Pathology

  • J. Stacey Klutts, MD, PhD
    Research Laboratory

    Contact Information
    Phone: 319-158-3589, Ext 3589
    223 VA Health Care System

    Research Program Description

    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)