JOSEPH B HEITMAN

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. pmc Light controls growth and development via a conserved pathway in the fungal kingdom
    Alexander Idnurm
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, USA
    PLoS Biol 3:e95. 2005
  2. pmc Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms
    James A Fraser
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
    PLoS Biol 2:e384. 2004
  3. pmc Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi
    Anke Burmester
    Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, Beutenbergstrasse 11a, Jena, 07745, Germany
    Genome Biol 12:R7. 2011
  4. pmc Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom
    Cecelia A Shertz
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    BMC Genomics 11:510. 2010
  5. pmc Is sex necessary?
    Sheng Sun
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    BMC Biol 9:56. 2011
  6. pmc Sex in fungi
    Min Ni
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Genet 45:405-30. 2011
  7. ncbi request reprint The Cryptococcus neoformans genome sequencing project
    J Heitman
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center Durham, NC 27710, USA
    Mycopathologia 148:1-7. 1999
  8. ncbi request reprint Sexual reproduction between partners of the same mating type in Cryptococcus neoformans
    Xiaorong Lin
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 434:1017-21. 2005
  9. pmc Evolution of eukaryotic microbial pathogens via covert sexual reproduction
    Joseph Heitman
    Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710, USA
    Cell Host Microbe 8:86-99. 2010
  10. ncbi request reprint On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans
    J Heitman
    Pharmacology, Howard Hughes Medical Institute, Durham, North Carolina, 27710, USA
    Fungal Genet Biol 28:1-5. 1999

Research Grants

Collaborators

Detail Information

Publications72

  1. pmc Light controls growth and development via a conserved pathway in the fungal kingdom
    Alexander Idnurm
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, USA
    PLoS Biol 3:e95. 2005
    ..These results demonstrate that a role for blue/UV light in controlling development is an ancient process that predates the divergence of the fungi into the ascomycete and basidiomycete phyla...
  2. pmc Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms
    James A Fraser
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
    PLoS Biol 2:e384. 2004
    ..These events resemble those that shaped mammalian sex chromosomes, illustrating convergent evolution in sex-determining structures in the animal and fungal kingdoms...
  3. pmc Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi
    Anke Burmester
    Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, Beutenbergstrasse 11a, Jena, 07745, Germany
    Genome Biol 12:R7. 2011
    ....
  4. pmc Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom
    Cecelia A Shertz
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    BMC Genomics 11:510. 2010
    ....
  5. pmc Is sex necessary?
    Sheng Sun
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    BMC Biol 9:56. 2011
    ..However, presumed asexual species may also be cryptically sexual, as revealed by other recent studies...
  6. pmc Sex in fungi
    Min Ni
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Genet 45:405-30. 2011
    ..As robust and diverse genetic models, fungi provide insights into the molecular nature of sex, sexual specification, and evolution to advance our understanding of sexual reproduction and its impact throughout the eukaryotic tree of life...
  7. ncbi request reprint The Cryptococcus neoformans genome sequencing project
    J Heitman
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center Durham, NC 27710, USA
    Mycopathologia 148:1-7. 1999
    ..neoformans genome sequencing project, and we review here background and arguments for this project. We also discuss the importance of this project to the biology and virulence of this organism in particular, and to virulence in general...
  8. ncbi request reprint Sexual reproduction between partners of the same mating type in Cryptococcus neoformans
    Xiaorong Lin
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 434:1017-21. 2005
    ....
  9. pmc Evolution of eukaryotic microbial pathogens via covert sexual reproduction
    Joseph Heitman
    Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710, USA
    Cell Host Microbe 8:86-99. 2010
    ..Mating-type loci govern fungal sexual identity; how parasites establish sexual identity is unknown. Comparing and contrasting fungal and parasite sex promises to reveal how microbial pathogens evolved and are evolving...
  10. ncbi request reprint On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans
    J Heitman
    Pharmacology, Howard Hughes Medical Institute, Durham, North Carolina, 27710, USA
    Fungal Genet Biol 28:1-5. 1999
    ..Because of the importance of these strains for genetic studies in C. neoformans and the fact that the genomic sequence of one of these strains is in progress, we review here how these congenic strains were originally constructed...
