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K. Mark Ansel
Allergy and asthma are driven by Th2 cytokines. We use biochemistry, cell biology, and mouse genetics to investigate the regulation of the cytokine genes, and we aim to extend our work to explore how chromatin remodeling and regulatory RNAs contribute to the pathogenesis of human asthma.
Other Research in Dr. Ansel's lab:
Development and Differentiation • Immune Regulation
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Hal Chapman
My lab is currently interested in mechanisms of antigen presentation as they relate to allergy and autoimmunity. We are currently pursuing two questions in this area: How is endosomal acidification, and hence endosomal protease activity, regulated in dendritic cells ? This question addresses the signaling determinants of assembly of vacuolar ATPase and MHC class II peptide in single endosomes. And secondly how are carbohydrate coats of allergens processed in dendritic cells, and is this a point of dysregulation in allergy ? Recent studies point to the carbohydrate coat of certain allergens/pathogens as both potential CD1 antigens for NKT cells and as modulators of antigen processing relevant to MHC class II peptide loading. We are addressing both of these questions with ex vivo models of endosomal peptide loading and T cell activation.
Recent relevant publications:
Yang H, Kala M, Scott BG, Goluszko E, Chapman HA, Christadoss P. Cathepsin S Is Required for Murine Autoimmune Myasthenia Gravis Pathogenesis. J Immunol 2005; 174: 1729-1737.
Chapman HA. Endosomal proteases in antigen presentation. Curr Opin Immunol. 2006 Feb;18(1):78-84.
Other Research in Dr. Chapman's lab:
Diabetes and Autoimmunity • Inflammation
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David Erle
Asthma is a complex disease involving many mediators and cell types. We use cell type-specific gene disruption in transgenic mice and other methods to dissect the contributions of specific mediators and cells to various aspects of asthma pathophysiology. Using transgenic mice developed in the lab, we have shown that IL-13 acts directly on airway epithelial cells to produce two key abnormalities characteristic of asthma: mucus metaplasia and airway hyperreactivity (exaggerated airway narrowing in response to bronchoconstrictors). Ongoing work focuses on identifying the molecular mechanisms responsible for these important responses.
Other Research in Dr. Erle's lab:
Immune Receptors and Signaling
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Edward Goetzl
Dr. Goetzl’s laboratory is investigating the expression of vasoactive intestinal peptide (VIP) in T cells and nerves supplying immune organs, as a mechanism for neuroregulation of hypersensitivity reactions. The nanomolar levels of VIP attained at sites of allergic reactions bind to T cell inducible G protein-coupled receptors (VPAC2 Rs) for VIP and signal T cell migration and deviation to a Th2-like phenotype. A T cell-selective VPAC2 GPCR transgenic mouse (TG) has an allergic phenotype, whereas the VPAC2 GPCR knock-out (K/O) mouse has increased delayed-type hypersensitivity, but no detectable allergy. Several carboxyl-terminal deletion mutants of VPAC2 have been identified in T cells that also favor deviation of CD4 T cells to the Th2 phenotype. Current studies are directed to defining the mechanisms of immunoregulation of expression of various types of mutant VPAC2 GPCRs and delineating immune responses of VPAC2 TG x OTII and VPAC2 K/O x OTII mice to oral vs. subcutaneous doses of their preferred peptide antigen.
Other Research in Dr. Goetzl's lab:
Immune Receptors and Signaling
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Nigel Killeen
Using a chronic bacterial infection model system, we are studying the immunological basis of vascular remodeling in the airways. Angiogenesis and lymphangiogenesis in this model system depend on immune complexes and what appears to be the direct involvement of specific myeloid cells. We have been focused on determining the identity of the myeloid cells responsible for remodeling the vasculature, while also establishing which factors they secrete to mediate their remodeling effects. This work is relevant to asthma because the remodeling we are studying is characteristic of the remodeling that occurs in asthmatic airways, and it is possible therefore, that the mechanisms we uncover may also be involved in the pathogenesis of asthma.
Other Research in Dr. Killeen's lab:
Allergy and Asthma, Diabetes and Autoimmunity, Development and Differentiation, HIV and Viral Immunity, Immune Regulation, Immune Receptors and Signaling, Immune Response to Microbial Pathogens
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Richard Locksley
Helper T cells and the cytokines IL-4 and IL-13 have been implicated in many aspects of allergy and asthma. The lab uses several mouse models of allergic immunity to study the initiation and maintenance of innate and adaptive Th2 cells that sustain the allergic state by following the fates of cells marked by their expression of various important cytokines.
Other Research in Dr. Locksley's lab:
Development and Differentiation •
Imune Regulation •
Immune Response to Microbial Pathogens •
Inflammation
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Steve Rosen
The Rosen lab is studying the role of the L-selectin adhesion system in asthma. A family of ligands for L-selectin are expressed in asthmatic lungs both on activated blood vessels and airway-associated mucins. The role of these ligands in asthma is being studied in a sheep model of the disease and in humans.
Other Research in Dr. Rosen's lab:
Development and Differentiation • Immune Receptors and Signaling • Inflammation
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Bill Seaman
We are studying the development of asthma in SKG mice, which have a mutation in ZAP70 that renders them susceptible to inflammatory arthritis.
Other Research in Dr. Seaman's lab:
Immune Receptors and Signaling • Tumor Immunology • Diabetes and Autoimmunity • Immune Response to Microbial Pathogen
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Zena Werb
Metalloproteinases regulate cytokine and chemokine activity and shed cell surface receptors. We are studying how metalloproteinases regulate leukocyte behavior in allergic responses.
Other Research in Dr. Werb's lab:
Immune Response to Microbial Pathogens • Inflammation • Tumor Immunology • Development and Differentiation
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