Faculty and Research

Joseph Heitman, MD, PhD
James B. Duke Professor and Chair
Director, Center for Microbial Pathogenesis
research biography • lab members • alumni • publications • lab website

Biography:

Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating from the BS-MS program with dual degrees in chemistry and biochemistry with general and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller Universities and worked with Peter Model and Norton Zinder on how restriction enzymes recognize specific DNA sequences and how bacteria respond to and repair DNA breaks and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Biocenter in Basel Switzerland where, in studies with Mike Hall and Rao Movva, he pioneered the use of yeast as a model for studies of immunosuppressive drug action. His studies elucidated the central role of FKBP12 in forming complexes with FK506 and rapamycin that inhibit cell signaling and growth, discovered Tor1 and Tor2 as the targets of rapamycin, and contributed to the appreciation that immunosuppressive drugs inhibit signal transduction cascades that are conserved from yeasts to humans.

Dr. Heitman moved to Duke University in 1992, and is a member of the Department of Molecular Genetics and Microbiology where his studies focus on how cells sense and respond to the environment. Dr. Heitman and colleagues focus on the model and pathogenic yeasts Saccharomyces cerevisiae and Cryptococcus neoformans and other diverse species from the fungal kingdom. Their studies with fungi as genetic models have revealed biological and genetic principles that can be generalized as models for eukaryotic cell and organism function. These include discovering FKBP12 and Tor1/2 as the targets of the immunosuppressive anti-proliferative natural product rapamycin, elucidating central roles of the calcium activated phosphatase calcineurin governing fungal virulence and morphogenesis and antifungal drug action, deciphering how cells sense and respond to nutrients via permeases, G protein coupled receptors, and the Tor signaling cascade, and illustrating how both model and pathogenic fungi sense both the environment and the infected host. In parallel, their studies address the evolution, structure, and function of fungal mating type loci as models for gene cluster and sex chromosome evolution. Their discovery of unisexual mating in fungi and subsequent analysis has implications for how sex might create diversity de novo rather than by simply admixing pre-existing parental genetic diversity. Studies on the evolution of sex are being extended throughout the derived and basal lineages of the fungal kingdom, including the pathogenic Candida and Cryptococcus species complexes, dimorphic and dermatophyte fungal pathogens, and basal fungi including the zygomycetes (Phycomyces, Mucor, and Rhizopus), blastocladiales, and microsporidia. The discovery of an ancestral sex determining locus in the basal fungal lineages involving two HMG domain proteins, SexM and SexP, homologous to the mammalian Sry sex determinant provides insights into both the origins of sex specification and its plasticity throughout the radiation of the fungal and metazoan kingdoms from their last shared common ancestor.

Dr. Heitman is a recipient of the Burroughs Wellcome Scholar Award in Molecular Pathogenic Mycology (1998-2005), the 2002 ASBMB AMGEN award for significant contributions using molecular biology to our understanding of human disease, and the 2003 Squibb Award from the Infectious Diseases Society of America (IDSA) for outstanding contributions to infectious disease research. He has served as an instructor in residence since 1998 for the Molecular Mycology Course at the Marine Biological Laboratory at Woods Hole, MA. Dr. Heitman is an editor for the journals PLOS Genetics, Genetics, PLOS Pathogens (Pearls review editor), Current Genetics, mBio, and Fungal Genetics and Biology; a member of the editorial boards of PLOS BiologyCurrent Biology, Cell Host and Microbe, Eukaryotic Cell, and PeerJ; former editor for PLOS Pathogens (mycology section editor, 2008-2011) and Eukaryotic Cell (2002-2012); an advisory board member for the Fungal Genome Initiative at the Broad Institute, the Fungal Kingdom Genome Project at the Department of Energy Joint Genome Institute, the NIAID Genomic Sequencing Centers for Infectious Diseases, and for the Integrated Microbial Biodiversity Program at the Canadian Institute for Advanced Research (CIFAR); co-chair for the Duke Chancellor's Science Advisory Council (2009-2010); and co-chair/chair for the FASEB summer conference on Microbial Pathogenesis: Mechanisms of Infectious Disease (2011, 2013). He was elected a member of the American Society for Clinical Investigation (ASCI) in 2003, a fellow of the Infectious Diseases Society of America (IDSA) in 2003, a fellow of the American Academy of Microbiology in 2004, a fellow of the American Association for the Advancement of Science (AAAS) in 2004, and to the Association of American Physicians (AAP) in 2006. Dr. Heitman was an investigator with the Howard Hughes Medical Institute from 1992 to 2005. Dr. Heitman served as the director for the Duke University Program in Genetics and Genomics (UPGG) from 2002-2009 (including writing two funded competitive renewals for the T32 NIH training grant and establishing the annual program retreat). He is currently the founding director for the Center for Microbial Pathogenesis having served in this capacity since January 2002, director of the tri-institutional Molecular Mycology and Pathogenesis Training Program (MMPTP), and Chair of the Department of Molecular Genetics and Microbiology (since September 1, 2009). He received an NIH/NIAID MERIT award in 2011 in support of studies on fungal unisexual reproduction in microbial pathogen evolution, and a Duke University translational research mentoring award in 2012.