Raif Geha Laboratory | Overview
The Geha Laboratory aims to understand how perturbations in the immune system result in human disease. We focus on two main areas of investigation:
- Mechanisms underlying primary immunodeficiencies.
Primary immunodeficiencies (PIDs) constitute an increasingly diverse group of disorders with a growing number of phenotypes and molecular defects. We have a long-standing interest in the role of the actin cytoskeleton in host immunity. The Geha laboratory cloned the WASP partner WIP, defined the WIP/WASP complex, and its role in linking the TCR to the actin cytoskeleton in blood cells. A major interest of the lab is the interaction between WIP and DOCK8, an adaptor protein critical for B cell activation downstream of Toll-like receptor activation and the maintenance of immunologic tolerance.
- Mechanisms underlying allergic skin Inflammation, eczema vaccinatum (EV) and food allergy in atopic dermatitis (AD).
AD is an allergic skin inflammation of the skin that affects more than 20% of children. The lab established a mouse model of AD elicited by epicutaneous (EC) sensitization that shares several key immunologic, histological and clinical features with AD, including the development of airway reactivity in response to inhaled antigen inhalation, the first experimental demonstration of the atopic march. This model has now been adapted by a number of laboratories for the study of the pathogenesis of AD. Using this model, we have elucidated the role of mechanical skin injury, skin innate immune cells, cytokines, transcription factors, chemokines, and eicosanoids in the development of AD. We have established murine models for EV and demonstrated that the cytokine IL-17A promotes vaccinia virus growth and IL-17A neutralization protects from EV. Our studies have had important implications for the understanding, prevention, and treatment of AD.
We have demonstrated how mutations in multiple genes, including CD40L, TACI, MALT1, TFRC, and LRRC8A, result in impaired host immunity. Dr. Geha spearheads an international consortium of physicians and scientists committed to the diagnosis and treatment of patients with PIDs. By integrating genomic techniques, functional immunologic assays, and murine models of human disease, the lab has identified novel genetic causes of PIDs and elucidates the mechanisms underlying these diseases. Learn more on our website or use the contact information below.
Boston Children's Hospital
1 Blackfan Circle
Karp 10th Floor
Boston, MA 02115