Mechanisms and regulation of IgE-dependent mast cell activation

Allergic diseases such as asthma, rhinitis or atopic dermatitis have reached epidemic proportions worldwide. Mast cells play a central role in allergic inflammation. This is because allergen binding on mast cells initiates a cascade of signaling events leading to excessive secretion of biologically potent mast cell mediators. Accordingly, understanding of mechanisms involved in controlling mast cell mediator secretion is essential for the development of effective therapy for the treatment of allergy and asthma. We recently identified a novel molecule, Rcan1 which was not previously associated with mast cells, as a potent endogenous inhibitor of mast cell activation. However, how Rcan1 inhibits allergen-induced mast cell mediator secretion is still unclear. In this application, we will use biochemical and genetic approaches (1) to investigate the molecular targets of Rcan1 in mast cells, (2) to investigate how Rcan1 is regulated in mast cells and (3) to determine the significance of Rcan1 in the development of asthma.