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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02DE000406-01
Application #
2449485
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1999-03-01
Project End
2004-02-29
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Dentistry
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Baev, Didi; Rivetta, Alberto; Vylkova, Slavena et al. (2004) The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5. J Biol Chem 279:55060-72
Wunder, David; Dong, Jin; Baev, Didi et al. (2004) Human salivary histatin 5 fungicidal action does not induce programmed cell death pathways in Candida albicans. Antimicrob Agents Chemother 48:110-5
Dong, J; Vylkova, S; Li, X S et al. (2003) Calcium blocks fungicidal activity of human salivary histatin 5 through disruption of binding with Candida albicans. J Dent Res 82:748-52
Li, Xuewei S; Reddy, Molakala S; Baev, Didi et al. (2003) Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5. J Biol Chem 278:28553-61
Baev, Didi; Rivetta, Alberto; Li, Xuewei S et al. (2003) Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Infect Immun 71:3251-60
Baev, Didi; Li, Xuewei S; Dong, Jin et al. (2002) Human salivary histatin 5 causes disordered volume regulation and cell cycle arrest in Candida albicans. Infect Immun 70:4777-84
Baev, D; Li, X; Edgerton, M (2001) Genetically engineered human salivary histatin genes are functional in Candida albicans: development of a new system for studying histatin candidacidal activity. Microbiology 147:3323-34
Edgerton, M; Koshlukova, S E (2000) Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva. Adv Dent Res 14:16-21
Edgerton, M; Koshlukova, S E; Araujo, M W et al. (2000) Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob Agents Chemother 44:3310-6
Koshlukova, S E; Araujo, M W; Baev, D et al. (2000) Released ATP is an extracellular cytotoxic mediator in salivary histatin 5-induced killing of Candida albicans. Infect Immun 68:6848-56