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 Research Group 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?
- 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
The following scholarly articles were published by Department of Pediatrics faculty and staff during January 2020: Altman MC, Beigelman A, Ciaccio C, Gern JE, Heymann PW, Jackson DJ, Kennedy JL, Kloepfer K, Lemanske RF Jr, McWilliams LM, Muehling …February 11, 2020
Congratulations to Bruce Klein, MD, Principal Investigator, and Marcel Wüthrich, PhD, Multiple PI, on the competitive renewal of their National Institutes of Health/National Institutes of Allergy and Infectious Diseases (NIH/NIAID) R01 grant entitled, “Mechanisms of …July 5, 2019
Congratulations to Scott Fites, PhD, and his mentor, Bruce Klein, MD, for their recent fellowship award from the Hartwell Foundation. This 2-year grant, titled “Harnessing a long-lived neutrophil to fight systemic fungal infections,” awards $100,000 …September 1, 2018
Bruce Klein, MD, was recently awarded a 1-year grant for $49,527 from the United States Geological Survey (USGS) National Wildlife Health Center for his project entitled, “The novel method for assessing vaccines against White Nose …September 1, 2018
Congrats to Bruce Klein, MD, on his recent R01 research grant funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID). His 4-year, $1.85 million project is entitled, “Lung epithelial …August 1, 2018
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