Faculty and Research

Joseph Heitman, MD, PhD
James B. Duke Professor and Chair
research • biography • lab members • alumni • publications • lab website

Selected Publications:

  • Heitman, J. and Model, P. Site-specific methylases induce the SOS DNA repair response in Escherichia coli. J. of Bacteriology, 169: 3243-3250, 1987.

  • Heitman, J., Zinder, N.D. and Model, P. Repair of the Escherichia coli chromosome after in vivo scission by the EcoRI endonuclease. Proc. Natl. Acad. Sci. USA, 86: 2281-2285, 1989.

  • Heitman, J. and Model, P. Substrate recognition by the EcoRI endonuclease. Proteins: Struc, Func. and Genetics, 7: 185-197, 1990.

  • Heitman, J. and Model, P. Mutants of the EcoRI endonuclease with promiscuous substrate specificity implicate residues involved in substrate recognition. EMBO J., 9: 3369-3378, 1990.

  • Heitman, J., Movva, N.R., Hiestand, P.C., and Hall, M.N. FKBP proline rotamase is a target for the immunosuppressive agent FK506 in Saccharomyces cerevisiae, PNAS, 88:1948-1952, 1991.

  • Heitman, J., Movva, N.R., and Hall, M.N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast, Science, 253:905-909, 1991.

  • Breuder, T., Hemenway, C., Movva, N.R., Cardenas, M.E., and Heitman, J. Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains. PNAS, 91: 5372-5376, 1994.

  • Cardenas, M.E., Hemenway, C., Muir, R.S., Ye, R.R., Fiorentino, D.F. and J. Heitman. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. EMBO J., 13:5 944-957, 1994.

  • Cardenas, M.E., Muir, R.S., Breuder, T., and Heitman, J. Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A. EMBO J., 14: 2772-2783, 1995.

  • Cardenas, M.E., and Heitman, J. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J., 14: 5892-5907, 1995.

  • Alarcon, C.M., Cardenas, M.E., and Heitman, J. Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast. Genes & Development 10: 279-288, 1996.

  • Odom*, A., Muir*,R.S., Lim*, E., Tofalletti, D., Perfect, J., and Heitman, J. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J.,16: 2576-2589, 1997.

  • Dolinski, K., Muir, S., Cardenas, M.E., and Heitman, J. All cyclophilins and FKBPs are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. PNAS, 94: 13093-13098, 1997.

  • Lorenz, M.C., and Heitman, J. Yeast pseudohyphal growth is regulated by GPA2, a G protein α homolog. EMBO J., 16: 7008-7018, 1997.

  • Alspaugh, J.A., Perfect, J.R., and Heitman, J. Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP. Genes & Development, 11:3206-3217, 1997.

  • Lorenz, M.C., and Heitman, J. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J., 17:1236-1247, 1998.

  • Dolinski, K.J, Cardenas, M.E., and Heitman, J. CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90, Mol. Cell. Biol., 18:7344-7352, 1998.

  • Cruz, M.C., Cavallo, L.M., Görlach, J.M., Cox, G., Perfect, J.R., Cardenas, M.E., and Heitman, J. Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans. Mol. Cell. Biol., 19:4101-4112, 1999.

  • Pan, X. and Heitman, J. Cyclic AMP dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol. Cell. Biol., 19:4874-4887, 1999.

  • Cardenas, M.E., Cruz, M.C., Del Poeta, M., Chung, N., Perfect, J.R., and Heitman, J. Antifungal activities of antineoplastic agents: yeast as a model system to study drug action. Clin. Micro. Rev., 12:583-611, 1999.

  • Yue, C., Cavallo, L.M., Alspaugh, J.A., Wang, P., Cox, G.M., Perfect, J.R., and Heitman, J. The STE12α homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. Genetics, 153:1601-1615, 1999.

  • Cardenas, M.E., Cutler, N.S., Lorenz, M.C., Di Como, C.J., and Heitman, J. The TOR signaling cascade regulates gene expression in response to nutrients. Genes & Development, 13:3271-3279, 1999.

  • Lorenz, M.C.*, Pan, X.*, Harashima, T.*, Cardenas, M.E., Xue, Y., Hirsch, J.P., and Heitman, J. The G protein-coupled receptor Gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics, 154:609-622, 2000.

