We aim to unravel the biological heterogeneity of CD and UC using genetic, genomic and immunologic profiling of patient blood and stool samples and a subset with intestinal biopsies/surgical specimens, with a particular focus on incident cases of CD and in longitudinal studies of response to therapy in CD and UC. This enables us to look at “baseline” heterogeneity as well as heterogeneity in the context of a “stimulus” – molecularly targeted therapies – and to identify and validate genetic, genomic, immunologic markers with predictive potential.
Genetic risk scores developed in ~35,000 IBD patients demonstrate that that ileal and colonic Crohn’s disease are at least as genetically distinct from each other as they are from ulcerative colitis (Left Panel). Serum proteomics support the hypothesis that disease location is an intrinsic aspect of a patient’s disease (in part genetically determined) and the complex set of circulating cytokines, chemokines, growth factors etc.associated with CD reflect the complex interactions between immune, epithelial and mesenchymal cells (Middle Panel). Serum metabolomics in the same patients has enabled the identification of a set of six lipid metabolites that is sufficient to build a model with very beneficial sensitivity and specificity performance. (Right Panel)
Selected publications:
Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location. Boucher G, et al. Inflamm Bowel Dis. 2021 Jun 9:izab123. doi: 10.1093/ibd/izab123.. PMID: 34106269
Comprehensive and Reproducible Untargeted Lipidomic Workflow Using LC-QTOF Validated for Human Plasma Analysis. Forest A, et al. J Proteome Res. 2018 Nov 2;17(11):3657-3670. doi: 10.1021/acs.jproteome.8b00270. Epub 2018 Oct 10. PMID: 30256116
Biomarker-guided stratification of autoimmune patients for biologic therapy. Ivison S, et al. Curr Opin Immunol. 2017 Dec;49:56-63. doi: 10.1016/j.coi.2017.09.006. Epub 2017 Oct 17. PMID: 29053992
Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Cleynen I, Boucher G, et al. Lancet. 2016 Jan 9;387(10014):156-67. doi: 10.1016/S0140-6736(15)00465-1. Epub 2015 Oct 18. PMID: 26490195