Enter the text here that is the new abstract information for your application. This section must be no longor than 30 tines of text. .N'.. evidence of the medical significance of this common mould, our understanding of its pathogenic A. fumigatus conidia and germlings and infected host cells in culture (Aim 2). Findings will be yet unknown lineage-specific pathways. Importantly, given the multifactorial nature of this components of the innate imniune system in preventing the establishment of an invasive infection evidence supports the critical role of alveolar macrophage and neutrophils as the essential Invasive aspergillosis (IA) caused priniarity by Aspergillus fumigatus is an emerging source of and neutrophil infections of human cell lines (Aim 1);and mRNA expression profiles of infecting fumigalus host-pathogen interaction. The approaches we will employ are: in vitro macrophage current research field, and our genomic and bioinformatic expertise to characterize the A. profiling methodologies, mammalian cell culture modelling methodologies at the forefront of the specific molecular landmarks of infection. We will combine advanced high throughput expression study of the intact mammalian ex v/vo immune cell-fungal interactions, in order to decipher stage- interaction and the heterogeneity of the susceptible patient population, we the fungal metabolic pathways to iron depletion, alkaline shift, and nitrogen starvation as welt as fumigafus in overcoming the defenses of the immune suppressed human host involve adapting in immune competent mammalian hosts. Our key hypothesis is that mechanisms employed by A. pathogen- mediated events govern the nutcome of an A. fumigalus infection. Accumulated mechanisms morbidity and mortality in devetoped countries including the U.S. Despite the accumulating 'VI is limited. Epidemiological evidence demonstrates that concurrent host- and ilt perform a parallel 3_? o'> N.. a'^ Son o-3 c?? ..- ... :.c yield a wealth of information on the host-pathogen interactions necessary for A. fumiqatus to validated using human primary macrophage and neutrophil cells. Completion of these aims will mount a successful invasive infection. The completion a'. will also illuminate some nf the ... d?? The host response analysis will identify approaches to modulate or augment the therapeutic participating components of the host immune system and reveal the immune components minimize the risk of invasive aspergillosis during and after these treatments. regimens applied concurrently with transplant and other medical interventions insight will direct therapeutic approaches to treating, and diagnosing these invasive infections. necessary to maintain protective immunity against the invading fungus. This hithertn inaccessible ... in order to >.E =.m m'- N'3 ..' 'C3 _.n '-' a.. m._ o'< m-?
Lethal infections by environmental fungi are becoming increasingly common with advances in medical technologies for treatment of cancers and for organ transplants. Therapeutic options for these fungal infections are very limited, and new interventions are urgently needed. This proposal seeks to discover new therapeutic options to treat invasive aspergillosis caused by Aspergillus fumigatus and to identify approaches to minimizing the risk of contracting these infections as a result of these cancer and organ transplant medical procedures.