  • Wang, P., Perfect, J.R., and Heitman, J. The G-protein β subunit GPB1 is required for mating and haploid fruiting in Cryptococcus neoformans. Mol. Cell. Biol., 20:352-362, 2000.

  • Cruz, M.C.*, Sia, R.A.*, Olson, M., Cox, G.M., and Heitman, J. Roles of calcineurin in physiology and virulence in serotype D and serotype A strains of Cryptococcus neoformans. Infect. Immun., 68:982-985, 2000.

  • Liu, L., Zeng, M., Hausladen, A., Heitman, J., and Stamler, J.S. Protection from nitrosative stress by yeast flavohemoglobin. PNAS, 97:4672-4676, 2000.

  • Young, L.Y., Lorenz, M.C., and Heitman, J. A STE12 homolog is required for mating but dispensable for filamentation in Candida lusitaniae. Genetics, 155:17-29, 2000.

  • Sia, R.A., Lengeler, K.B., and Heitman, J. Diploid strains of the pathogenic basidiomycete Cryptococcus neoformans are thermally dimorphic. Fungal Genet. Biol., 29:153-163, 2000.

  • Arévalo-Rodríguez, M., Cardenas, M.E., Wu, X., Hanes, S.D. and Heitman, J. Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase. EMBO J., 19:3739-3749, 2000.

  • Wu, X., Wilcox, C.B., Devashayam, G., Hackett, R. L., Arevalo-Rodriguez, M., Cardenas, M.E., Heitman, J., and Hanes, S.D. The mitotic Ess1 (Pin1) prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery, EMBO J., 19:3727-3738, 2000.

  • Görlach, J., Fox, D.S., Cutler, N.S., Cox, G.M., Perfect, J.R. and Heitman, J. Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans. EMBO J., 19:3618-3638, 2000.

  • Pan, X. and Heitman, J. Sok2 regulates yeast pseudohyphal differentiation via a transcription factor cascade that regulates cell-cell adhesion. Mol. Cell. Biol. 22:8364-8372, 2000.

  • Lengeler, K.B., Wang, P., Cox, G.M., Perfect, J.R., and Heitman, J. Identification of the MATa mating-type locus of Cryptococcus neoformans reveals a serotype A MATa strain thought to have been extinct. PNAS, 97:14455-14460, 2000.

  • Davidson, R.C., Moore, T.D.E., Odom, A.R., and Heitman, J. Characterization of the MFα pheromone of the human fungal pathogen Cryptococcus neoformans. Mol. Microbiol., 38:1017-1026, 2000.

  • Lengeler, K.B., Davidson, R.C., D'Souza, C., Shen, W-C., Wang, P., Pan, X., Waugh, M., and Heitman, J. Signal transduction cascades regulating fungal development and virulence. MMBR 64:746-785, 2000.

  • Lengeler, K.B., Cox, G.M., and Heitman, J. Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Infect. Immunity, 69:115-122, 2001.

  • Fox, D.S., Cruz, M.C., Sia, R.A.L., Ke, H., Cox, G.M., Cardenas, M.E., and Heitman, J. Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans. Mol. Microbiol., 39:835-849, 2001.

  • Cruz, M.C., Fox, D.S., and Heitman, J. Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans. EMBO J., 20:1020-1032, 2001.

  • D'Souza, C., Alspaugh, J.A., Yue, C., Harashima, T., Cox, G.M., Perfect, J.R., and Heitman, J. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol. 21:3179-3191, 2001.

  • Liu, L., Hausladen, A., Zeng, M., Que, L., Heitman, J., and Stamler, J.S. A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature, 410:490-494, 2001.

  • Wang, P., Cardenas, M.E., Cox, G.M., Perfect, J.R., and Heitman, J. Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans. EMBO Rep., 2:511-518, 2001.

  • Cruz, M.C., Goldstein, A., Blankenship, J., Del Poeta, M., Perfect, J.R., McCusker, J.H., Bennani, Y.L., Cardenas, M.E., and Heitman, J. Rapamycin and nonimmunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR, AAC 45:3162-3170, 2001.

