Associate Professor of Internal Medicine
Associate Professor of
Anatomy and Cell Biology
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PhD, Columbia University
Post Doctoral, Columbia University College of Physicians and Surgeons
Education/Training Program Affiliations
Biosciences Graduate Program
Interdisciplinary Graduate Program in Immunology
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program
"Asthma and other allergic reactions are triggered by excessive helper T cell responses to antigen; thus these cells are attractive targets for new therapeutics. One long-term objective of our lab is to define specific intracellular signaling events that control production 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 alters the structure of peptide bonds adjacent to proline, and may thus regulate protein function by catalyzing conformational changes. Mice lacking CypA develop inflammation containing eosinophils and mast cells, which both have key roles in allergy. Helper T cells lacking CypA overproduce IL-4, -5 and -13 and show increased activation of the key signaling molecule phospholipase C-gamma1 (PLC?1). A known regulator of PLC?1 is Itk, a tyrosine kinase involved in the control of IL-4 expression. CypA interacts with a proline residue in Itk; this interaction promotes Itk self-association, which may downregulate Itk activity, and also inhibits contacts between Itk and factors that promote PLC?1 activation. Based on these findings, our central hypothesis is that CypA functions as repressor of Itk, thus limiting cytokine expression by helper T cells. We are employing molecular biology, protein-protein interaction analysis and retroviral gene delivery into T cells to dissect the functional relationship between CypA and Itk and its impact on downstream signaling pathways.
A second topic of study is a novel mutant mouse called Justy. These mice lack mature B cells, owing to a block at an early stage of B cell development. The mutation causes premature translational termination of a protein with homology to Sin3A, the core component of a protein complex that regulates chromatin. Our work is focused on determining the function of this protein during B cell development."
Date Last Modified: 07/31/2013 -