Faculty and Research

Joseph Heitman, MD, PhD
James B. Duke Professor
bio  •  lab members  •  lab website

Representative Publications:

  • Alspaugh, J.A., Perfect, J.R., and Heitman, J. (1997) Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunits GPA1 and cAMP. Genes and Development, 11:3206-3217.
  • Dolinski, K., Muir, S., Cardenas, M., and Heitman, J. (1997). All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA., 94:13093-13098.
  • Lorenz, M.C. and Heitman, J. (1997). Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. EMBO Journal, 16:7008-7018.
  • Odom, A., Muir, R.S., Lim, E., Toffaletti, D., Perfect, J., and Heitman, J. (1997). Calcineurin is required for virulence of Cryptococcus neoformans. EMBO Journal, 16:2576-2589.
  • Lorenz, M.C. Heitman, J. (1998). The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO Journal, 17:1236-1247.
  • Pan, X., Heitman, J. (1999). cAMP dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Molecular and Cellular Biology, 19:4874-4887.
  • Lorenz, M.C.*, Pan, X.*, Harashima, T.*, Cardenas, M.E., Xue, Y., Hirsch, J.P., and Heitman, J. (2000). The G-protein coupled receptor Gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics, 154:609-622.
  • Lengeler, K.B., Wang, P., Cox, G.M., Perfect, J.R., and Heitman, J. (2000). Identification of the MATa mating-type locus of Cryptococcus neoformans reveals a serotype A MATa strain thought to have been extinct.  Proc. Natl. Acad. Sci. USA., 97:14455-14460.
  • Cruz, M.C., Fox, D.S., and Heitman J. (2001). Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans. EMBO J., 20:1020-1032.
  • D'Souza, C., Alspaugh, J.A., Yue, C., Harashima, T., Cox, G.M., Perfect, J.R., and Heitman, J. (2001).  Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol., 21:3179-3191.
  • Cruz, M.C., Goldstein, A., Blankenship, J., Davis, D., Del Poeta, M., Cardenas, M.E., Perfect, J.R., McCusker, J.H., and Heitman, J. (2002).  Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J., 21:546-559.
  • Harashima, T., and Heitman, J. (2002).  The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits. Mol. Cell., 10:163-173.
  • Lengeler, K., Fox, D.S., Fraser, J.A., Allen, A., Forrester, K., Dietrich, F.S., and Heitman, J. (2002).  The mating type locus of Cryptococcus neoformans: A step in the evolution of sex chromosomes. Eukaryotic Cell, 1:704-718.
  • Hull, C.M., Davidson, R.C. and Heitman, J. (2002). Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating type-specific homeodomain protein Sxi1alpha. Genes and Development, 16:3046-3060.
  • Nielsen, K., G. M. Cox, P. Wang, D. L. Toffaletti, J. R. Perfect, and J. Heitman. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect Immun., 71:4831-4841, 2003.
  • Idnurm, A., Reedy, J.L., Nussbaum, J.C., and Heitman, J. Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryotic Cell, 3:420-429, 2004.
  • Fraser, J. A., S. Diezmann, R. L. Subaran, A. Allen, K. B. Lengeler, F. S. Dietrich, and J. Heitman. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms. PLoS Biol., 2:e384, 2004.
  • Kraus, P. R., M. J. Boily, S. S. Giles, J. E. Stajich, A. Allen, G. M. Cox, F. S. Dietrich, J. R. Perfect, and J. Heitman. Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray. Eukaryot Cell., 3:1249-60, 2004.
  • Nichols, C. B., J. A. Fraser, and J. Heitman. PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Mol Biol Cell., 15:4476-89, 2004.
  • Marra, R. E., J. C. Huang, E. Fung, K. Nielsen, J. Heitman, R. Vilgalys, and T. G. Mitchell. A genetic linkage map of Cryptococcus neoformans variety neoformans serotype D (Filobasidiella neoformans). Genetics, 167:619-31, 2004.
  • Arevalo-Rodriguez, M., and J. Heitman. Cyclophilin A is localized to the nucleus and controls meiosis in Saccharomyces cerevisiae. Eukaryot Cell., 4:17-29, 2005.
  • Loftus, B. J., E. Fung, P. Roncaglia, D. Rowley, P. Amedeo, D. Bruno, J. Vamathevan, M. Miranda, I. J. Anderson, J. A. Fraser, J. E. Allen, I. E. Bosdet, M. R. Brent, R. Chiu, T. L. Doering, M. J. Donlin, C. A. D'Souza, D. S. Fox, V. Grinberg, J. Fu, M. Fukushima, B. J. Haas, J. C. Huang, G. Janbon, S. J. Jones, H. L. Koo, M. I. Krzywinski, J. K. Kwon-Chung, K. B. Lengeler, R. Maiti, M. A. Marra, R. E. Marra, C. A. Mathewson, T. G. Mitchell, M. Pertea, F. R. Riggs, S. L. Salzberg, J. E. Schein, A. Shvartsbeyn, H. Shin, M. Shumway, C. A. Specht, B. B. Suh, A. Tenney, T. R. Utterback, B. L. Wickes, J. R. Wortman, N. H. Wye, J. W. Kronstad, J. K. Lodge, J. Heitman, R. W. Davis, C. M. Fraser, and R. W. Hyman. The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science, 2005.
  • Bahn, Y.S., Cox, G.M., Perfect, J.R., and Heitman, J. Carbonic anhydrase and CO(2) sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr Biol., 15:2013-2020, 2005.

