The immune system is implicated in a vast array of diseases along a spectrum of hyperinflammatory, hyperimmune, and autoimmune states. Among these diseases, inflammatory bowel diseases (IBDs), comprising Crohn’s disease and ulcerative colitis, are of particular interest in our lab. More than a million individuals in the United States have a form of IBD. These diseases have no known cause, but significant progress is underway in understanding the underlying mechanisms of these disorders. Our current model of IBD is based on a combination of increased genetic risk and an immune system that overreacts to environmental and microbial stresses.

To uncover basic mechanisms of IBD that can be used to develop treatment, our research takes three general and complementary approaches: using insights from human genetics to understand the biological mechanisms underlying disease, using genetic and chemical screens to identify the function of genes implicated in IBD risk, and gathering primary data from patients themselves. These approaches are guided by the lab’s central philosophy, which is to understand compelling biological and clinical questions, and drive innovation through development, optimization, and adaptation of new technologies.

Dr. Xavier is also a leader in the Broad Institute’s efforts to sequence thousands of exomes of IBD patients and healthy individuals in a project funded by the Helmsley Trust.

Genetics and pathways

Among complex diseases, genetics has been particularly successful in the identification of genes/genetic loci associated with risk of IBD. With this rapid progress, however, it has become clear that a major challenge in the study of complex genetic traits is to determine how disease genes and their corresponding alleles exert their influence on the biology of health and disease. Our working model is that alleles associated with predisposition to IBD — and more importantly, protection from IBD — will identify key pathways in the pathogenesis of IBD. We propose that defining these pathways will provide new insights into each disease state.

Khor et al.,


Rivas et al.,

Nat Genet

McCarroll et al.,

Nat Genet

Lassen et al.,


Graham et al.,

Nat Commun