Crohn’s disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease (IBD) in developed nations such as Australia. It is common for a patient’s symptoms to first appear while they are in their 30s, although these diseases can affect children and older adults. IBD is a chronic illness and the symptoms, including diarrhoea, rectal bleeding, and abdominal pain, have a significant impact on quality of life.
The origin of IBD is not well understood, but the most favoured theory is that a genetically at-risk individual encounters a single or series of environmental triggers that lead to disease. Discovery of the first susceptibility gene for CD (called NOD2) and its proposed role in the body, support this hypothesis. We are currently investigating several other genes for links to IBD.
Both CD and UC are characterised by a series of relapses and remissions. There is limited understanding of the clinical, environmental and genetic factors that may influence how severe the disease is or how often it recurs. The IBD Research Group is analysing a broad range of factors in a large cohort of IBD patients.
Group Head: Dr Graham Radford-Smith
- Lisa Simms, Senior Laboratory Coordinator
- Katherine Hanigan, Research Assistant
Anderson CA, Boucher G, Lees CW, Franke A, D’Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagacé C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RS, Floyd JA, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lémann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panés J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature Genetics 2011 Mar:43:246-52.
Rossin EJ, Lage K, Raychaudhuri S, Xavier RJ, Tatar D, Benita Y; International Inflammatory Bowel Disease Genetics Constortium, Cotsapas C, Daly MJ. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genetics 2011 Jan 13;7(1):e1001273.
Eri RD, Adams RJ, Tran TV, Tong H, Das I, Roche DK, Oancea I, Png CW, Jeffery PL, Radford-Smith GL, Cook MC, Florin TH, McGuckin MA. An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity. Mucosal Immunology 2011 May;4(3):354-64. Epub 2010 Nov 24.
Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Cohen A, Colombel JF, Cottone M, Stronati L, Denson T, De Vos M, D’Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, Van Gossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot JP, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panés J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PC, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D’Amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, Parkes M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nature Genetics 2010 Dec;42(12):1118-25.
Lawrance IC, Radford-Smith GL, Bampton PA, Andrews JM, Tan PK, Croft A, Gearry RB, Florin TH. Serious infections in patients with inflammatory bowel disease receiving anti-tumor-necrosis-factor-alpha therapy: an Australian and New Zealand experience. Journal of Gastroenterology and Hepatology 2010 Nov;25(11):1732-8.
Simms LA, Doecke JD, Roberts RL, Fowler EV, Zhao ZZ, McGuckin MA, Huang N, Hayward NK, Webb PM, Whiteman DC, Cavanaugh JA, McCallum R, Florin THJ, Barclay ML, Gearry RB, Merriman TR, Montgomery GW, Radford-Smith GL. KCNN4 gene variant is associated with ileal Crohn’s Disease in the Australian and New Zealand population. The American Journal of Gastroenterology 2010 Oct;105(10):2209-17. Epub 2010 Apr 20.
Burger DC, Lawrance IC, Bampton PA, Prosser R, Croft A, Gilshenan K, Radford-Smith GL, Florin TH. Anti-tumour necrosis factor-alpha treatment for perianal Crohn’s disease in Australia. The Medical Journal of Australia 2010 Apr 5;192(7):375-7.
Chapman-Kiddell CA, Davies PS, Gillen L, Radford-Smith GL. Role of diet in the development of inflammatory bowel disease.Inflammatory Bowel Diseases 2010 Jan;16(1):137-51. Review.
L A Simms, J D Doecke and GL Radford-Smith. Alpha-defensin expression shows no association with NOD2 status in patients with ileal Crohn’s disease. Gut 2009 58(6):883-4. Authors’ reply.
Togashi K, Hewett DG, Radford-Smith GL, Francis L, Leggett BA, Appleyard MN. The use of indigocarmine spray increases the colonoscopic detection rate of adenomas. Journal of Gastroenterology 2009;44(8):826-33. Epub 2009 May 16.
Lee N, Radford-Smith GL, Forwood M, Wong J, Taaffe DR. Body composition and muscle strength as predictors of bone mineral density in Crohn’s disease. Journal of Bone and Mineral Metabolism 2009;27(4):456-63. Epub 2009 Mar 31.
Hume GE, Radford-Smith GL. ACE inhibitors and angiotensin II receptor antagonists in Crohn’s disease management. Expert Review of Gastroenterology & Hepatology 2008 Oct;2(5):645-51. Review.
Fowler EV, Doecke J, Simms LA, Zhao ZZ, Webb PM, Hayward NK, Whiteman DC, Florin TH, Montgomery GW, Cavanaugh JA, Radford-Smith GL. ATG16L1 T300A shows strong associations with disease subgroups in a large Australian IBD population: further support for significant disease heterogeneity. The American Journal of Gastroenterology 2008 Oct;103(10):2519-26. Epub 2008 Jul 30.
McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G. Intestinal barrier dysfunction in inflammatory bowel diseases.Inflammatory Bowel Diseases 2009 Jan;15(1):100-13. Review.
Simms LA, Doecke JD, Walsh MD, Huang N, Fowler EV, Radford-Smith GL. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn’s disease. Gut 2008 Jul;57(7):903-10. Epub 2008 Feb 27.
Hume GE, Fowler EV, Doecke J, Simms LA, Huang N, Palmieri O, Griffiths LR, Florin TH, Annese V, Radford-Smith GL. Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohn’s disease in an Australian population.Inflammatory Bowel Diseases. 2008 May;14(5):585-90.
Koloski NA, Brett L, Radford-Smith G. Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature.World Journal of Gastroenterology 2008 Jan 14;14(2):165-73. Review.
Houston AM, Michael-Robinson JM, Walsh MD, Cummings MC, Ryan AE, Lincoln D, Pandeya N, Jass JR, Radford-Smith GL, O’Connell J. The “Fas counterattack” is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability. Human Pathology 2008 Feb;39(2):243-50. Epub 2007 Oct 24.
Selby W, Pavli P, Crotty B, Florin T, Radford-Smith G, Gibson P, Mitchell B, Connell W, Read R, Merrett M, Ee H, Hetzel D; Antibiotics in Crohn’s Disease Study Group. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007 Jun;132(7):2313-9. Epub 2007 Mar 21.
Lee N, Fowler E, Mason S, Lincoln D, Taaffe DR, Radford-Smith G. Tumor necrosis factor-alpha haplotype is strongly associated with bone mineral density in patients with Crohn’s disease. Journal of Gastroenterology and Hepatology 2007 Jun;22(6):913-9.
Gibson PR, Weston AR, Shann A, Florin TH, Lawrance IC, Macrae FA, Radford-Smith G. Relationship between disease severity, quality of life and health-care resource use in a cross-section of Australian patients with Crohn’s disease. Journal of Gastroenterology and Hepatology 2007 Aug;22(8):1306-12. Epub 2007 Jun 7.
Reinisch W, Sandborn WJ, Bala M, Yan S, Feagan BG, Rutgeerts P, Radford-Smith G, Xu S, Eisenberg D, Olson A, Colombel JF. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis. Inflammatory Bowel Diseases 2007 Sep;13(9):1135-40.
Radford-Smith G, O’Rourke P. How useful are biomarkers for the prediction of short-term relapse in patients with Crohn’s disease? Nature Clinical Practice. Gastroenterology & Hepatology 2007 Feb;4(2):72-3.
Radford-Smith G, Pandeya N. Associations between NOD2/CARD15 genotype and phenotype in Crohn’s disease–Are we there yet? World Journal of Gastroenterology 2006 Nov 28;12(44):7097-103. Review.
Hume GE, Fowler EV, Lincoln D, Eri R, Templeton D, Florin TH, Cavanaugh JA, Radford-Smith GL. Angiotensinogen and transforming growth factor beta1: novel genes in the pathogenesis of Crohn’s disease. Journal of Medical Genetics 2006 Oct;43(10):e51.
Gibson PR, Fixa B, Pekárková B, Bátovský M, Radford-Smith G, Tibitanzl J, Gabalec L, Florin TH, Greinwald R. Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets with ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis. Alimentary Pharmacology & Therapeutics 2006 Apr 1;23(7):1017-26.
Florin THJ, Patterson E, Fowler E, Radford-Smith GL. Clinically active Crohn’s disease in the presence of a low C-reactive protein. Scandinavian Journal of Gastroenterology 2006;41:306-11.
Makins RJ, Radford-Smith GL. Appendicectomy for Ulcerative Colitis – a Therapeutic Option? In “Clinical dilemmas in inflammatory bowel disease”. Ed. Irving P, Rampton DS, Shanahan F. Blackwell Publishing. Ltd, c2006.
Feagan BG, Sandborn WJ, Lichtenstein G, Radford-Smith GL, et al. CDP-571, a humanized monoclonal antibody to TNF-a, for steroid-dependent Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Alimentary Pharmacology & Therapeutics 2006;23:617-28.
Michael-Robinson JM, Pandeya N, Walsh MD, Biemer-Huttmann A-E, Eri R, Buttenshaw RL, Lincoln D, Clouston AD, Jass JR, Radford-Smith GL. Characterisation of tumour infiltrating lymphocytes and apoptosis in colitis-associated neoplasia.Journal of Pathology 2006;208:381-7.
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