  11. ncbi request reprint Fungal horizons: the Asilomar Fungal Genetics Conference 2007
    Joseph Heitman
    Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, NC 27710, USA
    Fungal Genet Biol 45:77-83. 2008
    ....
  12. ncbi request reprint Sexual reproduction and the evolution of microbial pathogens
    Joseph Heitman
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Curr Biol 16:R711-25. 2006
    ..Continued investigation of the sexual nature of microbial pathogens should facilitate both laboratory investigation and an understanding of the complex interplay between pathogens, hosts, vectors, and their environments...
  13. ncbi request reprint Cell biology. A fungal Achilles' heel
    Joseph Heitman
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Science 309:2175-6. 2005
  14. pmc Calcineurin colocalizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans
    Lukasz Kozubowski
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 10:1396-402. 2011
    ..These results support a model in which calcineurin orchestrates thermal stress responses by associating with sites of mRNA processing...
  15. pmc The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function
    Peter R Kraus
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Microbiol 48:1377-87. 2003
    ..neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall...
  16. pmc Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans
    Julie K Hicks
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 3:14-26. 2004
    ..Our studies illustrate how different components of signaling pathways can be co-opted and functionally specialized during the evolution of related but distinct varieties or subspecies of a human fungal pathogen...
  17. pmc Targeting the calcineurin pathway enhances ergosterol biosynthesis inhibitors against Trichophyton mentagrophytes in vitro and in a human skin infection model
    Chiatogu Onyewu
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Antimicrob Agents Chemother 51:3743-6. 2007
    ..The fluconazole-FK506 combination demonstrated the most obvious advantage over single-drug therapy by clearing conidia and protecting skin from damage at low drug concentrations...
  18. ncbi request reprint Investigation of the basis of virulence in serotype A strains of Cryptococcus neoformans from apparently immunocompetent individuals
    Cletus A D'Souza
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Genet 46:92-102. 2004
    ..Taken together, our findings indicate that the ability of these clinical isolates to infect apparently normal individuals may be attributable to mutations other than pkr1 and/or underlying immune system impairment in patients...
  19. pmc Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms
    Priya Uppuluri
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 52:1127-32. 2008
    ..These findings reveal that calcineurin contributes to fluconazole resistance of biofilms and provide evidence that synergistic drug combinations may prove efficacious as novel therapeutic interventions to treat or prevent biofilms...
  20. pmc Calcineurin is essential for survival during membrane stress in Candida albicans
    M Cristina Cruz
    Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA
    EMBO J 21:546-59. 2002
    ..albicans mutants, against other Candida species, or when combined with different azoles. We propose that calcineurin is part of a membrane stress survival pathway that could be targeted for therapy...
  21. pmc Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence
    Jennifer L Reedy
    Department of Molecular Genetics and Microbiology, Duke University, Box 3546 Research Drive, 322 CARL Bldg, Durham, NC 27710, USA
    Fungal Genet Biol 47:107-16. 2010
    ..These studies extend our understanding of the C. albicans calcineurin signaling cascade and its host-niche specific role in virulence...
  22. pmc Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens
    Jill R Blankenship
    Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    J Clin Microbiol 43:464-7. 2005
    ....
  23. pmc Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes
    Klaus B Lengeler
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University, Durham, North Carolina 27710, USA
    Eukaryot Cell 1:704-18. 2002
    ..Our study establishes a new paradigm for mating-type loci in fungi with implications for the evolution of cell identity and self/nonself recognition...
  24. ncbi request reprint A PCR-based strategy to generate integrative targeting alleles with large regions of homology
    Robert C Davidson
    Department of Molecular Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Microbiology 148:2607-15. 2002
    ..In combination with the availability of the complete genomic sequence, this gene-disruption technique should pave the way for higher throughput genetic analysis of this important pathogenic fungus...
