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The Geha Laboratory investigates primary immunodeficiency diseases and allergic diseases. 

Primary Immunodeficiencies

We discover and investigate novel genetic mutations which cause PIDs in collaboration with the laboratory of Dr. Janet Chou. 

 

PID cases are collected from collaborators in 30 centers worldwide who are members of the ICID research network (www.icidnetwork.org). Patient samples are screened for mutations in known PID genes by targeted next generation sequencing (NGS). Patients who harbor no mutations in known PID genes are studied by whole exome sequencing (WES).  We perform functional studies on patient samples, cell lines and mouse models generated using CRISPR-Cas9 technology. This allows us to understand the novel mechanisms of disease. We have discovered a number of novel gene defects that cause PID including  CD40L, SH2D1A, TACI, WIP, DOCK8, LRBA, MALT1, TFR1, DOCK2, RELA, NEIL3, and IFNAR1. Several additional novel genes are currently under investigation.

The Ion Torrent GeneStudio Ion Chef system  automatizes DNA sample preparation for Next Generation Sequencing.

The DOCK8/WIP/WASP Complex 

Mutations in the WASP gene cause Wiskott-Aldrich Syndrome. We have identified WIP as a chaperone for WASP that also links WASP to DOCK8 in a trimeric complex. Our recent work demonstrates that this complex plays a critical role in T and B cell activation, immune synapse formation, T regulatory cell function, and  the maintenance of immunological tolerance. Ongoing work aims at elucidating the mechanisms of food allergy and eczema in DOCK8 deficient patients.

WT

DOCK8-/-

Images of CD4+ T cells from WT and DOCK8-/- mice plated on a superantigen treated endothelial cell monolayer, and stained for Phalloidin (green), and pCasL (red). Orange indicates merging.

Atopic Dermatitis

Atopic Dermatitis (AD) is an allergic skin inflammation that affects over 20% of children. The Geha lab established a mouse model of AD elicited by epicutaneous (EC) sensitization of tape-stripped skin with antigen. This model shares key clinical immunological, histological and features with AD, including the development of airway reactivity in response to inhaled antigen challenge, and of anaphylaxis in response to oral antigen challenge. This has provided the first experimental demonstration of the atopic march. We have used this model to investigate the role of mechanical skin injury, innate immune cells, cytokines, transcription factors, chemokines, and eicosanoids in the development of AD. Current efforts are focused on understanding the mechanism by which mechanical skin injury elicits a Th2 response to cutaneously encountered antigens  and promotes food anaphylaxis. 

Science Immunology  cover featuring  our  publication "RORa positive T reg cells curb allergic skin inflammation".