Duke University Medical Center

Fungal Genetics and Biology Genes & Development Molecular Biology of the Cell

The most dramatic impact of medicine and science on human health and longevity over the past century is attributable to reductions in infectious diseases as a result of improvements in water quality and sanitation and the introduction of vaccines and antibiotics. Until recently, many thought that the scourge of infectious diseases had been vanquished, and yet over the past several years there has been an inexorable increase in infectious threats to human health. There have been no more sobering developments in recent history than the AIDS pandemic, the failure to eradicate diseases such as tuberculosis and malaria, and the emergence of new and drug resistant bacterial and fungal pathogens.

The Center for Microbial Pathogenesis was created within the umbrella of the Department of Molecular Genetics and Microbiology to provide a focus on microbial pathogenesis and infectious diseases in two general areas: bacteriology and molecular mycology. Viruses as the agents of infectious disease are the purview of a second center within the Department of Molecular Genetics called the Center for Virology.

The establishment of the Center for Microbial Pathogenesis brings together an existing cadre of investigators focused on fungal and bacterial pathogenesis at Duke. The Center provides exceptional recruitment and training opportunities for graduate students, post-doctoral fellows, and faculty in the area of infectious diseases.

There are currently fourteen labs at Duke focused on fungal pathogenesis that form an interactive group and supportive atmosphere as the Duke University Mycology Research Unit (DUMRU). All fourteen labs are members of the Center for Microbial Pathogenesis, including five labs in the Department of Molecular Genetics and Microbiology (Joseph Heitman, Fred Dietrich, Ana Litvintseva, Tom Mitchell, and John McCusker), five labs in the Division of Infectious Diseases in the Department of Medicine (John Perfect, Gary Cox, Andrew Alspaugh, Barbara Alexander, and Aimee Zaas), one lab in the Division of Infectious Diseases in the Department of Pediatrics (Bill Steinbach), one lab in the Department of Biology (Rytas Vilgalys), one lab in the Department of Immunology (Mari Shinohara), and one lab in the Department of Pharmacology and Cancer Biology (Dennis Thiele).

Studies focus on the molecular determinants of virulence in the basidiomycetous human fungal pathogen Cryptococcus neoformans and employ molecular biology, genomics, animal models, and population genetics. Related studies are in progress in other model and pathogenic fungi, including Saccharomyces cerevisiae, Ashbya gossypii, Candida albicans, Candida lusitaniae, Aspergillus fumigatus, and pathogenic Zygomycetes and Microsporidia and address both host factors important for infection and the unique adaptations that have enabled pathogenic fungi to survive in the harsh environment of the infected host.

The second arm of the Center for Microbial Pathogenesis focuses on bacterial pathogenesis. There are currently fourteen labs in this area of interest. This spans an original core of investigators, including Alejandro Aballay, Jorn Coers, and Raphael Valdivia in the Department of Molecular Genetics and Microbiology, Soman Abraham in the Department of Pathology, Meta Kuehn in the Department of Biochemistry, and Richard Frothingham and Ken Wilson from the Division of Infectious Diseases in the Department of Medicine. These investigators bring a new focus in the use of model systems (worms, yeast) to the molecular analysis of bacterial virulence. These investigators have been joined now by other faculty, including Vance Fowler and Greg Taylor, both from the Department of Medicine, and Joe St. Geme, the chair of the Department of Pediatrics as well as Patrick Seed from the Department of Pediatrics, Dewey McCafferty from the Department of Chemistry, and Sunhee Lee from the Department of Medicine and the Human Vaccine Institute, and David Tobin from the Department of Molecular Genetics and Microbiology. Areas of interest and expertise include the role of vesicles in toxin production and delivery, how bacterial pathogens interact with immune cells, the molecular evolution of virulence in Mycobacteria and the role of the normal flora in health and human disease, the use of model systems approaches including budding yeast cells and the nematode C. elegans, vaccine development and mammalian innate immunity, antibiotic targets and mechanisms of action, how uropathogenic E.coli interacts with the bladder epithelium to persist during acute and chronic infections, and host-pathogen interface and aspects of both innate and adaptive immunity.

The missions of the Center for Microbial Pathogenesis are three. First, we seek to create a supportive and interactive atmosphere in which colleagues with a common interest in infectious diseases can interact and collaborate. Second, we seek to foster a robust training environment for graduate students, post-doctoral fellows, medical students, and medical fellows with an interest in training in infectious diseases research. Third, we seek to recruit additional outstanding faculty to Duke University Medical Center to join us in our quest to understand the molecular nature of the host-pathogen interaction and develop means to intercede for therapy. Since our inception on January 1, 2002, we are delighted to have already recruited several outstanding new colleagues to join us as we focus on bacterial and fungal pathogens, genome and genomic approaches to pathogenesis, and immune control of pathogens.

