Anne Griffiths , MD, FRCP(C)
The Hospital for Sick Children
Gastroenterology, Hepatology and Nutrition
Genetics & Genome Biology
Research Ethics Board
University of Toronto
SickKids Research Institute
Northbridge Chair in Inflammatory Bowel Disease
The Hospital for Sick Children
Anne M. Griffiths is a University of Toronto medical graduate, who trained in Paediatrics and Paediatric Gastroenterology at The Hospital for Sick Children, and in Clinical Epidemiology at the University of Toronto. She is currently Head of the Division of GI/Hepatology/ Nutrition in the Department of Paediatrics and co-director of its paediatric Inflammatory Bowel Disease (IBD) program, which integrates clinical care and research. Under her leadership the IBD program has played an important role in IBD genetic research since 1996, when efforts to understand the basis of genetic susceptibility first began.
She has been a co-investigator in the North American and International Paediatric and Adult IBD Genetics Consortia, which have been very successful in the use of first linkage and subsequently genome-wide association studies to identify genes influencing the development of ulcerative colitis and Crohn’s disease. She is Deputy Chair of the Executive Committee of the Crohn’s and Colitis Foundation of Canada Gene-environment-microbe study, which prospectively recruits healthy siblings and offspring of Crohn’s disease patients, in an effort to identify microbial and other environmental triggers of disease in genetically at-risk hosts.
She has contributed significantly to clinical trial design and outcome assessment in paediatric IBD, spearheading the development of a disease-specific measure of health-related quality of life (IMPACT questionnaire), and of the Paediatric Ulcerative Colitis Activity Index (PUCAI).
- Inflammatory Bowel Disease
- Gene Discovery
- Genotype/phenotype correlations in paediatric IBD Genetic basis of very early onset IBD Biologic therapies in IBD Use of imaging and biomarkers to assess evolution of IBD under treatment
Genetic predisposition appears particularly important in the pathogenesis of paediatric-onset inflammatory bowel disease. Dr. Griffiths and her colleagues are collecting blood for DNA isolation from families who have multiple affected members. From their database of 900 families, 50 affected sibling pairs have been identified. These pairs are a valuable resource for linkage analysis that uses genome scanning with microsatellite markers to identify the chromosomal sites of predisposing genes and for future studies of candidate genes.
Their second focus is on the evaluation of therapies. Dr. Griffiths and her colleagues are currently conducting a trial of two types of enteral nutrition in patients with active Crohn's disease. They will be studying controlled ileal-release budesonide, a new corticosteroid targeted at the intestine that has a much less systemic effect.
Waterman M, Xu W, Stempak JM, Milgrom R, Bernstein CN, Griffiths AM, Greenberg GR, Steinhart AH, Silverberg MS. Distinct and overlapping genetic loci in Crohn’s disease and ulcerative colitis: correlations with pathogenesis. Inflamm Bowel Dis epub Dec 10, 2010.
Andre Franke, Dermot P B McGovern, Jeffrey C Barrett, Kai Wang, Graham L Radford-Smith, Tariq Ahmad, Charlie W Lees, Tobias Balschun, James Lee, Rebecca Roberts, Carl A Anderson, Joshua C Bis, Suzanne Bumpstead, David Ellinghaus, Eleonora M Festen, Michel Georges, Todd Green, Talin Haritunians, Luke Jostins, Anna Latiano, Christopher G Mathew, Grant W Montgomery, Natalie J Prescott, Soumya Raychaudhuri, Jerome I Rotter, Philip Schumm, Yashoda Sharma, Lisa A Simms, Kent D Taylor, David Whiteman, Cisca Wijmenga, Robert N Baldassano, Murray Barclay, Theodore M Bayless, Stephan Brand, Carsten Büning, Albert Cohen, Jean-Frederick Colombel, Mario Cottone, Laura Stronati, Ted Denson, Martine De Vos, Renata D’Inca, Marla Dubinsky, Cathryn Edwards, Tim Florin, Denis Franchimont, Richard Gearry, Jürgen Glas, Andre Van Gossum, Stephen L Guthery, Jonas Halfvarson, Hein W Verspaget, Jean-Pierre Hugot, Amir Karban, Debby Laukens, Ian Lawrance, Marc Lemann, Arie Levine, Cecile Libioulle, Edouard Louis, Craig Mowat, William Newman, Julián Panés, Anne Phillips, Deborah D Proctor, Miguel Regueiro, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Frank Seibold, A Hillary Steinhart, Pieter C F Stokkers, Leif Torkvist, Gerd Kullak-Ublick, David Wilson, Thomas Walters, Stephan R Targan, Steven R Brant, John D Rioux, Mauro D’Amato, Rinse K Weersma, Subra Kugathasan, Anne M Griffiths, John C Mansfield, Severine Vermeire, Richard H Duerr, Mark S Silverberg, Jack Satsangi, Stefan Schreiber, Judy H Cho, Vito Annese, Hakon Hakonarsen, Mark Daly, Miles Parkes. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Published Nature Genetics on-line 21 November, 2010.
Levine A, Griffiths AM, Markowitz J, Wilson D, Turner D, Russell R, Fell J, Ruemmele F, Walters T, Sherlock M, Dubinsky M, and Hyams JS. Pediatric Modification of the Montreal Classification for Inflammatory Bowel Disease - the Paris Classification. Infl Bowel Dis epub November 2010.
