Molecular & Cellular Biology Program email@example.com University of Iowa 357 Medical Research Center Iowa City, IA 52242-1182 Phone: 319-335-7748 Fax: 319-335-7656
Regulation of lymphocyte development and function
Asthma and other allergic diseases are driven by excessive helper T cell responses to antigen. Thus, helper T cells are attractive targets for new therapeutics. One long-term objective of my lab is to define intracellular signaling pathways that regulate expression of the allergy-promoting cytokines IL-4, -5 and -13 by helper T cells. In previous work, we showed that the peptidyl-prolyl isomerase cyclophilin A (CypA) is a regulator of helper T cell responses. CypA is an enzyme that catalyzes isomerization of peptide bonds adjacent to proline residues. Such catalytic events are known to act as “switches” that regulate protein function via conformational changes. Mice lacking CypA develop inflammation containing eosinophils and mast cells, which both have key roles in allergic responses. Helper T cells lacking CypA overproduce IL-4, -5 and -13 and show increased activation of the key signaling molecule phospholipase C-gamma1 (γ1). These results indicate that CypA functions to repress signal transduction events in helper T cells. Current work is focused on defining the molecular targets of CypA. To achieve this, we are employing molecular biology, biochemistry and mouse models for asthma and other human diseases.
A second topic of study is a novel mutant mouse called Justy. Justy mice lack mature B cells, owing to a block at an early stage of B cell development. The mutation in Justy mice affects a novel transcription factor that likely functions as a modifier of chromatin structure. Current work is focused on determining the function of this protein during B cell development and identifying its downstream target genes.
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