  25. pmc Calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of Aspergillus fumigatus
    Robert A Cramer
    Duke University Medical Center, Box 3499, Pediatric Infectious Diseases, Durham, NC 27710, USA
    Eukaryot Cell 7:1085-97. 2008
    ..In addition, the importance of CrzA to the production of disease is critical, and thus CrzA is an attractive fungus-specific antifungal target for the treatment of invasive aspergillosis...
  26. pmc Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans
    Ping Wang
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 1:257-72. 2002
    ....
  27. pmc Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei
    Chiatogu Onyewu
    Departments of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 47:956-64. 2003
    ....
  28. ncbi request reprint Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs
    Jill R Blankenship
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Curr Opin Investig Drugs 4:192-9. 2003
    ..In summary, these highly successful pharmaceutical agents may find an even broader clinical application in combating infectious diseases...
  29. ncbi request reprint A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans
    Robert C Davidson
    Department of Molecular Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Mol Microbiol 49:469-85. 2003
    ..Our studies illustrate how MAP kinase cascades can be constructed from cell type-specific and non-specific components, yielding pathways that contribute to cell type-specific patterns of signalling and differentiation...
  30. pmc Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae
    Laura Y Young
    Departments of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 47:2717-24. 2003
    ..Our findings reveal that mutation or altered expression of ergosterol biosynthetic genes can result in resistance to amphotericin B in C. lusitaniae...
  31. pmc Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating
    Xiaorong Lin
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS Pathog 5:e1000283. 2009
    ..Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens...
  32. pmc Impact of mating type, serotype, and ploidy on the virulence of Cryptococcus neoformans
    Xiaorong Lin
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Infect Immun 76:2923-38. 2008
    ..This study provides insights into the impact of ploidy, mating type, and serotype on virulence and the impact of hybridization on the fitness and virulence of a eukaryotic microbial pathogen...
  33. pmc The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans
    Chaoyang Xue
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Microbiol 70:379-95. 2008
    ..We conclude that Crg2 participates in controlling both Gpa1-cAMP-virulence and pheromone-mating signalling cascades and hypothesize it may serve as a molecular interface between these two central signalling conduits...
  34. pmc Surfactant protein D binding to Aspergillus fumigatus hyphae is calcineurin-sensitive
    Scarlett Geunes-Boyer
    Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Med Mycol 48:580-8. 2010
    ..Elucidation of the interaction between lung innate immune factors and A. fumigatus could lead to the development of novel therapeutic interventions...
  35. pmc Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex
    Jennifer L Reedy
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Biol 19:891-9. 2009
    ....
  36. pmc Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade
    Read Pukkila-Worley
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 4:190-201. 2005
    ..These studies provide mechanistic insights into the regulation of capsule and melanin production by the C. neoformans cAMP pathway and demonstrate that multiple laccases contribute to C. neoformans melanin production and pathogenesis...
  37. ncbi request reprint Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans
    Kaihei Kojima
    Department of Molecular Genetics and Microbiology, Durham, NC 27710, USA
    Microbiology 152:591-604. 2006
    ..These studies provide evidence that the broad-spectrum antifungal drug fludioxonil exerts its action via activation of the Hog1 MAPK pathway and provide insight into novel targets for synergistic antifungal drug combinations...
  38. pmc The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans
    Chiatogu Onyewu
    Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Research Drive, Duke University Medical Center, Durham, NC 27710, USA
    Infect Immun 72:7330-3. 2004
    ..Crz1 is a proposed downstream target of calcineurin based on studies of Saccharomyces cerevisiae. However, the in vitro phenotypes of C. albicans crz1/crz1 and calcineurin mutants differ and Crz1 is not required for virulence...
  39. ncbi request reprint Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak
    James A Fraser
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 437:1360-4. 2005
    ..This has implications for the emergence of other microbial pathogens and inbreeding in host range expansion in the fungal and other kingdoms...
  40. pmc Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates
    Kirsten Nielsen
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Infect Immun 71:4831-41. 2003
    ..Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence...
  41. pmc Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans
    Wei Chiang Shen
    Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 1:366-77. 2002
    ..neoformans but does contribute to the overall virulence composite. These studies define paracrine and autocrine pheromone response pathways that signal mating and differentiation of this pathogenic fungus...