  • Harashima, T., Anderson, S., Yates, J.R. III, and Heitman, J.
    The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2. Mol Cell., 22:819-30, 2006.

  • Bahn, Y.S., Kojima, K., Cox, G.M., and Heitman, J. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol Biol Cell., 17:3122-35, 2006.

  • Idnurm, A., Rodriguez-Romero, J., Corrochano, L.M., Sanz, C., Iturriaga, E.A., Eslava, A.P., and Heitman, J. The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism
    and other light responses. Proc Natl Acad Sci U S A., 103:4546-51, 2006.

  • Xue, C., Bahn, Y.S., Cox, G.M., and Heitman, J. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol Biol Cell., 17:667-679, 2006.

  • Lin, X., Huang, J.C., Mitchell, T.G., and Heitman, J. Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATα allele enhances filamentation. PLoS Genet., 2:e187, 2006.

  • Hsueh, Y.P., Idnurm, A., and Heitman, J. Recombination hotspots flank the Cryptococcus mating-type locus: Implications for the evolution of a fungal sex chromosome. PLoS Genet., 2:e184, 2006.

  • Heitman, J. Sexual reproduction and the evolution of microbial pathogens. Curr Biol., 16:R711-25, 2006.

  • Onyewu, C. and Heitman, J. Unique applications of novel antifungal drug combinations. Anti-infective Agents in Medicinal Chemistry, 6:3-15, 2007. [Free Open Access]

  • Steinbach, W.J., Reedy, J.L., Cramer, R.A., Perfect, J.R., and Heitman, J. Harnessing calcineurin as a novel anti-infective against fungal infections. Nature Rev Microbiol., 5:418-430, 2007.

  • Fan, W., Idnurm, A., Breger, J., Mylonakis, E., and Heitman, J. Ecal, a sarco/endoplasmic reticulum Ca2+-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans. Infect Immun., 75:3394-3405, 2007. [Epub 2007 May 14].

  • Nielsen, K. and Heitman, J. Sex and virulence of human pathogenic fungi. Adv Genet., 57:143-173, 2007.

  • Fraser, J.A., Stajich, J.E., Tarcha, E.J., Cole, G.T., Inglis, D.O., Sil, A., and Heitman, J. Evolution of the mating type locus: Insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and posadasii. Eukaryot Cell., 6:622-629., 2007.

  • Hicks, J.K. and Heitman, J. Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade. Eukaryot Cell., 6:413-420, 2007.

  • Bahn, Y.S., Xue, C., Idnurm, A., Rutherford, J.C., Heitman, J., and Cardenas, M.E. Sensing the environment: Lessons from fungi. Nat Rev Microbiol., 5:57-69, 2007.

  • Xue, C., Tada, Y., Dong, X., and Heitman, J. The human fungal pathogen Cryptococcus neoformans can complete its sexual cycle during a pathogenic association with plants. Cell Host and Microbe, 1:263-273, 2007.

  • Nielsen, K., DeObaldia, A.L., and Heitman, J. Cryptococcus neoformans mates on pigeon guano: Implications for the realized ecological niche and globalization. Eukaryot Cell., 6:949-959, 2007.
  • Onyewu, C., Eads, E., Schell, W.A., Perfect, J.R., Ullmann, Y., Kaufman, G., Horwitz, B.A., Berdicevesky, I., and Heitman, J. Targeting the calcineurin pathway enhances ergosterol biosynthesis inhibitors agains Trichophyton mentagrophytes in vitro and in a human skin infection model. Antimicrob Agents Chemother., 51:3743-3746, 2007.

  • Upton, A., Fraser, J.A., Kidd, S.E., Bretz, C., Bartlett, K.H., Heitman, J. and Marr, K.A. First contemporary case of human infection with Cryptococcus gattii in Puget Sound: Evidence for spread of the Vancouver Island outbreak. J Clin Microbiol. 45:3086-3088, 2007.

  • Hseuh, Y.P., Xue, C., and Heitman, J. G protein signaling governing cell fate decisions involves opposing G{alpha} subunits in Cryptococcus neoformans. Mol Biol Cell. 18:3237-3249, 2007.

  • Litvintseva, A.P., Lin, X., Templeton, I., Heitman, J., and Mitchell, T.G. Many globally isolated AD hybrid strains of Cryptococcus neoformans originated in Africa. PLoS Pathogens. 8:e114, 2007.

  • Lin, X., Litvintseva, A.P., Nielsen, K., Patel, S., Floyd, A., Mitchell, T.G., and Heitman, J. alphaADalpha hybrids of Cryptococcus neoformans: Evidence of same-sex mating in nature and hybrid fitness. PLoS Genet. 3:e186, 2007.
  • Idnurm, A., Walton, F.J., Floyd, A. and Heitman, J. Identification of the sex genes in an early diverged fungus. Nature, 451:193-196, 2008.