Our research program is focused on allergic immune responses, which play a role in a variety of diseases such as asthma. We are particularly interested in the cellular dynamics of IgE antibody production and downstream inflammatory responses. In order to understand this complex in vivo biology, we apply a series of sophisticated techniques, such as two-photon microscopy to directly visualize cellular interactions during allergic immune responses.
Other Research in Dr. Ansel's lab:
Immune Regulation • Immune Receptors and Signaling • Inflammation
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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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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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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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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 •
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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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Asthma is regulated by effects of innate and adaptive immune responses on airway smooth muscle and airway epithelial cells. We study how different members of the integrin family expressed on antigen presenting cells, epithelium and smooth muscle modulate these interactions. One goal of this work is to develop new treatments for asthma and other immune-mediated diseases.
Other Research in Dr. Sheppard's lab:
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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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