  42. ncbi request reprint Coping with stress: calmodulin and calcineurin in model and pathogenic fungi
    Peter R Kraus
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Biochem Biophys Res Commun 311:1151-7. 2003
    ....
  43. pmc The alpha-specific cell identity factor Sxi1alpha is not required for virulence of Cryptococcus neoformans
    Christina M Hull
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Infect Immun 72:3643-5. 2004
    ..Experiments have shown that in some backgrounds alpha strains are more virulent than a strains. Our studies reveal that the only known alpha-specific factor, SXI1alpha, is not necessary for virulence...
  44. pmc Phylogeny and phenotypic characterization of pathogenic Cryptococcus species and closely related saprobic taxa in the Tremellales
    Keisha Findley
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 8:353-61. 2009
    ....
  45. doi request reprint Identification of the sex genes in an early diverged fungus
    Alexander Idnurm
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 451:193-6. 2008
    ....
  46. pmc Amt2 permease is required to induce ammonium-responsive invasive growth and mating in Cryptococcus neoformans
    Julian C Rutherford
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham NC 27710, USA
    Eukaryot Cell 7:237-46. 2008
    ..We propose that Amt2 may be a new fungal ammonium sensor and an element of the signaling cascades that govern the mating of C. neoformans in response to environmental nutritional cues...
  47. pmc Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients
    Jennifer L Reedy
    Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Antimicrob Agents Chemother 50:1573-7. 2006
    ..We were unable to detect a difference in susceptibility to calcineurin inhibitors in combination with fluconazole, serum, or calcium in these isolates...
  48. pmc A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans
    Yong Sun Bahn
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Biol Cell 17:3122-35. 2006
    ..Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen...
  49. pmc Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome
    Yen Ping Hsueh
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS Genet 2:e184. 2006
    ..Our findings suggest that during meiosis the MAT locus may be exchanged onto different genetic backgrounds and therefore have broad evolutionary implications with respect to mating-type switching in both model and pathogenic yeasts...
  50. pmc alpha AD alpha hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness
    Xiaorong Lin
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA
    PLoS Genet 3:1975-90. 2007
    ..These findings provide insights on the origins, genetic mechanisms, and fitness impact of unisexual hybridization in the Cryptococcus population...
  51. pmc Calcineurin promotes infection of the cornea by Candida albicans and can be targeted to enhance fluconazole therapy
    Chiatogu Onyewu
    Department of Ophthalmology, Wadsworth Bldg, Box 3802, Erwin Road, Duke University Eye Center, Durham, NC 27710, USA
    Antimicrob Agents Chemother 50:3963-5. 2006
    ..albicans infection more rapidly than monotherapy with either drug. Calcineurin, the target of CsA, was also found to contribute to pathogenicity...
  52. pmc In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus
    William J Steinbach
    Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 48:1664-9. 2004
    ..Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and existing antifungal agents to augment activity against A. fumigatus...
  53. pmc Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa
    Anastasia P Litvintseva
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 2:1162-8. 2003
    ..Our findings provide evidence for sexual recombination among some populations of C. neoformans serotype A from sub-Saharan Africa, which may have a direct impact on their evolution...
  54. pmc Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus
    William J Steinbach
    Department of Pediatrics, Division of Pediatric Infectious Diseases, Box 3499, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 5:1091-103. 2006
    ..Our findings reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention...
  55. pmc Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi
    Xuying Wang
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Genes Dev 24:2566-82. 2010
    ..We hypothesize that the SIS RNAi pathway operates to defend the genome during sexual development...
  56. pmc Structure, function, and phylogeny of the mating locus in the Rhizopus oryzae complex
    Andrii P Gryganskyi
    Department of Biology, Duke University, Durham, North Carolina, United States of America
    PLoS ONE 5:e15273. 2010
    ..oryzae produced sterile zygospores. In spite of the reluctance of most strains to mate in vitro, the conserved sex locus structure and evidence for outcrossing suggest that a normal sexual cycle occurs in both species...
