Look into the Future
| Research Opportunity | Forecast | |
| Exploration of the genetic basis of inflammatory bowel disease (IBD) and associated syndromes | Identification of unique host-related events underlying IBD pathogenesis and definition of specific patient subsets and therapies relevant to each subset | |
| Definition of the molecular basis of mucosal responsiveness and nonresponsiveness (tolerance) | Identification and manipulation of positive and negative regulators of mucosal responsiveness to prevent or treat IBD | |
| Identification of mucosal proinflammatory and anti-inflammatory cytokines and their mechanism of action and interaction | Development of methods that block proinflammatory and enhance anti-inflammatory cytokines | |
| Definition of the molecular basis of intestinal epithelial cell (IEC) barrier function and repair | Development of pharmacologic, immunologic, and genetic strategies that enhance IEC barrier and immunologic function and allow its restitution following IBD | |
| Acquisition of increased understanding of intestinal microbiota and the host responses they evoke | Identification and manipulation of key "pathogenic" and "protective" bacterial strains to prevent and treat IBD | |
| Definition of the molecular basis of leukocyte and myeloid trafficking pathways | Development of pharmacologic, immunologic, and genetic strategies that enhance IEC barrier and immunologic function and allow its restitution following IBD | |
| Acquisition of increased understanding of intestinal microbiota and the host responses they evoke | Identification and manipulation of key "pathogenic" and "protective" bacterial strains to prevent and treat IBD | |
| Definition of the molecular basis of leukocyte and myeloid trafficking pathways | Development of strategies to block leukocyte and myeloid recruitment to mucosal surfaces during inflammation | |
| Delineation of the effector mechanisms underlying intestinal tissue destruction | Development of substances that inhibit the effector phase of inflammation, including metalloprotease inhibitors and antioxidants | |
| Improvement in the understanding of brain-gut interactions resulting in exacerbations of IBD | Development of therapies directed at the prevention of relapses in IBD relating to emotional storms | |
| Development of pharmacogenomics associated with specific IBD therapies | Determination of improved ability to predict therapeutic responses and toxicities to particular therapies in specific patients | |
| Development of improved methods of gene transfer and delivery of therapeutic macromolecules to mucosal surfaces | Acquisition of methods to target therapies to sites of tissue inflammation and thus to minimize toxicity to noninflamed tissue | |
| Improvement in the understanding of allograft rejection | Facilitation of small intestinal transplantation in cases of irreversible damage of the intestine due to IBD | |
Authors: Richard S. Blumberg, MD, Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School; Warren Strober, MD, Mucosal Immunity Section, National Institutes of Health