|DUKE MYCOLOGY RESEARCH UNIT
The Duke University Mycology Research Unit is a cohesive and interactive group of investigators focused on the molecular biology of pathogenic and model fungi. The mycology group was formed in 1994, and with the recent addition of the bacterial research group, served as the focus for the formation of the Center of Microbial Pathogenesis at Duke University.
The Duke mycology group consists of a highly interactive group of investigators, including senior and junior investigators and basic scientists as well as those focusing on clinical aspects of fungal disease. Areas of interest include the molecular determinants of virulence, the evolution of fungi and pathogenic fungi, development of novel antifungal therapies, and genomic analysis. The twelve labs in the mycology group span the medical center and the college of arts and sciences, both clinical and basic science, and represent an excellent training environment for students (undergraduate, graduate, and medical students), post-doctoral fellows, and medical fellows.
Much of the research efforts of the Duke mycology group focus on the model pathogenic fungus Cryptococcus neoformans. This organism is an important pathogen in immunocompromised patients, and also occurs as a primary pathogen in a cohort of patients with no known immunodeficiency. The organism predominantly infects the central nervous system and is the leading cause of fungal meningitis. Research advances that occurred at Duke include the development of a biolistic transformation system and gene disruption approaches, the rabbit model of cryptococcal meningitis, shotgun genomic sequencing for the pathogenic serotype A isolate H99, construction of bacterial artificial chromosome libraries to scaffold the international genome sequencing effort, generation of a meiotic recombinational map, rediscovery of the diploid phase of the life cycle, discovery of the role of haploid fruiting in the sexual cycle, the first report of a serotype A MATa strain, and the analysis of signal transduction pathways that play a central role in mating and virulence.
Additional ongoing studies in the Duke mycology research group focus on a broader collection of model and pathogenic fungi. Rytas Vilgalys and colleagues focus on the evolution of both ascomycetous and basidiomycetous fungi by population genetic approaches, and together with Tom Mitchell, focus on the evolution of pathogenic fungi. John McCusker and colleagues focus on phase variation, quantitative trait analysis, and molecular determinants of virulence in Saccharomyces cerevisiae. Fred Dietrich is devoted to comparative genome analysis for S. cerevisiae, C. neoformans, and the cotton pathogenic ascomycete Ashbya gossypii. John Perfect, Gary Cox, Andy Alspaugh, Bill Steinbach, Aimee Zaas, and Barbara Alexander are infectious disease specialists who are also experts in molecular mycology. Their labs, located in the Duke South Hospital (Perfect, Cox, Alspaugh, Steinbach, and Zaas) and the CARL Building (Alexander) microbiology laboratories focus on molecular determinants of virulence, animal model studies, and the nature of host immune cell-fungal cell interactions, host defenses, clinical mycology, and transplant medicine-related infectious diseases. Joseph Heitman's group studies both S. cerevisiae and C. neoformans as models to understand how all cells sense and respond to their environments via signal transduction cascades. Their studies have revealed conserved MAP kinase, G protein-cAMP, and calcineurin signaling cascades that are required for fungal differentiation and virulence and which can be targeted for therapy. Several other ongoing research projects focus on additional pathogenic fungi, including Candida albicans, Ashbya gossypii, Candida lusitaniae, and Aspergillus fumigatus. Mari Shinohara's group focuses on how dendritic cells (DCs) interpret signals that are triggered by pathogen-associated molecular patterns, how they transmit the information to T cells, and how they ultimately control autoimmunity and resistance against microbial infection. Dennis Thiele's group deciphers how organisms regulate their growth, development and proliferation through establishing and maintaining proper homeostatic control mechanisms.
The Duke mycology group evolved from an initial core of investigators focused on the pathogenic fungus Cryptococcus neoformans and the model yeast Saccharomyces cerevisiae. This group included John Perfect, Joseph Heitman, Tom Mitchell, and Rytas Vilgalys who began collaborative investigations. From this initial core group, two additional faculty members were recruited (John McCusker in 1996 and Fred Dietrich in 2000), and five infectious disease fellows were mentored to independent positions (Andy Alspaugh, Gary Cox, Bill Steinbach, Barbara Alexander, and Aimee Zaas). The most recent additions to the group include Bill Steinbach with a focus on Aspergillus fumigatus virulence and genetics, Barbara Alexander emphasizing mycological infections in transplant recipients, Aimee Zaas on the host determinants of fungal resistance and susceptibility with an emphasison Aspergillus fumigatus, Mari Shinohara with a special focus on understanding mechanisms to develop anti-fungal immunity, and Dennis Thiele with a focus on understanding how stress-responsive genes are activated and how the encoded proteins function in the prevention of disease states.
The DUMRU group is highly interactive and committed to both scientific excellence and the training of young scientists. The group meets monthly for the DUMRU seminar series, at which students, post-doctoral fellows, faculty, and visiting speakers present their findings. The post-doctoral fellows of the twelve groups meet monthly for a lunch series, and the faculty meet for a biweekly lunch series to discuss common interests and collaborative projects. These forums promote a highly interactive community in which collaborative projects between investigators in different laboratories and different departments are common. The proximity of labs in Duke South Hospital, the adjacent CARL and Jones Buildings, the Biology Building, and the Nanaline Duke Building promotes interactions between all of the groups.