontrolled bone growth, effectively fusing the spine and/or pelvis and causing significant pain and disability.
“I had always been fascinated by AS, a condition for which there were really no treatments at the time, and which had an obvious massive genetic component,” says Brown.
Brown continued his work at Oxford, building a large research group focused on the genetics of common bone and joint diseases. He was appointed Reader then Professor of Musculoskeletal Sciences, and then became a Fellow of the University. During that time, he collaborated extensively on osteoporosis genetics research with Professor John Eisman at the Garvan Institute in Sydney, a mentor who has had an invaluable impact on Brown’s career.
Brown returned to Australia in 2005 to become Professor of Immunogenetics at The University of Queensland Diamantina Institute (UQDI) where he established research programs in the genetics of common diseases, including AS, osteoporosis, rheumatoid arthritis, obesity, cancer and multiple sclerosis. He also became one of the founding investigators of the Wellcome Trust Case-Control Consortium (WTCCC), which developed the genomewide association study (GWAS), a new method for identifying genes in common human diseases that has had a profound influence on genetics.
“Genomewide association studies have identified over 2000 genes for common human diseases and have had a massive impact in virtually all areas of human biomedical research,” Brown explains. With regard to AS, they have identified 13 of the 14 genes known to be involved in the disease. He adds that this has had a significant international effect on AS research and has led to successful trials of new therapeutics.
“I am determined in my research career to develop treatments that end up in clinical practice, so my group has a large arm researching mechanisms by which genetic variants cause disease, and treatments based on that understanding.”
Brown and his colleagues also run a specialist service for AS patients at the adjacent Princess Alexandra Hospital. This allows them to provide excellent clinical service and, in turn, this direct access means they are one of very few groups worldwide able to do functional research directly in AS patients.
Brown believes the main challenge ahead is the need to better understand the biology underlying the genetic associations they have identified, but he is confident this challenge will be met.
“I feel very lucky to have been involved in genetics research at a time when it has absolutely boomed, and every day really fascinating insights about the basic causes of human diseases are being reported. The excitement that this brings is intoxicating, and is one of the major things that drives me to turn up to work each day.”
The opportunity to help outstanding young scientists develop, and being pushed himself to keep up with them is another major incentive, he adds. "Watching them fly is one of the great rewards for group leaders such as myself.”
Professor Brown's group researches genetics of common diseases, particularly musculoskeletal diseases. They are the central genetics research centre for the Australo-Anglo-American Spondyloarthritis Consortium, the main international AS genetics group. In addition, the group is performing genomewide association studies in multiple sclerosis, osteoporosis, cervical cancer, rheumatoid arthritis, schizophrenia, asthma and several other diseases. Professor Brown is a Principal Investigator of the Wellcome Trust Case-Control Consortium which did much of the development work and proof of principle studies for genomewide association studies, and is now involved in developing the approaches required for downstream genetics research (resequencing, fine-mapping, copy number variation studies). Professor Brown’s group also collaborates with researchers at the MRC Mammalian Research Facility Harwell, England, in ENU-mutagenesis approaches to develop new mouse strains with bone and joint disorders. Other major collaborations include with Professor Jon Tobias and Dr Celia Gregson (Bristol, UK) on genetics of high bone mass, Professor Huji Xu (Shanghai, China) on genetics of rheumatoid arthritis and ankylosing spondylitis in Han Chinese, and Professor Jamie Craig and Dr Kathryn Burdon (Adelaide, Aus) on genetics of ocular disorders.
Genetics of Common Bone and Joint Diseases
· Ankylosing spondylitis
· Rheumatoid arthritis
10 Recent Publications
- ‘Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.’ Reveille JD, Sims AM, Danoy P, Evans DM, Leo P, Pointon JJ, Jin R, Zhou X, Bradbury LA, Appleton LH, Davis JC, Diekman L, Doan T, Dowling A, Duan R, Duncan EL, Farrar C, Hadler J, Harvey D, Karaderi T, Mogg R, Pomeroy E, Pryce K, Taylor J, Savage L, Deloukas P, Kumanduri V, Peltonen L, Ring SM, Whittaker P, Glazov E, Thomas GP, Maksymowych WP, Inman RD, Ward MM, Stone MA, Weisman MH, Wordsworth BP, Brown MA. Nat Genet;42:123-7, 2010.
- ‘Genomewide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20.’ The Australian and New Zealand Multiple Sclerosis Genetics Consortium (Brown MA, principal investigator). Nat Genet. 41(7), 824-8, 2009.
- ‘Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants’. Wellcome Trust Case-Control Consortium (Brown MA, principal investigator), Australo-Anglo-American Spondyloarthritis Consortium (Brown MA, principal investigator), Nat Genet, Nat Genet, 39, 1329-1337, 2007.
- ‘Genomewide association study of 14,000 cases in seven common diseases and 3,000 shared controls’. Wellcome Trust Case-Control Consortium (Brown MA, principal investigator), Nature. 447, 661-84, 2007.
- ‘A recurrent mutation in the BMP type 1 receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva’. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, The FOP International Research Consortium, Brown MA, Kaplan FS. Nature Genet, 38 (5), 525-527, 2006.
- ‘ERAP1 but not IL23R is associated with ankylosing spondylitis in a Han Chinese population’. Davidson SI, Wu X, Wei M, Danoy P, Duncan EL, Cai Q, Sun L, Wang N, Yu Q, Xu A, Fu Y, Brown MA*, Xu H*. Arthritis Rheum, 60:3263-3268, 2009. *equal senior author.
- ‘Genetic Analyses in a Sample of Individuals With High or Low Bone Density Demonstrates Association With Multiple Wnt Pathway Genes.’ Sims AM, Shephard N, Carter K, Doan T, Dowling A, Duncan EL, Eisman J, Jones G, Nicholson G, Prince RL, Seeman E, Thomas G, Wass JA. and Brown MA. J Bone Miner Res, 23(4), 499-506, 2008.
- ‘Prospective meta-analysis of IL-1 gene complex polymorphisms confirms associations with ankylosing spondylitis.’ Sims AM, Timms AE, Bruges-Armas J, Chou CT, Doan T, Dowling A, Fialho RN, Gergely P, Gladman DD, Inman R, Kauppi M, Kaarela K, Laiho K, Maksymowych W, Rahman P, Reveille JD, Tuomilehto J, Wordsworth BP, Xu H, Brown MA. Ann Rheum Dis, 67(9), 1305-9, 2008.
- ‘Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.’ Timpson NJ, Tobias JH, Richards JB, Soranzo N, Duncan EL, Sims AM, Whittaker P, Kumanduri V, Zhai G, Glaser B, Eisman J, Jones G, Nicholson G, Prince R, Seeman E, Spector T, Brown MA, Peltonen L, Smith GD, Deloukas P, Evans DM. Hum Mol Genet. 18(8):1510-7, 2009.
- ‘Genetics and genomics of ankylosing spondylitis’. Thomas GP, Brown MA. Immunological Reviews, 233, 162-180, 2010.