Joseph Heitman
· James B. Duke Distinguished Professor and Chair, Molecular Genetics and MicrobiologyDuke University · Microbiology and Immunology
Active 1986–2024
About
Joseph Heitman is the James B. Duke Distinguished Professor of Molecular Genetics and Microbiology and the Chair of the Department of Molecular Genetics and Microbiology at Duke University. His research focuses on the sexual reproduction and evolution of microbial pathogens, particularly the human fungal pathogen Cryptococcus, which causes life-threatening infections of the central nervous system in both immunocompromised and immunocompetent hosts. His studies have contributed to defining the sexual cycle involving haploid alpha and a cells, elucidating the molecular basis for antifungal drug action, and exploring the roles of calcineurin in fungal virulence and drug tolerance across multiple pathogenic fungi including Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. Dr. Heitman has participated in and organized fungal genome sequencing projects, including those for Cryptococcus strains, Candida species, and Tremella mesenterica, revealing insights into fungal evolution, mating type loci, and virulence factors. His work on the structure, function, and evolution of the fungal mating type locus has uncovered how these loci influence differentiation and pathogenicity, with detailed models for their evolution paralleling sex chromosomes in plants and animals. Additionally, his research investigates the molecular mechanisms of sexual reproduction, hybrid formation, and population genetics in Cryptococcus, providing understanding of how sexual recombination impacts the evolution and virulence of pathogenic fungi. Dr. Heitman’s contributions extend to elucidating the targets of immunosuppressive drugs like rapamycin, discovering TOR as a key target, and exploring conserved signal transduction pathways from yeast to humans. His career began with undergraduate studies at the University of Chicago, followed by MD-PhD training at Cornell and Rockefeller Universities, where he worked on DNA recognition and repair mechanisms. His postdoctoral work in Basel, Switzerland, with Mike Hall and Rao Movva, pioneered the use of yeast as a model for studying immunosuppressive drug action, leading to the discovery of TOR as the target of rapamycin. Since joining Duke University in 1992, Dr. Heitman has focused on addressing fundamental biological questions and unmet medical needs related to microorganisms, with a particular emphasis on pathogenic fungi and their molecular biology, evolution, and interactions with hosts.
Research topics
- Biology
- Genetics
- Microbiology
- Ecology
- Computer Science
- Immunology
- Geography
- Environmental planning
- Environmental ethics
- Programming language
- Bioinformatics
Selected publications
Proceedings of the National Academy of Sciences · 2023 · 55 citations
- Biology
- Genetics
- Microbiology
isolates recovered from infected mice, providing evidence that mobile elements are likely to facilitate microevolution and rapid adaptation during infection.
Proceedings of the National Academy of Sciences · 2020 · 71 citations
- Biology
- Microbiology
- Genetics
is an important mechanism that enhances microbial adaptation and promotes pathogenesis and drug resistance in the human host.
Proceedings of the National Academy of Sciences · 2020 · 43 citations
Senior authorCorresponding- Biology
- Microbiology
- Genetics
flavohemoglobin. Lastly, we identified an additional 30 genus- and species-specific horizontal gene transfer candidates that might have contributed to the evolution of this genus as the most common inhabitants of animal skin.
Centromere scission drives chromosome shuffling and reproductive isolation
Proceedings of the National Academy of Sciences · 2020 · 81 citations
Senior authorCorresponding- Computer Science
- Biology
- Genetics
The resulting DSBs were repaired in a complex manner, leading to the formation of multiple interchromosomal rearrangements and new telomeres, similar to chromothripsis-like events. The newly generated strains harboring chromosome translocations exhibited normal vegetative growth but failed to undergo successful sexual reproduction with the parental wild-type strain. One of these strains failed to produce any spores, while another produced ∼3% viable progeny. The germinated progeny exhibited aneuploidy for multiple chromosomes and showed improved fertility with both parents. All chromosome translocation events were accompanied without any detectable change in gene sequences and thus suggest that chromosomal translocations alone may play an underappreciated role in the onset of reproductive isolation and speciation.
Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture
mBio · 2020 · 526 citations
- Environmental ethics
- Geography
- Biology
The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been reported to infect vertebrates, 200 of which can be human associated, either as commensals and members of our microbiome or as pathogens that cause infectious diseases. These organisms pose a growing threat to human health with the global increase in the incidence of invasive fungal infections, prevalence of fungal allergy, and the evolution of fungal pathogens resistant to some or all current classes of antifungals. More broadly, there has been an unprecedented and worldwide emergence of fungal pathogens affecting animal and plant biodiversity. Approximately 8,000 species of fungi and Oomycetes are associated with plant disease. Indeed, across agriculture, such fungal diseases of plants include new devastating epidemics of trees and jeopardize food security worldwide by causing epidemics in staple and commodity crops that feed billions. Further, ingestion of mycotoxins contributes to ill health and causes cancer. Coordinated international research efforts, enhanced technology translation, and greater policy outreach by scientists are needed to more fully understand the biology and drivers that underlie the emergence of fungal diseases and to mitigate against their impacts. Here, we focus on poignant examples of emerging fungal threats in each of three areas: human health, wildlife biodiversity, and food security.
Loss of centromere function drives karyotype evolution in closely related Malassezia species
eLife · 2020 · 74 citations
- Biology
- Genetics
species complex through breakage and inactivation.
Recent grants
NIH · $662k · 2001
Structural Biological Development of Fungal-Specific Calcineurin Inhibitors
NIH · $669k · 2014–2022
NIH · $3.0M · 2010
Transdisciplinary Program to Identify Novel Antifungal Targets and Inhibitors
NIH · $3.6M · 2015–2020
The Genetic Architecture of Virulence in Cryptococcus neoformans
NIH · $186k · 2017–2017
Frequent coauthors
- 484 shared
Sheng Sun
Duke Medical Center
- 311 shared
María E. Cárdenas
Duke Medical Center
- 243 shared
Anna Floyd Averette
- 230 shared
Vikas Yadav
Duke University Hospital
- 220 shared
John R. Perfect
Duke University
- 205 shared
R. Blake Billmyre
Stowers Institute for Medical Research
- 202 shared
Soo Chan Lee
Texas Center for Infectious Disease
- 183 shared
Shelby Priest
Duke University Hospital
Education
- 1984
Ph.D., Molecular Biology
Stanford University
- 1979
B.S., Microbiology
University of California, Berkeley
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