HISTATIN RECEPTORS AS DRUG TARGETS FOR ORAL CANDIDIASIS

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This is a new application for an Independent Scientist Award (K02) for Dr. Mira Edgerton, and it accompanies the already funded R01DE12159 grant. Dr. Edgerton has a D.D.S. degree, specialty training in prosthodontics, and a Ph.D. in Oral Biology. She is an Assistant Professor in the Departments of Restorative Dentistry and Oral Biology at the State University of New York at Buffalo (SUNYAB). Dr. Edgerton's research has focused on characterizing the structural elements of salivary histatins required for candidacidal activity as well as the cellular mechanism of action of histatins with Candida albicans. Her work has identified a C. albicans membrane protein (HstBP) which is a yeast receptor protein of the histatin candidacidal pathway. The current research project will clone and sequence the C. albicans HstBP gene and examine its expression as a virulence or resistance factor in yeast from HIV-oropharyngeal candidiasis patients. Dr. Edgerton's immediate goals are to use the most current techniques in yeast molecular genetic to identify mechanisms of C. albicans pathogenicity in the oral cavity. Her long range goals are to define the molecular basis of virulence, pathogenesis and drug resistance of C. albicans in order to develop better treatment modalities for local and systemic candidiasis. Achievement of these goals is possible only through acquisition of an in-depth background in yeast molecular genetics and knowledge of the most current systems fir eukaryotic genetics. Dr. Edgerton's scientific career would be advanced through this additional training and experience. The research environment in the Department of Oral Biology at SUNYAB in combination with experiences in the laboratories of other yeast molecular geneticists is excellent for development of the research career of Dr. Edgerton. However, her clinical teaching duties limit the time available to her for acquiring these additional research skills. This ISA application is to obtain salary support to release Dr. Edgerton from her clinical teaching and committee responsibilities in order to devote 80% of her full time professional effort to research activities. This award would provide her the opportunity to extend her background in yeast biology to the molecular level and apply this new expertise to studies of virulence and pathogenesis of oral and systemic candidiasis.