Bruce Klein, MD

Portrait of Bruce Klein, MD
4303 MSB
1550 Linden Drive
Madison, WI 53706
(608) 263-9217
Focus Groups: 
MD, Boston University
Research Summary: 
The Klein laboratory is a molecular medical mycology research group with two broad areas of focus: fungal pathogenesis and immunology.
Research Detail: 

Our primary research interest is the pathogen Blastomyces dermatitidis, a thermally dimorphic fungus endemic in Wisconsin and the Mississippi, Ohio, and Missouri river valleys. Blastomyces is a primary human pathogen and is a useful model for the other pathogenic dimorphic fungi such as Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasiliensis, Sporothrix schenckii, and Penicillium marneffei, Blastomyces exists as a mold in the soil but transitions to a yeast form at 37°C. Infection occurs when the spore or mold form is inhaled to the lungs. Once in the lungs, transition from the spore to the yeast form is required for disease progression. We are interested in the molecular mechanisms that govern the transition of the mold to the yeast form with the goal of developing novel anti-fungal therapies.

In order to further address the burden of fungal disease, we have developed a vaccine strain of Blastomyces. Another focus of our research program is to understand the mechanism of vaccine-induced immunity to Blastomyces and other fungal pathogens. We investigate both the innate and adaptive response to Blastomyces using fungi that we have engineered to express model antigens. Furthermore, we examine the recognition of fungal surface components (such as the virulence factor BAD-1) by the innate immune system and examine the inflammatory consequences in the host. By understanding the immunological mechanism of vaccine-induced protection we aim to produce effective and long-lasting vaccines against fungal pathogens.

The multiple projects in the lab address common questions in pathogenesis and immunology: what are the mechanisms of fungal virulence, how does the host-pathogen interaction define the progression of infection and disease, how does the immune system respond to fungal infection, and what are the key immunological steps required for vaccine induced immunity to fungal pathogens?

Selected Publications: 
Nanjappa, S.G., Heninger, E., Wüethrich, M., Sullivan, T. & Klein B.S. Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice. J. Clin. Invest. 122(3), 987-99 (2012).
Rocco, N.M., Carmen, J.C. & Klein B.S. Blastomyces dermatitidis yeast cells inhibit nitric oxide production by alveolar macrophage inducible nitric oxide synthase. Infect Immun. 79(6):2385-95 (2011)
Wüethrich, M., Gern, B., Hung, C.Y., Ersland, K., Rocco N., Pick-Jacobs J., Galles, K., Filutowicz, H., Warner, T., Evans, M., Cole, G. & Klein, B.S. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J. Clin. Invest. 121(2), 554-68 (2011).
Ersland K.K, Wüethrich, M., Klein, B.S. Dynamic interplay among monocyte–derived, dermal, and resident lymph node dendritic cells during the generation of vaccine immunity to fungi. Cell Host & Microbe, 7(6):474-87 (2010).
Gauthier, G.M., Sullivan, T.D., Gallardo, S.S., Brandhorst, T.T., Vanden Wymelenberg, A.J., Cuomo, C.A., Suen, G., Currie, C.R. & Klein, B.S. SREB, a GATA transcription factor that directs disparate fates in Blastomyces dermatitidis including morphogenesis and siderophore biosynthesis. PLoS Pathog. 6(4), e1000846 (2010).
Wüthrich M, Kraejun T, Legendre A, Klein BS. Safety and immunogenicity of a live attenuated vaccine strain of Blastomyces dermatitidis. Submitted.
Krajaejun T, Gauthier GM, Wuethrich M, Sullivan TD, Klein B. The Blastomyces dermatitis yeast phase specific gene bys1 regulates morphogenesis, but not virulence. Submitted.
Meece J, Anderson J, Klein B, et al.. Genetic diversity in Blastomyces dermatitidis: implications for PCR detection in clinical and environmental samples. Submitted.
Pfister JR, Archer JR, Hersil S, et al. A large non-rural point source outbreak of blastomycosis near a yard materials collection site. Submitted.
Cooney N, Klein B. Adaptation to environmental stress in pathogenic fungi. Curr Opin Microbiol 2008,11:511-6.