  • Alspaugh, J.A., Pukkila-Worley, R., Harashima, T., Cavallo, L.M., Funnell, D., Cox, G.M., Perfect, J. R., Kronstad, J., and Heitman, J. Adenylyl cyclase functions downstream of the Gα protein Gpa1 and controls mating and virulence of Cryptococcus neoformans, Eukaryotic Cell, 1:75-84, 2002.

  • Cruz, M.C., Goldstein, A., Blankenship, J., Davis, D., Del Poeta, M., Cardenas, M.E., Perfect, J.R., McCusker, J.H., and Heitman, J. Calcineurin is essential for survival during membrane stress in Candida albicans, EMBO Journal, 21:546-559, 2002.

  • Wang, P.*, Nichols, C.B.*, Lengeler, K.B., Cardenas, M.E., Cox, G.M., Perfect, J.R., and Heitman, J. Mating type specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans, Eukaryotic Cell, 1:257-272, 2002.

  • Pan, X., and Heitman, J. Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation, Mol. Cell. Biol., 22:3981-3993, 2002.

  • Shen, W.-C*, Davidson, R.C.*, Cox, G.M., and Heitman, J. Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans, Eukaryotic Cell, 3:366-377, 2002.

  • Harashima, T. and Heitman, J. The Gα protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gβ subunits, Molecular Cell 10: 163-173, 2002.
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  • Davidson, R.C., Blankenship, J.R., Kraus, P.R., De Jesus-Berrios, M., Hull, C.M., D'Souza, C., Wang, P., and Heitman, J. A PCR-based strategy to generate integrative targeting alleles with large regions of homology, Microbiology, 148:2607-2615, 2002.

  • Schein, J.E., Tangen, K.L., Chiu, R., Shin, H., Lengeler, K.B., MacDonald, W.K., Bosdet, I., Heitman, J., Jones, S.J.M., Marra, M.A., and Kronstad, J.W. Physical maps for sequence analysis of the genomes of serotype A and D strains of the fungal pathogen Cryptococcus neoformans, Genome Research, 12:1445-1453, 2002.

  • Hull, C.M., Davidson, R.C., and Heitman, J. Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating type-specific homeodomain protein Sxilα. Genes & Dev., 16:3046-3060, 2002.

  • Lengeler, K.B., Fox, D.S., Fraser, J.A., Allen, A., Forrester, K., Dietrich, F., and Heitman, J. Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryotic Cell 1:704-718, 2002.

  • Hull, C.M. and Heitman, J. Genetics of Cryptococcus neoformans. Annual Review of Genetics, 36:557-615, 2002.

  • Kraus, P.R., Fox, D.S., Cox, G.M., and Heitman, J. The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function, Molecular Microbiology, 48:1377-1387, 2003.

  • Blankenship, J.R., Wormley, F.L., Boyce, M.K., Schell, W.A., Filler, S.G., Perfect, J.R., and Heitman, J. Calcineurin is essential for Candida albicans survival in serum and virulence, Eukaryotic Cell, 2:422-430, 2003.

  • Davidson, R.C., Nichols, C.B., Cox, G.M., Perfect, J.R., and Heitman, J. A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans. Molecular Microbiology, 49:469-485, 2003.

  • Fox, D.S., Cox, G.M., and Heitman, J. Phospholipid-binding protein Cts1 controls septation and functions coordinately with calcineurin in Cryptococcus neoformans. Eukaryotic Cell, 2:1025-1035, 2003.

  • Fraser, J.A., Subaran, R.L., Nichols, C.B., and Heitman J. Recapitulation of the sexual cycle of the primary fungal pathogen C. neoformans var. gattii: Implications for an outbreak on Vancouver Island. Eukaryotic Cell, 2:1036-1045, 2003.

  • De Jesus-Berrios, M., Liu, L., Nussbaum, J., Cox, G.M., Stamler, J.S., and Heitman, J. Enzymes that counteract nitrosative stress promote fungal virulence. Current Biology, 13:1963-1968, 2003.

  • Litvintseva, A.P., Marra, R., Nielsen, K., Heitman, J, Vilgalys, R., and Mitchell, T.G. Evidence of sexual recombination among isolates of Cryptococcus neoformans serotype A in sub-saharan Africa. Eukaryotic Cell, 2:1162-1168, 2003.