  57. pmc Conserved elements of the RAM signaling pathway establish cell polarity in the basidiomycete Cryptococcus neoformans in a divergent fashion from other fungi
    Felicia J Walton
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Biol Cell 17:3768-80. 2006
    ..neoformans but not in S. cerevisiae. These results indicate that conserved signaling pathways serve both similar and divergent cellular roles in morphogenesis in these divergent organisms...
  58. ncbi request reprint Genetics of Cryptococcus neoformans
    Christina M Hull
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Genet 36:557-615. 2002
    ..These advances have catapulted C. neoformans to center stage as a model of both fungal pathogenesis and the interesting approaches to life that the kingdom of fungi has adopted...
  59. pmc PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans
    Connie B Nichols
    Department of Molecular Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Biol Cell 15:4476-89. 2004
    ..In conclusion, our studies demonstrate that PAK kinases are necessary for polar growth during mating and that polarity establishment is necessary for mating and may contribute to virulence of C. neoformans...
  60. pmc First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen
    Edmond J Byrnes
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
    PLoS ONE 4:e5851. 2009
    ..gattii VGI was transferred from Australia to California, possibly though an association with its common host plant E. camaldulensis, and the patient was exposed in San Francisco and returned to present with disease in North Carolina...
  61. ncbi request reprint Deciphering the model pathogenic fungus Cryptococcus neoformans
    Alexander Idnurm
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Rev Microbiol 3:753-64. 2005
    ..We discuss the biology of C. neoformans in light of this genomic data, with a special emphasis on the role that evolution and sexual reproduction have in the complex relationships of the fungus with the environment and the host...
  62. pmc Cryptococcus neoformans gene expression during murine macrophage infection
    Weihua Fan
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 4:1420-33. 2005
    ..In summary, this gene expression profile allows us to interpret the adaptation of C. neoformans to the intracellular infection process and informs the search for genes encoding novel virulence attributes...
  63. ncbi request reprint Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections
    William J Steinbach
    Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Rev Microbiol 5:418-30. 2007
    ..This Review summarizes our current understanding of calcineurin biology in these fungal species, and its exciting potential role in treating invasive fungal infections...
  64. pmc Calcium- and calcineurin-independent roles for calmodulin in Cryptococcus neoformans morphogenesis and high-temperature growth
    Peter R Kraus
    Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Research Drive, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 4:1079-87. 2005
    ..Our findings reveal that calmodulin performs Ca2+- and calcineurin-independent and -dependent roles in controlling C. neoformans morphogenesis and high-temperature growth...
  65. pmc Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus
    William J Steinbach
    Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA
    Antimicrob Agents Chemother 51:2979-81. 2007
    ..Quantification of 1,3-beta-d-glucan revealed decreased amounts in the calcineurin A (DeltacnaA) mutant. Calcineurin can be an excellent adjunct therapeutic target in combination with other cell wall inhibitors against A. fumigatus...
  66. pmc FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation
    Miguel Arevalo-Rodriguez
    Department of Molecular Genetics and Microbiology, Box 3546, 322 CARL Building, Research Dr, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 3:1287-96. 2004
    ..Because this pathway is conserved in fungi but not in mammals, our findings suggest a facile route to synergistic antifungal drug development via concomitant inhibition of FKBP12 and Hom6...
  67. pmc Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray
    Peter R Kraus
    Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Research Dr, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 3:1249-60. 2004
    ..Our findings demonstrate the utility of even partial-genome microarrays for delineating regulatory cascades that contribute to microbial pathogenesis...
  68. pmc Aspergillus fumigatus calcipressin CbpA is involved in hyphal growth and calcium homeostasis
    Nadthanan Pinchai
    Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 8:511-9. 2009
    ..fumigatus and provides evidence that CbpA may serve as a feedback inhibitor in some aspects of calcineurin functions...
  69. ncbi request reprint Prolyl isomerases in yeast
    Miguel Arevalo-Rodriguez
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Front Biosci 9:2420-46. 2004
    ..Here we review the current state of knowledge about prolyl-isomerases in this model organism...