Kabakchiev B, Turner D, Hyams J, Mack D, Leleiko N, Crandall W, Markowitz J, Otley AR, Xu W, Hu P, Griffiths AM, Silverberg MS. Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis. PLoS One 2010; Sep 30: 5 (9). Pii: e13085.
Wang K, Baldassano R, Zhang H, Qu HQ, Imielinksi M, Kuathasan S, Annese V, Dubinsky M, Rotter JI, Russell RK, Bradfield JP, Sleiman PM, Glessner JT, Walters T, Hou C, Kim C, Frackelton EC, Garris M, Doran J, Romano C, Catassi C, Van Limbergen K, Gethery SL, Denson L, Piccoli D, Silverberg MS, Stanley CA, Monos DC, Griffiths A, Grant SF, Satsangi J, Polychronakos C, Hakonarson H. Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects. Human Molecular Genetics 2010; 10:2059-67.
Turner D, Mack D, Leleiko N, Walters TD, Uusoue K, Leach ST, Day AS, Crandall W, Silverberg M, Markowitz J, Otley AR, Keljo K, Mamula P, Hyams J, Griffiths AM. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 2010: 138: pp 2282-2291.
Turner D, Leach ST, Mack D, Uusoue K, McLernon R, Hyams J , Leleiko N, Walters TD, Crandall W, Markowitz J, Otley AR, Griffiths AM, Day AS Fecal calprotectin, lactoferrin, M2-pyruvate kinase, and S100A12 in severe ulcerative colitis: a prospective multicenter comparison of predicting outcomes and monitoring response. Gut, 2010; 59: 1207-1212.
Muise AM, Walters TD, Glowacka WK, Griffiths AM, Ngan BY, Lan H, Xu W, Silverberg MS, Rotin D. Polymorphisms in E-cadherin (CDH-1) result in a mis-localised cytoplasmic protein that is associated with Crohn’s disease. Gut, 2009; 58: 1121-7.
*Imielinski M, *Baldassano R, *Griffiths AM, *Russell RK, *Annese V, *Dubinski M, *Kugathasan S, Bradfield J, Walters T, Sleiman P, Kim C, Glessner J, Saeed S, Frackelton E, Chiavacci R, Grundmeier R, Stempak J, Taylor K, Stephens M, Levine A, Piccoli D, Denson L, Van Limbergen J, Cucchiara S, Guthery S, Wilson D, Grant SFA, Daly M, Silverberg M, Sastsangi J, Hakonarson H. Common variants at 16p11 implicate IL-27 in childhood-onset inflammatory bowel disease. Nature Genetics 41: 1335-1340; 2009 * equal contribution
Benchimol E, Guttman A, Griffiths A, Rabeneck L, Mack D, Brill H, Howard J, Guan J, To T. Increasing incidence of paediatric IBD in Ontario, Canada: evidence from administrative health data. Gut 2009 58;1490-1497.
Griffiths AM, Nicholas D, Smith C, Munk M, Stephens D, Durno C, Sherman PM. Development of a quality-of-life index for pediatric inflammatory bowel disease: dealing with differences related to age and IBD type. Journal of Pediatric Gastroenterology and Nutrition, 28: S46-S52, 1999.
Durno CA, Ehrlich R, Taylor R, Buncic JR, Hughes P, Griffiths AM. Keeping an eye on Crohn's disease: orbital myositis as the presenting symptom. Canadian Journal of Gastroenterology, 11: 497-500, 1997.
Griffiths AM, Sherman PM. Colonoscopic surveillance for cancer in ulcerative colitis: a critical review. Journal of Pediatric Gastroenterology and Nutrition, 24: 202-210, 1997.
Azcue M, Rashid M, Griffiths A, Pencharz PB. Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone. Gut, 41: 203-208, 1997.
Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, Griffiths A. Supplementary enteral nutrition maintains remission in paediatric Crohn's disease. Gut, 38: 543-548, 1996.
Khoshoo V, Reifen R, Neuman MG, Griffiths A, Pencharz PB. Effect of low- and high-fat, peptide-based diets on body composition and disease activity in adolescents with active Crohn's disease. Journal of Parenteral and Enteral Nutrition, 20: 401-405, 1996.
Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease. Gastroenterology, 108: 1056-1067, 1995.
Eisenstat DD, Griffiths AM, Cutz E, Petric M, Drumm B. Acute cytomegalovirus infection in a child with Menetrier's disease. Gastroenterology, 109: 592-595, 1995.
Wilschanski M, Chait P, Wade JA, Davis L, Corey M, St. Louis P, Griffiths AM et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology, 22: 1415-1422, 1995.
Kim JH, Tagari P, Griffiths AM, Ford-Hutchinson A, Smith C, Sherman PM. Levels of peptidoleukotriene E4 are elevated in active Crohn's disease. Journal of Pediatric Gastroenterology and Nutrition, 20: 403-407, 1995.
Sylvester FA, Griffiths AM. Endothelins and the color of mice: unraveling the etiopathogenesis of Hirschsprung's disease. Journal of Pediatric Gastroenterology and Nutrition, 21: 478-479, 1995.