Joseph Heitman
Duke University
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Primary Section: 44, Microbial Biology Secondary Section: 26, Genetics Membership Type:
Member
(elected 2021)
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Biosketch
Joseph Heitman is James B. Duke Professor and Chair, Department of Molecular Genetics and Microbiology, Duke University. Heitman is recognized for fundamental contributions to eukaryotic microbial genetics. With budding yeast, he discovered targets and mechanisms of action for widely-used immunosuppressive/anti-proliferative drugs, defined FKBP12 and TOR as targets of rapamycin, and elucidated TOR-nutrient‐sensing pathways. With pathogenic fungi, he defined mechanisms of infection, drug action and resistance, and sex determination, and discovered unisexual reproduction and how this process drives microbial evolution. Heitman was born in Ohio and grew up in Michigan. He received BS/MS degrees in chemistry/biochemistry, University of Chicago (1984), and MD/PhD degrees from Cornell and Rockefeller Universities (1989/1992). He was an EMBO post-doctoral fellow at the Biozentrum, Basel, Switzerland (1989-1991). In 1992, he joined the Duke University faculty. He was an HHMI Investigator (1992-2005) and Burroughs Wellcome Fund Scholar (1998-2005). He is a member of the National Academy of Sciences, American Academy of Arts and Sciences, Association of American Physicians, American Academy of Microbiology, and the American Society for Clinical Investigation. He received the Gustavo Cudkowicz Prize (1991), ASBMB/AMGEN award (2002), IDSA/Squibb Award (2003), NIH/NIAID MERIT Award (2011-2021), Stanley Korsmeyer Award, ASCI (2018), Rhoda Benham Award, MMSA (2018), ASM Award for Basic Research (2019), and Edward Novitski Prize, Genetics Society of America (2019).
Research Interests
Our research focuses on model and pathogenic fungi addressing fundamental questions of scientific and medical importance in transplantation and infectious diseases. Pioneering studies with Baker’s yeast revealed how immunosuppressive natural products interdict signaling cascades via FKBP12-drug complexes, and discovered TOR as a globally conserved nutrient sensor targeted by the immunosuppressive/antiproliferative drug rapamycin, now widely used in transplantation, cancer chemotherapy, and interventional cardiology. Subsequent studies defined how yeast sense nutrients via ammonium permeases and G‐protein‐coupled receptor‐cAMP cascades in concert with TOR. Our research with pathogenic fungi discovered unisexual reproduction, with implications for pathogen emergence, sex-generated diversity, and origins and evolution of sex. Our lab has developed genetic and genomic approaches elucidating molecular principles of fungal virulence, identifying therapeutic targets, and illustrating convergent evolution of fungal mating-type loci with animal and plant sex chromosomes. Our studies defined the calcium-activated phosphatase calcineurin as a globally conserved fungal virulence factor; structural biology and medicinal chemistry studies are ongoing exploring FK506 analogs as novel antimicrobial therapeutics. Fungal outbreaks afflicting immunocompetent and immunocompromised patients were characterized, revealing responsible lineages, environmental sources, geographic origins, and virulence mechanisms. Our research is further explicating RNAi roles in microbial pathogen genome integrity, hypervirulent outbreak lineages, and drug resistance via epimutation.
