HISTATIN RECEPTORS AS DRUG TARGETS FOR ORAL CANDIDIASIS

这是Mira Edgerton博士申请独立科学家奖（K02）的新申请，它伴随着已经资助的R01DE12159拨款。Edgerton博士拥有口腔医学博士学位，口腔修复学专业培训和口腔生物学博士学位。她是纽约州立大学布法罗分校（SUNYAB）修复牙科和口腔生物学部门的助理教授。Edgerton博士的研究主要集中在描述唾液组蛋白活性所需的结构元素，以及组蛋白与白色念珠菌作用的细胞机制。她的工作已经确定了一种白色念珠菌膜蛋白（HstBP），这是一种酵母受体蛋白的组蛋白念珠菌途径。目前的研究项目将克隆和测序白色念珠菌HstBP基因，并检测其作为毒力或耐药因子在hiv -口咽念珠菌病患者酵母菌中的表达。Edgerton博士的近期目标是利用酵母分子遗传学的最新技术来确定口腔中白色念珠菌致病性的机制。她的长期目标是确定白色念珠菌的毒力、发病机制和耐药性的分子基础，以便为局部和全身念珠菌病开发更好的治疗方法。这些目标的实现只有通过酵母分子遗传学的深入背景和真核遗传学最新系统的知识才能实现。通过这种额外的培训和经验，Edgerton博士的科学事业将得到推进。SUNYAB口腔生物学系的研究环境，加上其他酵母菌分子遗传学家在实验室的经验，对Edgerton博士的研究生涯发展非常有利。然而，她的临床教学职责限制了她获得这些额外研究技能的时间。这项ISA申请是为了获得薪水支持，以免除Edgerton博士的临床教学和委员会职责，以便将80%的全职专业精力投入到研究活动中。该奖项将为她提供机会，将她在酵母生物学的背景扩展到分子水平，并将这一新的专业知识应用于口腔和全身念珠菌病的毒力和发病机制的研究。

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.