Host-Microbial Interactions
DUKE UNIVERSITY MEDICAL CENTER
Center for

HISTORY OF THE CENTER

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 (now, known as the Center for Host-Microbial Interactions) was originally 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 brought together an existing cadre of investigators focused on fungal and bacterial pathogenesis at Duke. The Center continues to provide exceptional recruitment and training opportunities for graduate students, post-doctoral fellows, and faculty in the area of infectious diseases.

Labs within the Center that focus on fungal pathogenesis study 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.

Areas of interest and expertise for labs with a focus on bacterial pathogenesis 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.

Three missions of the Center of Microbial Pathogenesis were established at its inception. First, we sought to create a supportive and interactive atmosphere in which colleagues with a common interest in infectious diseases can interact and collaborate. Second, we sought 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 sought 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 recruited many 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 has historically been 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.

Current and emeritus members of 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 continue to 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.

Joseph Heitman
Director Emeritus, Center for Microbial Pathogenesis