  70. pmc Organization and evolutionary trajectory of the mating type (MAT) locus in dermatophyte and dimorphic fungal pathogens
    Wenjun Li
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 9:46-58. 2010
    ..These studies further support a foundation to develop molecular and genetic tools for dermatophyte and dimorphic human fungal pathogens...
  71. pmc Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis
    Ying Lien Chen
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Eukaryot Cell 10:803-19. 2011
    ..That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging C. dubliniensis infections...
  72. pmc The evolution of sex: a perspective from the fungal kingdom
    Soo Chan Lee
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Microbiol Mol Biol Rev 74:298-340. 2010
    ....

Research Grants52

  1. Structure, function, and evolution of the Cryptococcus MAT locus
    Joseph Heitman; Fiscal Year: 2009
    ..In particular, the role of genes encoding cell-cell communication molecules involved in the infectious process will be a focus. ..
  2. Novel Antifungal Therapeutic Approaches
    Joseph Heitman; Fiscal Year: 2010
    ..The goal is to harness signaling cascades to develop novel antifungal therapies. ..
  3. Structure, function, and evolution of the Cryptococcus MAT locus
    Joseph Heitman; Fiscal Year: 2011
    ..In particular, the role of genes encoding cell-cell communication molecules involved in the infectious process will be a focus. ..
  4. Genetics Training Grant-Year 26
    Joseph Heitman; Fiscal Year: 2007
    ..Here we seek to expand the NIH supported portion of the training program to a total of eight new students per year. ..
  5. GPCR signaling cascades in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2007
    ....
  6. Genetics of mating and fruiting in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2007
    ..neoformans and C. gattii applicable to development of treatment approaches, diagnostics, or environmental interventions to reduce exposure to infectious spores. ..
  7. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2007
    ..These studies will enable a genome-wide definition of the gene set contributing to virulence of this common human fungal pathogen. ..
  8. Functions of Cryptococcus neoformans mating type loci
    Joseph Heitman; Fiscal Year: 2006
    ..These studies will provide insights into the role of MAT loci and sexual cycles in fungal differentiation and virulence. ..
  9. Role of Calcineurin in Fungal Virulence
    Joseph Heitman; Fiscal Year: 2009
    ..Importantly, this pathway can be targeted for therapeutic intervention using non-immunosuppressive calcineurin inhibitors that retain antifungal activity and synergistic drug combinations that we have discovered. ..
  10. Genetics of mating and fruiting in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2010
    ..neoformans and C. gattii applicable to development of treatment approaches, diagnostics, or environmental interventions to reduce exposure to infectious spores. ..
  11. Structure, function, and evolution of the Cryptococcus MAT locus
    Joseph Heitman; Fiscal Year: 2010
    ..In particular, the role of genes encoding cell-cell communication molecules involved in the infectious process will be a focus. ..
  12. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2009
    ..These studies will enable a genome-wide definition of the gene set contributing to virulence of this common human fungal pathogen. ..
  13. NOVEL ANTIFUNGAL DRUG TARGETS IN CRYPTOCOCCUS NEOFORMANS
    Joseph Heitman; Fiscal Year: 2005
    ..Our long term goal is to identify unique targets and develop novel antifungal drug therapies. ..
  14. ROLE OF CALCINEURIN IN CRYPTOCOCCUS NEOFORMANS VIRULENCE
    Joseph Heitman; Fiscal Year: 2002
    ..Maria Cardenas; biochemical and protein purification support and Dr. John Perfect; transformation of C. neoformans and virulence analysis) combine for a highly enthusiastic rating of this application. ..
  15. IMMUNOSUPPRESSANT TARGETS IN CRYPTOCOCCUS NEOFORMANS
    Joseph Heitman; Fiscal Year: 1999
    ..The Investigator s goals are to identify immunophilins, calcineurin, and their functions in C. neoformans to delineate a signal transduction pathway regulating pathogenesis and to define novel antifungal drug targets. ..
  16. ROLE OF CALCINEURIN IN C. NEOFORMANS MATING AND FRUITING
    Joseph Heitman; Fiscal Year: 2005
    ....