Klutts, J. Stacey, M.D./Ph.D.

Research in 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.

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. To study cell wall synthesis, we are taking three complementary approaches. 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. We are also taking a forward genetic approach with the development of a mutagenesis library in A. fumigatus that will be screened for strains with cell wall defects or with the biochemical assays discussed above. Lastly, we are systematically deleting genes in A. fumigatus that we hypothesize are involved in cell wall synthesis and are studying the cell wall structures and phenotypes of these knockout strains in detail.