The overall goal of this proposal is to facilitate the development of Dr.
Aim ee Zaas into an independent investigator in the genetic basis of host-pathogen interaction. Dr. Zaas proposes a structured five-year career development plan, with rigorous research training under the mentorship of Drs. David Schwartz and John Perfect. As an integral part of career development, Dr. Zaas will also pursue formal training in genetics, genomics, and statistical analysis. This training will culminate in a Master's of Health Sciences in Genomics degree. At the conclusion of this award, Dr. Zaas will have gained considerable skills in murine models of fungal infection, identification of the genetic basis of complex traits using computerized murine single nucleotide polymorphism databases and positional cloning, as well as validation of animal model findings in human cohorts. This knowledge can be applied to future investigations of the genetic basis of fungal infection, as well as be used to direct antifungal prophylaxis in high-risk patients. The research plan involves elucidating the genetic basis of susceptibility to the fungal pathogen Aspergillus fumigatus. The genetic basis of host susceptibility to invasive aspergillosis (IA) is poorly understood. Murine models of IA can be used for gene discovery through the availability of murine single nucleotide polymorphism databases and through positional candidate gene discovery. Using robust phenotypic differences between inbred strains of mice in response to A. fumigatus infection, this proposal will identify and characterize genetic polymorphisms related to IA susceptibility in mice and validate these findings in a cohort of human bone marrow transplant donors and recipients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI065837-02
Application #
7091560
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Duncan, Rory A
Project Start
2005-07-15
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$120,585
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
LaFayette, Shantelle L; Collins, Cathy; Zaas, Aimee K et al. (2010) PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog 6:e1001069
Singh, Sheena D; Robbins, Nicole; Zaas, Aimee K et al. (2009) Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog 5:e1000532
Shapiro, Rebecca S; Uppuluri, Priya; Zaas, Aimee K et al. (2009) Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol 19:621-9
Cowen, Leah E; Singh, Sheena D; Köhler, Julia R et al. (2009) Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc Natl Acad Sci U S A 106:2818-23
Zaas, Aimee K; Liao, Guochun; Chien, Jason W et al. (2008) Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet 4:e1000101
Garantziotis, Stavros; Hollingsworth, John W; Zaas, Aimee K et al. (2008) The effect of toll-like receptors and toll-like receptor genetics in human disease. Annu Rev Med 59:343-59
Hollingsworth, J W; Shofer, S; Zaas, A (2007) Successful treatment of Ochroconis gallopavum infection in an immunocompetent host. Infection 35:367-9