  • Nielsen, K., Cox, G.M., Wang, P., Toffaletti, D.L., Perfect, J.R., and Heitman, J. 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., Diezmann, S., Subaran, R.L., Allen, A., Lengeler, K.B., Dietrich, F.S. and Heitman, J. 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, 3:1249-1260, 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, 307:1321-1324, 2005.

  • Idnurm, A. and Heitman, J. Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol., 3:e95, 2005.

  • Lin, X., Hull, C.M., and Heitman, J. Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature, 434:1017-1021, 2005.

  • Nielsen, K., Marra, R.E., Hagen, F., Boekhout, T., Mitchell, T.G., Cox, G.M, and Heitman, J. Interaction between genetic background and the mating-type locus in Cryptococcus neoformans virulence potential. Genetics, 171:975-983, 2005.

  • Harashima, T. and Heitman, J. Galpha subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae. Mol Biol Cell., 16:4557-4571, 2005.

  • Nielsen, K. Cox, G.M., Litvintseva, A.P., Mylonakis, E., Mallaris, S.D., Benjamin, D.K. Jr., Giles, S.S., Mitchell, T.G., Casadevall, A., Perfect, J.R., and Heitman, J. Cryptococcus neoformans {alpha} strains preferentially disseminate to the central nervous system during coinfection. Infect Immun., 73:4922-4933, 2005.

  • Campbell, L.T., Fraser, J.A., Nichols, C.B., Dietrich, F.S., Carter, D., and Heitman, J. Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity. Eukaryotic Cell, 4:1410-1419, 2005.

  • Campbell, L.T., Currie, B.J., Krockenberger, M., Malik, R., Meyer, W., Heitman, J., and Carter, D. Clonality and recombination in genetically differentiated subgroups of Cryptococcus gatti. Eukaryotic Cell, 4:1403-1409, 2005.

  • Fan, W., Kraus, P.R., Boily, M.J., and Heitman, J. Cryptococcus neoformans gene expression during murine macrophage infection. Eukaryotic Cell, 4:1420-1433, 2005.

  • Fox, D.S. and Heitman, J. Calcineurin-binding protein Cbp1 directs the specificity of calcineurin-dependent hyphal elongation during mating in Cryptococcus neoformans. Eukaryotic Cell, 4:1526-1538, 2005.

  • Idnurm, A., Bahn, Y.S., Nielsen, K., Lin, X., Fraser, J.A., and Heitman, J. Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat Rev Microbiol., 3:753-764, 2005.

  • Blankenship, J.R. and Heitman, J. Calcineurin is required for Candida albicans to survive calcium stress in serum. Infect Immun., 73:5767-5774, 2005.

  • Walton, F.J., Idnurm, A., and Heitman, J. Novel gene functions required for melanization of the human pathogen Cryptoccocus neoformans. Mol Microbiol., 57:1381-1396, 2005.

  • Fraser, J.A., Giles, S.S., Wenink, E.C., Guenes-Boyer, S.G., Wright, J.R., Diezmann, S., Allen, A., Stajich, J.E., Dietrich, F.S., Perfect, J.R., and Heitman, J. Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature, 437:1360-1364, 2005.

  • Bahn Y.S., Cox G.M., Perfect J.R., Heitman J. Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr Biol., 15:2013-20, 2005.

  • Xue C., Bahn Y.S., Cox G.M., Heitman J. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol Biol Cell., 17:667-79, 2006.

  • Idnurm A., Rodriguez-Romero J., Corrochano L.M., Sanz C., Iturriaga E.A., Eslava A.P., 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.

  • 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.

  • 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.
  • 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.

  • 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 Coccidioides 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.

  • Rutherford, J.C., Lin, X., Nielsen, K. and Heitman, J. Amt2 permease is required to induce ammonium-responsive invasive growth and mating in Cryptococcus neoformans. Eukaryot Cell. 7:237-246, 2008.

  • Rutherford, J.C., Chua, G., Hughes, T., Cardenas, M.E. and Heitman, J. A Mep2-dependent transcriptional profile links permease function to gene expression during pseudohyphal growth in Saccharomyces cerevisiae. Mol Biol Cell. 19:3028-3039, 2008.

  • Lin, X., Nielsen, K., Patel, S. and Heitman, J. Impact of mating type, serotype, and ploidy on the virulence of Cryptococcus neoformans. Infect Immun. 76:2923-2938, 2008.

