Our laboratory studies how the immune system maintains tolerance, its ability to defend the body while remaining unreactive to the foods, microbes, and self-tissues it encounters constantly, and how the failure of tolerance gives rise to allergic and autoimmune disease. Our work centers on the regulatory T cell, a specialized population that senses tissue and environmental signals and determines whether the immune response proceeds toward tolerance or inflammation. We study how these cells read their environment, how they are subverted in disease from protective to pathogenic, and how they might be reprogrammed for therapy.
Our work spans human genetics and the gut microbiome. In 2000, we independently identified mutations in FOXP3 as a cause of severe inherited immune dysregulation in humans, work that helped establish FOXP3 as an essential regulator of immune tolerance. Building on this, we have defined how additional genes, including DOCK8, LRBA, and IL4R, govern regulatory T cell function and tolerance in human disease. We found that regulatory T cells can be reprogrammed in tissues to drive, rather than restrain, inflammation, and defined a receptor-based molecular code through which they license distinct inflammatory responses in the lung, brain, and intestine. In the gut, we established that the commensal microbiota is required for oral tolerance to foods, that its disruption promotes food allergy, and that defined beneficial bacteria can restore tolerance through a specific regulatory T cell pathway. A unifying theme runs through this work: Regulatory T cells act as the cellular interface between the organism and its environment, and understanding how they sense and respond to that environment is the basis for a new generation of precision therapies aimed at restoring immune tolerance.
The laboratory combines human genetics, immunology, microbiology, and translational medicine at Boston Children's Hospital and Harvard Medical School. We welcome curious and rigorous scientists interested in working at the interface of mechanistic discovery and clinical translation in allergic and autoimmune disease.