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Immunology

Research

Dr. Margaret Hostetter studies the pathogenesis of pneumococcal and candidal infections. Dr. Hostetter focuses on the genes encoding the virulence factors in these two infections, and the mechanisms by which these pathogens elude complement-mediated host defense. In work with Candida albicans, members of the Hostetter laboratory have shown that a superantigen is cleaved from the amino terminus of the candidal protein Int1p in the presence of heparin concentrations equivalent to those in intravascular catheters. A monoclonal antibody recognizing the superantigenic peptide inhibits T cell activation, cytokine release, and Vß expansion of human T lymphocytes.

Heparin binding sites on Int1p are being mapped. A separate series of studies has indicated that C. albicans invades intestinal epithelium by cleaving inter-junctional proteins. In work with Streptococcus pneumoniae, the laboratory characterized the functions of the conserved pneumococcal cell wall protein CppA, which degrades the C3 ß-chain, inhibits C3-mediated opsonophagocytic killing, and serves as a protective antigen in nasal immunization studies.

Dr. Jose Calderon is studying the effect of facilitated communication between the asthma-allergy specialist and the primary care provider in the outcome of treatment of high-risk asthma in minority children at the Hill Health Center and the Fair Haven Health Center. He is working to translate specialty asthma care into the primary care setting in underserved patient populations.

Dr. Ramsay Fuleihan is studying molecular basis and therapy of primary (congenital) immunodeficiency diseases, including ontogeny of lymphocyte development and function. The Fuleihan laboratory, in collaboration with the Clifford Bogue, M.D. laboratory, discovered that the homeobox gene Hhex plays a critical role in B lymphocyte development, and is pursuing the investigation of the regulation of Hhex expression in B lymphocytes by transcription factors that are critical for B lymphocyte development. In addition, the Fuleihan laboratory continues to investigate the biology of CD40 ligand, the gene defective in the X-linked hyper IgM syndrome in order to develop a model for gene therapy of this disease. The Jeffrey Modell Foundation has established a Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies at Yale, directed by Dr. Fuleihan. This will include a three-year awareness campaign for immunodeficiency diseases in Connecticut, New York and New Jersey.