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

• Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen <i>Cryptococcus deneoformans</i>

  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.

  PublisherOA PDFDOI

• Transposon mobilization in the human fungal pathogen <i>Cryptococcus</i> is mutagenic during infection and promotes drug resistance in vitro

  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.

  PublisherOA PDFDOI

• HGT in the human and skin commensal <i>Malassezia</i> : A bacterially derived flavohemoglobin is required for NO resistance and host interaction

  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.

  PublisherOA PDFDOI

• 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.

  DOI

• 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.

  DOI

• Loss of centromere function drives karyotype evolution in closely related Malassezia species

  eLife · 2020 · 74 citations

  • Biology
  • Genetics

  species complex through breakage and inactivation.

  DOI

Recent grants

• NIH Grant R01AI041937

  NIH · $662k · 2001

• Structural Biological Development of Fungal-Specific Calcineurin Inhibitors

  NIH · $669k · 2014–2022

• NIH Grant R01AI042159

  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

• Sheng Sun

  Duke Medical Center

  484 shared

• María E. Cárdenas

  Duke Medical Center

  311 shared

• Anna Floyd Averette

  243 shared

• Vikas Yadav

  Duke University Hospital

  230 shared

• John R. Perfect

  Duke University

  220 shared

• R. Blake Billmyre

  Stowers Institute for Medical Research

  205 shared

• Soo Chan Lee

  Texas Center for Infectious Disease

  202 shared

• Shelby Priest

  Duke University Hospital

  183 shared

Education

• Ph.D., Molecular Biology

  Stanford University

  1984

• B.S., Microbiology

  University of California, Berkeley

  1979

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• Darell Doty Bignerh-190
• Christopher Bang Newgardh-175
• Kun Shan Carolyn Leeh-168