The Center for Microbial Pathogenesis is well-supported by grants from the NIH, NSF, and other sources, including the Burroughs Wellcome Fund. The mycology group was supported by a Mycology Center Program Project Grant from the NIAID from 1999-2005, and currently administers a tri-institutional training program, the Molecular Mycology and Pathogenesis Training Program (MMPTP), which supports basic science and clinical fellows training in mycology at North Carolina State University, the University of North Carolina in Chapel Hill, and Duke University. Faculty members in the Center have been well-recognized for their achievements, including several that are fellows or members of the American Society for Clinical Investigation (ASCI) (Heitman, St. Geme, Fowler, Alspaugh), the Association of American Physicians (Perfect, Heitman, St. Geme), the American Academy of Microbiology (Mitchell, Perfect, Heitman, St. Geme, Abraham, Vilgalys, Thiele), the fellows program of the American Association for the Advancement of Science (Vilgalys, Heitman, Perfect, Mitchell, St. Geme, Thiele), and the Institute of Medicine (St. Geme). Several investigators have been supported or are currently supported by the Burroughs Wellcome Fund (Kuehn, Cox, Alspaugh, Heitman, Valdivia) two have received the Squibb Award from the Infectious Diseases Society of America (St. Geme, Heitman), two have received the Billy Cooper Award from the Medical Mycology Society of the Americas (Mitchell, Schell), one is a Pew Scholar (Valdivia), three have received the ASM ICAAC Young Investigator Award (Aballay, Fowler, Coers), one has received the ASM Merck Irving Sigal Award (Valdivia), one has received the Pediatric Infectious Diseases Society Young Investigator of the Year Award (Steinbach), one has received the Alexopoulos Prize from the Mycological Society of America (Vilgalys), one has received the IDSA Oswald Avery Award for Early Achievement (Fowler), one has received the Williams Prize at Duke (Fowler), one has received the ASM Dade Behring MicroScan Young Investigator Award (Steinbach), one has received the AMGEN Award from the American Society for Biochemistry and Molecular Biology (Heitman), one has received a MERIT award from the NIH/NIAID (Heitman), two have presented the Division F lecture at the American Society for Microbiology general meeting (Perfect, Heitman), one has served as the chair of Division F of the ASM (Mitchell), and one as councilor for Division F of the ASM (Perfect). Notably, Dr. Perfect received the Duke University Scholar-Teacher of the Year award in 1999.  

In addition, members of the Center serve as editors or editorial board members for the journals Antimicrobial Agents and Chemotherapy, Cell Host and Microbe, Current Genetics, Current Biology, Drug Resistant Updates, Eukaryotic Cell, FEMS Yeast Research, Fungal Genetics and Biology, International Journal of Plant Sciences, Journal of Invasive Fungal Infections, Journal of Clinical Microbiology, Mycopathologia, Medical Mycology, PLoS Biology, PLoS One, Molecular Microbiology and Anti-Infective Agents in Medicinal Chemistry, PLoS Pathogens, Revista Iberoamericana de Micologia, and Virulence. Several faculty participate in teaching at the Woods Hole Molecular Mycology course, held each August at the Marine Biological Laboratory at Woods Hole, MA. Finally, several alumni from the training labs in the Center are now faculty members at institutions throughout the world (Maurizio del Poeta, Mike Lorenz, Christina Hull, JP Xu, Wieland Meyer, Ping Wang, Xuewen Pan, Sun Bahn, Wei-Chiang Shen, James Fraser, Floyd Wormley, Marcello Vallim, Gary Cox, Andy Alspaugh, Robb Cramer, Julian Rutherford, Alex Idnurm, Kirsten Nielsen, Chaoyang Xue, Xiaorong Lin, Timothy James, and Jason Stajich.

We invite you to explore this website, and to contact us if you are interested in further information about the Center for Microbial Pathogenesis at Duke University.

Joseph Heitman
Director, Center for Microbial Pathogenesis

Current Biology Current Biology Molecular Microbiology
Genes & Development Current Genetics Eukarytic Cell
Current Genetics
Current Genetics Current Genetics Springer
Cryptococcus PNAS_2 PNAS_3
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Crypto Book A. fumigatas Book PLoS Cover
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