George Kobayashi, Ph.D.
Professor of Medicine and Molecular Microbiology

Office: (314) 454-8234
Lab: (314) 362-3163
FAX: (314) 454-5392
E-mail: kobayashi@labmed.wustl.edu

Office: Barnes-Jewish Hospital North, 7th Floor, Kingshighway Bldg., Box 8051
Lab: 261 Barnes Hospital Service Bldg.

Histoplasmosis is the most common respiratory fungus infection in the world.  It is world-wide in distribution and highly endemic in the Ohio and Mississippi Valley regions of the United States.  Our research activities focus on three major projects of the etiologic agent, Histoplasma capsulatum.  They are concerned with:  1)  molecular studies which relate to virulence; 2) host-parasite interaction; and 3) therapy.  This fungus undergoes a morphologic transition from its saprobic multicellular filamentous soil phase to a parasitic unicellular yeast-like phase during the process of infection.  Conversion to the yeast morphology is important in virulence since organisms unable to convert are avirulent.  This process can be reproduced in the laboratory by changing the temperature of incubation from 25 degrees C (filamentous phase) to 37 degrees C (yeast-like phase).  We are interested in elucidating the mechanisms that trigger and control this event since dimorphism in H. capsulatum provides a developmentally regulated model system in which alterations in gene expression during the temperature-induced transition can be studied in a medically important eukaryotic pathogen.  We are also interested in host-parasite interaction and have shown that phagocytosis of H. capsulatum yeasts by murine macrophages produces a defect in macrophage microbicidal activities manifested by inhibition of macrophage respiratory burst activity.  These studies provide clues to understanding the highly characteristic intracellular localization of H. capsulatum yeast within tissue macrophages during infections and also provides an approach to identifying virulence determinants of this fungus.