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Research Interests

Immunology of Reproduction, Cancer Immunology, Molecular Immunology

Research Orientation

Pregnancy is the only natural example of the total acceptance of a foreign tissue graft for many months by a normal healthy person.聽

Research shows that the mother's immune system actively enhances fetal survival by inducing the production of non-specific suppressor cells and immunoregulatory factors that serve to protect the placenta and fetus rather than causing their rejection. It also appears that some cancers grow and avoid immune rejection for some of the same immunological reasons. Our research projects seek to identify the nature, biochemical functions and targets of cellular suppression of maternal rejection reactions during normal pregnancy.聽

We have previously shown that maternal natural killer (NK) cells can cause spontaneous fetal resorption and that modulation of maternal NK activity alters reproductive efficiency. Early embryo loss is associated with a localization of NK cells and activated macrophages at the feto-maternal interface. These cells accumulate in implantation sites that lack immunosuppressive factors. Once present, the activated NK cells release cytokines such as interferon gamma that activate the tissue macrophages to produce cytolytic factors including nitric oxide, oxygen radicals and tumor necrosis factor that disrupt placental development, causing embryo death. Depletion or inactivation of either NK cells or tissue macrophages reduces embryo losses. In most pregnancies, NK cells may initially respond to the feto-placental tissues in a similar manner but are rapidly controlled during normal pregnancy.聽

Natural killer cells are capable of killing a wide spectrum of transformed tumor cells in the absence of any apparent immune response. NK cells are a subpopulation of normal lymphocytes found in the peripheral blood and spleen of all healthy individuals. These NK cells constantly monitor host cells for aberrant activity, killing neoplastic cells that express reduced levels of normal cell surface proteins During the progression of malignant disease, NK activity becomes progressively depressed as the tumor spreads throughout the host. Activation of NK-cells by treatment with NK-selective cytokines may provide a powerful means for increasing host resistance to the development, growth and spread of tumor cells.聽

Another interest concerns the causes of severe eye inflammation, which occur in some patients with uveitis and in 20 to 30% of contact lens users. We have developed simple immunological assays for immune reactivity to the preservatives added to many lens care solutions. Using this immunoassay, we have assessed the allergenic potential of thimerosal and chlorhexidine in laboratory animals immunized to preservative conjugated proteins. We also propose to clinically use this assay to evaluate patient immune status with respect to other lens care products. Because of the protective environment of the eye, ocular tumors are particularly difficult to treat without harming the patients' vision. Conversely, the eye provides a useful site for observing tumor growth and responses to experimental therapies. Using a combination of investigation of ocular histopathology specimens and animal models, the cell biology and immunology of ocular melanomas have been explored.