  • Bui, T., Lin, X., Malik, R., Heitman, J. and Carter, D. Isolates of Cryptococcus neoformans from infected animals reveal genetic exchange in unisexual, alpha mating type populations. Eukaryot Cell. 7:1771-1780, 2008.

  • Hsueh, Y.P., Fraser, J.A. and Heitman, J. Transitions in sexuality: Recapitulation of an ancestral tri- and tetrapolar mating system in Cryptococcus neoformans. Eukaryot Cell. 7:1847-1855, 2008.

  • Xue, C., Hsueh, Y.P., Chen, L. and Heitman, J. The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans. Mol Microbiol. 70:379-395, 2008.

  • Lee, S.C., Corradi, N., Byrnes, E.J. III, Torres-Martinez, S., Dietrich, F.S., Keeling, P.J. and Heitman, J. Microsporidia evolved from ancestral sexual fungi. Curr Biol. 18:1675-1679, 2008.

  • Findley, K., Rodriguez-Carres, M., Metin, B., Kroiss, J., Fonseca, A., Vilgalys, R., and Heitman, J. Phylogeny and phenotypic characterization of Cryptococcusspecies and closely related saprobic taxa in the Tremellales. Eukaryotic Cell, 8:353-361, 2009.

  • Bastidas, R.J., Heitman, J., and Cardenas, M.E. The protein kinase Tor1 regulates adhesin expression in Candida albicans. PLoS Pathogens, e1000294, 2009.

  • Lin, X., Patel, S., Litvintseva, A.P., Floyd, A., Mitchell, T.G., and Heitman, J. Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating. PLoS Pathogens, e1000283, 2009.

  • Byrnes, E.J., Bildfell, R., Frank, S., Mitchell, T.G., Marr, K., and Heitman, J. Molecular evidence that the Vancouver Island C. gattii outbreak has expanded into the United States Pacific Northwest. Journal of Infectious Diseases, 99:1081-1086, 2009.

  • Shapiro, R.S., Uppuluri, P., Zaas, A.K., Collins, C., Senn, H., Perfect, J.R., Heitman, J., and Cowen, L.E. Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol. 19:621-629, 2009.

  • Hsueh, Y.P., Xue, C., and Heitman, J. A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans. EMBO J. 28:1220-1233, 2009.

  • Sanz, C., Rodriguez-Romero, J., Idnurm, A., Christie, J.M., Heitman, J., Corrochano, L.M., and Eslava, A.P. Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism. Proc Natl Acad Sci USA. 106:7095-7100, 2009.

  • Reedy, J.L., Floyd, A.M., and Heitman, J. Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex. Curr Biol. 19:891-899, 2009.

  • Geunes-Boyer, S., Oliver, T.N., Janbon, G., Lodge, J.K., Heitman, J., Perfect, J.R., and Wright, J.R. Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. Infect Immun. 77:2783-2794, 2009.

  • Butler et al, Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657-662, 2009.

  • Velagapudi, R., Hsueh, Y.P., Geunes-Boyer, S., Wright, J.R., and Heitman, J. Spores as infectious propagules of Cryptococcus neoformans. Infect Immun. 77:4345-4355, 2009.

  • Li, W., Metin, B., White, T.C., and Heitman, J. Organization and evolutionary trajectory of the mating type (MAT) locus in dermatophyte and dimorphic fungal pathogens. Eukaryot Cell. 9:46-58, 2010.

  • Kozubowski, L. and Heitman, J. Septins enforce morphogenetic events during sexual reproduction and contribute to virulence of Cryptococcus neoformans. Mol Microbiol. 75:658-675, 2010.

  • Byrnes, E.J. III, Li, W., Lewit, Y., Ma, H., Voelz, K., Ren, P., Carter, D.A., Chaturvedi, V., Bildfell, R.J., May, R.C., and Heitman, J. Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathogens. 6:e1000850, 2010.

  • Lee, S.C., Corradi, N., Doan, S., Dietrich, F.S., Keeling, P.J., and Heitman, J. Evolution of the sex-related locus and genomic features shared in microsporidia and fungi. PLoS One. 5:e10539, 2010.

