The CSIBD is a multidisciplinary program to define fundamental mechanisms underlying Crohn’s disease and ulcerative colitis and is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.
Organizing the 111 CSIBD investigators by areas of focus, we can divide the Center into six central themes. Our goal of understanding human IBD is accomplished using six entry points: (1) genetics, (2) microbial interactions, (3) barrier function and epithelial cell biology, (4) innate and adaptive immunity, (5) therapeutics, and (6) systems biology and signal transduction. Clinicians, scientists, and engineers are embedded in each theme.
The Center encompasses 111 investigators at the Massachusetts General Hospital (MGH) and allied institutions pursuing research in a broad spectrum of basic science relevant to IBD. Since its formation 24 years ago, the CSIBD serves as a vehicle to achieve advances in our understanding of these diseases through the study of relevant basic biological processes and the directed study of the diseases themselves.
Research at all levels is driven by a central hypothesis that the major forms of IBD result from the interaction between permissive genetically determined features of the host/patient and luminal bacteria (and possibly other environmental factors) which upregulate and activate mucosal immune and inflammatory pathways without sufficient regulatory controls. The major advances made possible by the CSIBD include the development and characterization of new genetic mouse models of IBD, delineation of mechanisms of lymphocyte activation and leukocyte recruitment to sites of inflammation, characterization of mechanisms of innate immune response, identification of key peptides involved in sustaining mucosal integrity, characterization of the mechanisms of mucosal healing following injury, improved understanding of the regulation of epithelial function, functional mapping of genetic variants in IBD, mucosal immune responses and delineation of the mechanisms of mucosal:microbial interaction.
A major focus of CSIBD research is the coordinated multi-disciplinary study of mechanisms leading to chronic intestinal inflammation and delineation of interactions between environmental factors and different genetic loci. The Center also actively promotes clinical and translational research efforts to apply insights gained in studying various disease mechanisms through its five biomedical cores: the Human Genetics and Microbiome Core, the Morphology Core, the Immunology Core, the Genetic Animal Models Core and the Clinical Core.
The overall goal of the CSIBD is to promote and facilitate research that will yield insight into the causes and pathogenesis of IBD and lead to improved therapeutic approaches. This overarching objective remains unchanged since the inception of the CSIBD in 1991 and has guided the Center through substantial growth and expansion. The Center’s approach to accomplishing this goal also remains consistent: providing research support through biomedical cores and developing an outstanding research base.
The main “engine” of the Center continues to be the biomedical cores, which foster productivity by providing technical and intellectual support for a broad spectrum of basic and applied research in fields that are essential for fundamental progress in understanding these diseases. Equally important is the recruitment and development of investigators in IBD-related research. This is particularly relevant in the field of IBD, in which complex, multifactorial interactions are a constant theme. Molecular biologists, microbiologists, and cell biologists seek to understand intra- and inter-cellular function and communication. At a higher level, immunologists, geneticists, epidemiologists, and genomics researchers drive progress. To this wealth of information, clinicians contribute patient-based insights and gain potential targets for therapeutics. Therapeutic leads are pursued by chemists to feed back into the system, and progress at all levels is driven by computational biologists and technology development, with systems biologists integrating information.
The Center goals are as follows:
- Promote research in basic science areas relevant to better understanding of mucosal immune function and epithelial biology in IBD
- Advance our understanding of gut pathophysiology by examining the gut as a “circuit”: studying the core components of gut intra- and inter-cellular interactions that determine health and disease
- Promote the study of the pathogenesis of IBD
- Promote interactions among scientists exploring diverse fields that share relevance to IBD
- Promote translational IBD research
- Attract basic investigators to the study of IBD and mucosal immunology
- Provide an environment and mechanism to foster development of young investigators focused on IBD