understanding the molecular basis of fungal infections

Infectious diseases represent one of the most fascinating, and important, fields of microbiology. The human body is one of the most complex and dynamic environments to which microbes have adapted, and understanding these adaptations is the key to improving treatment. Infections from eukaryotic pathogens, such as fungi, are particularly difficult to treat because of the extensive similarities in cell physiology between fungal and human cells.

My laboratory studies the most important of the fungal pathogens. Candida albicans causes a disseminated bloodstream infection that is fatal in about 40% of cases. For most of us, however, Candida is a normal and harmless part of our microbiota - the community of microorganisms that lives in and on us. The difference between Candida as a deadly pathogen and Candida as a benign commensal is the status of the host's immune system. Infection occurs in people with immunodeficiencies of some kind.

Thus, we are particularly interested in studying the interaction between C. albicans and cells of the immune system, primary phagocytic cells such as macrophages. In vitro, this interaction is extremely dynamic (see figure below). Phagocytosis stimulates a dramatic morphological change, which helps the yeast escape killing by the macrophage. These filaments, or hyphae, are only a small part of this response, however. We have shown that there are equally dramatic changes to cellular physiology and metabolism when C. albicans is confronted with a phagocytic cell. These changes in carbon metabolism, in particular, are critical during infections and we are very interested in the regulatory and signaling networks that control these responses.

SELECTED PUBLICATIONS:

Lorenz MC, Bender JA, Fink GR (2004) Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076 [abstract]

Lorenz MC, Fink GR (2002) Life and death in a macrophage: role of the glyoxylate cycle in virulence. Eukaryot Cell 1:657 [abstract]

Lorenz MC (2002) Genomic approaches to fungal pathogenicity. Curr Opin Micobiol 5:372 [abstract]

Lorenz MC, Fink GR (2001) The glyoxylate cycle is required for fungal virulence. Nature 412:83 [abstract]

Lorenz MC, Pan X, Harashima T, Cardenas ME, Xue Y, Hirsch JP, Heitman J (2000) The G protein-coupled receptor Gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics 154:609 [abstract]

Lorenz MC, Cutler NS, Heitman J (2000) Characterization of alcoholinduced filamentous growth in Saccharomyces cerevisiae. Mol Biol Cell 11:183 [abstract]

[compete list of publications on PubMed]