This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this research project is to study the role of GPI proteins (cell surface proteins) of the fungus C. albicans, in interacting with endothelial cells. Our hypothesis is that the interactions of C. albicans with endothelial cells during the process of hematogenous dissemination are central to the pathogenesis of candidiasis. Additionally interactions of the fungus with neutrophils is central to the ability of the organism to escape host immune response. Overexpression of cell surface proteins has the capacity to modulate these interactions with endothelial cells and neutrophils (the major defense mechanism against hemtogenously disseminated candidiasis). This work is important because the mortality of patients with candidiasis ranges between 30% to 50%, even with currently available therapy. For the proposed studies, the endothelial cells will be harvested from the veins within human umbilical cords and grown in tissue culture. The umbilical cords will be obtained after normal vaginal births from uninfected donors. No information about the mother or baby will be collected. The umbilical cord blood will not be collected. We anticipate that we will need a minimum of 50 umbilical cords for the duration of the study. For neutrophil samples, blood will be collected from volunteers donors in our division after signing an informed consent form. At no time we will connect the results of the assay the neutrophils used for with the identity of the donor. Therefore, we are asking for a wavier of PHI. Ten samples of blood will be collected from donors.
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