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Phone: 319-158-3589, Ext 3589
223 VA Health Care System
My laboratory primarily focuses on the human pathogenic fungus Aspergillus fumigatus.
This is a ubiquitous environmental mold that can cause a variety of
diseases in humans, including a life-threatening invasive infection in
the setting of immune compromise. Treatment options exist for invasive
aspergillosis, but therapeutic failures are common with mortality rates
as high as 85% in some patient populations. This high mortality rate is
partially due to a paucity of effective anti-fungal drugs to treat
advanced infections. My laboratory is interested in identifying new
anti-fungal drug targets.
Currently, the main focus of the laboratory is to better understand the process of cell wall synthesis in A. fumigatus. Pathogenicity and survival of A. fumigatus in vivo
requires a number of virulence factors, with the ability to generate a
rigid cell wall being one of the most important. Targeting cell wall
synthesis with anti-fungal therapy has been successful in the treatment
of a number of fungal infections. However, identification of additional
drug targets in the pathway of cell wall assembly is hindered by our
limited knowledge of these synthetic mechanisms. My laboratory is taking
three parallel and complementary approaches to identify
enzymes/proteins involved in cell wall synthesis. One aim is to develop
enzymatic assays for monitoring the activity of glycosyltransferase
enzymes likely involved in cell wall synthesis and to use these assays
to purify/identify the corresponding proteins. Second, we are deleting
enzymes that we hypothesize are involved in cell wall synthesis and
studying the resulting deletion strains in detail. Lastly, we are taking
a forward genetic approach with the development of an insertional
mutagenesis library in A. fumigatus that is being screened for strains containing cell wall defects.
Combined, these approaches are aimed at deciphering pathways involved in Aspergillus cell wall synthesis and identification of plausible anti-fungal drug targets within those pathways.
(See complete publications list at PubMed)