The objective of this study is to identify the root causes of disease, so that we reveal the key targets for more precise and effective therapies for CD and UC in order to improve the quality of life of patients with CD and UC and eventually lead to the cure of these otherwise lifelong debilitating diseases.
Specific Aim 1: Develop patient and control resources that will enhance the Consortium’s capacity to identify genes, genetic variation and biological mechanisms contributing to the pathogenesis of IBD.
Specific Aim 2: Pursue unique haplotype-based analyses in the French-Canadian population and integrate with Whole Exome Sequencing data to identify novel IBD causal variants.
Specific Aim 3: Perform targeted functional studies of putative variants to advance our knowledge of biological impact of protective and predisposing alleles on cellular functions.
The objective of this study is the development of robust and reproducible systems for generating and testing genotype-specific models of immune-epithelium-gut flora functions and interactions. Our strategy is based on human induced pluripotent stem cell (hiPSC) technology that had the potential of generating complex models combining intestinal epithelial cells, a variety of immune cells, as well as components of the intestinal flora, with the epithelial and immune cells being of specific genotypes.
NIDDK R01 Ancillary (K. Jeffrey, Leader; Rioux, PI of subaward)
The overall objective of the present proposal is to utilize multiple resources from the IBD Genetics Consortium to precisely define the roles of SP140 in mediating protective innate and adaptive immunity toward commensal microorganisms, and determine how altered expression of this epigenome reader in patients bearing common or rare variants of SP140 impacts homeostasis in the gut.
Dr. Alain Bitton is Associate Professor of Medicine at McGill University. He completed a clinical research fellowship in Inflammatory Bowel Disease (IBD) at the Beth Israel Deaconess Medical Center, Harvard Medical School from 1994 to 1996. He was the McGill Gastroenterology Residency Program Director from 1997 to 2007. Since 2009 he has been the Director of the Division of Gastroenterology at McGill University and the McGill University Health Centre (MUHC). His research in the field of IBD focuses on the identification of clinical, biologic, psychosocial and genetic predictors of relapse and disease course in IBD.
Ramnik Xavier is the Kurt Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at Massachusetts General Hospital (MGH). He is a core institute member of the Broad Institute of MIT and Harvard where he is the director of the Immunology Program and co-director of the Infectious Disease and Microbiome Program. He is also co-director of the Center for Microbiome Informatics and Therapeutics at MIT.
Mark J. Daly is Director of the Institute for Molecular Medicine, Finland (FIMM) at the University of Helsinki, a Professor of Genetics at Harvard Medical School, Chief of the Analytic and Translational Genetic Unit at Massachusetts General Hospital, and a member of the Broad Institute of MIT and Harvard. In the early days of the Human Genome Project, Daly helped develop the genetic model by which linkage disequilibrium could be used to map the haplotype structure of the human genome. In addition, he developed statistical methods to find associations between genes and disorders such as Crohn’s disease, inflammatory bowel disease, autism and schizophrenia. Daly is considered a pioneer in the field of human genetics, and is amongst the most cited scientists in the field, and one of the top 100 most cited scientists of all time. He was elected to the National Academy of Medicine in 2017.
His research interests focuses in the inflammatory bowel diseases.