The increasing burden of fungal disease in the world combined with the emergence of treatment resistant organisms is an alarming challenge to medicine and human health.
The Klein laboratory is a molecular medical mycology research group with two broad areas of focus: fungal pathogenesis and immunology.
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?
Current Projects
- Mechanisms of phase transition in dimorphic fungi
- Mechanisms of vaccine induced immunity to fungi
- Innate and adaptive immune responses to fungi
- Characterization of host-pathogen interactions in fungal infections
- Targeted development of novel anti-fungal compounds