Department of Pathology & Laboratory Medicine

Judith Rhodes, Ph.D.University of California, Los Angeles, Ph.D., 1980

The long-term goal of the research in Dr. Rhodes' laboratory is to understand the pathogenesis of fungal infections. The model disease being studied is invasive aspergillosis, an often fatal infection of immunocompromised patients caused by the ubiquitous organism Aspergillus fumigatus. Dr. Rhodes and her collaborators have centered their studies on two pathways involved in cell-signalling, a Ras GTPase pathway and the protein kinase A pathway. Ras proteins are molecular switches that regulate down-stream targets, such as MAP kinases. RasB is a unique ras protein that is specific for filamentous fungi. It appears to regulate invasive growth of the organism by aiding in the maintenance of polarity and selection of branch points. Mutants lacking rasB are hypovirulent in a murine model of invasive aspergillosis. The protein kinase A (PKA) pathway is involved in the stress response, and mutants with unregulated PKA activity produce conidia that are hypersensitive to oxidative damage. This phenotype also results in decreased virulence. Phosphoproteomics is being used to define the direct and indirect targets of the type I and II catalytic subunits of PKA. The overall goal of these studies is to understand some of the mechanisms that the organism uses to cause disease, so that effective ways to combat them can be identified.

Recent Publications:

1. Oliver, B.G., J.C. Panepinto, D.S. Askew, and J.C. Rhodes: Cyclic AMP alteration of growth rate of Aspergillus fumigatus and A. niger is carbon source dependent. Microbiology 148:2627-2633, 2002.
2. Panepinto, J.C., B.G. Oliver, T.W. Amlung, D.S. Askew, and J.C. Rhodes: Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation. Fung. Genet. Biol. 36:207-214, 2002.
3. Panepinto, J.C., B.G. Oliver, J.R. Fortwendel, D.L.H. Smith, D.S. Askew, and J.C. Rhodes: Deletion of the Aspergillus fumigatus gene encoding the ras-related protein RhbA reduces virulence in a model of invasive pulmonary aspergillosis. Infect. Immun. 71:2819-2826, 2003.
4. Fortwendel, J.R., J.C. Panepinto, A.E. Seitz, D.S. Askew, and J.C. Rhodes: Aspergillus fumigatus rasA and rasB regulate the timing and morphology of asexual development. Fung. Genet. Biol. 41:129-139, 2004.
5. Fortwendel, J.R., W. Zhao, R. Bhabhra, S. Park, D.S. Perlin, D.S. Askew, and J.C. Rhodes: A fungal-specific Ras homolog contributes to hyphal growth and virulence of Aspergillus fumigatus. Eukaryot. Cell 4:1982-1989, 2005.
6. Zhao, W., J.C. Panepinto, J.R. Fortwendel, L. Fox, B.G. Oliver, D.S. Askew,
   and J.C. Rhodes: Deletion of the regulatory subunit of protein kinase A in
   Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and
   virulence. Infect. Immun. 74:4865-4874, 2006.
   

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Cincinnati, Ohio 45267-0529 ; (513) 558-4500