  • Lin, X., Jackson, J.C., Feretzaki, M., Xue, C., and Heitman, J. Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans. PLoS Genetics. 6:e1000953, 2010.

  • Metin, B., Findley, K., and Heitman, J. The mating type locus (MAT) and sexual reproduction of Cryptococcus heveanensis: Insights into the evolution of sex and sex-determining chromosomal regions in fungi. PLoS Genetics. 6:e1000961, 2010.

  • Lee, S.C., Ni, M., Li, W., Shertz, C., and Heitman, J. The evolution of sex: A perspective from the fungal kingdom. Microbiology and Molecular Biology Reviews. 74:298-340, 2010.

  • Heitman, J. Evolution of eukaryotic microbial pathoens via covert sexual reproduction. Cell Host Microbe. 8:86-99, 2010.

  • Okagaki, L.H., Strain, A.K., Neilsen, J.N., Charlier, C., Baltes, N.J., Chretien, F. Heitman, J., Dromer, F., and Nielsen, K. Cryptococcal cell morphology affect host cell interactions and pathogenicity. PLoS Pathog. 6:e1000953, 2010.

  • Xue, C., Liu, T., Chen, L., Li, W., Liu, I., Kronstad, J.W., Seyfang, A., and Heitman, J. Role of an expanded inositol transporter repertoire in Cryptococcus neoformans sexual reproduction and virulence. MBio. 1:e00084-10, 2010.

  • Wang, X., Hsueh, Y.P., Li, W., Floyd, A., Skalsky, R., and Heitman, J. Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Genes Dev. 24:2566-2582, 2010. [Abstract] [PDF@Journal]

  • Gryganskyi, A.P., Lee, S.C., Litvintseva, A.P., Smith, M.E., Bonito, G., Porter, T.M., Anishchenko, I.M., Heitman, J., and Vilgalys, R. Structure, function, and phylogeny of the mating locus in the Rhizopus oryzae complex. PLoS One. 5:e15273, 2010. [Abstract] [PDF@Journal]

  • D'Souza, C.A., Kronstad, J.W., Taylor, G., Warren, R., Yuen, M., Hu, G., Jung, W.H., Sham, A., Kidd, S.E., Tangen, K., Lee, N., Zeilmaker, T., Sawkins, J., McVicker, G., Shah, S., Gnerre, S., Griggs, A., Zeng, Q., Bartlett, K., Li, W., Wang, X., Heitman, J., Stajich, J.E., Fraser, J.A., Meyer, W., Carter, D., Schein, J., Krzywinski, M., Kwon-Chung, K.J., Varma, A., Wang, J., Brunham, R., Fyfe, M., Ouellette, B.F., Siddiqui, A., Marra, M., Jones, S., Holt, R., Birren, B.W., Galagan, J.E., Cuomo, C.A. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. MBio. 2:e00342-10, 2011. [Abstract] [PDF@Journal]

  • Chen, Y.L., Brand, A., Morrison, E.L., Silao, F.G., Bigol, U.G., Malbas, F.F. Jr., Nett, J.E., Andes, D.R., Solis, N.V., Filler, S.G., Averette, A., and Heitman, J. Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryot Cell. 10:803-819, 2011. [Epub 2011 Apr 29]. [Abstract] [PDF@Journal]

  • Li, C.H., Cervantes, M., Springer, D.J., Boekhout, T., Ruiz-Vazquez, R.M., Torres-Martinez, S.R., Heitman, J., and Lee, S.C. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides. PLoS Pathog. 7:e1002086, 2011. [Epub 2011 Jun 16]. [Abstract] [PDF@Journal]

  • Kozubowski, L., Aboobakar, E.F., Cardenas, M.E., and Heitman, J. Calcineurin co-localizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans. Eukaryot Cell. 10:1396-1402, 2011. [Abstract] [PDF@Journal]

  • Byrnes, E.J., Li, W., Ren, P., Lewit, Y., Voelz, K., Fraser, J.A., Dietrich, F.S., May, R.C., Chaturvedi, S., Chaturvedi, V., and Heitman, J. A diverse population of Cryptococcus gattii molecular type VGIII in southern Californian HIV/AIDS patients. PLoS Pathogens 7:e1002205, 2011. [Abstract] [PDF@Journal]

  • Ni, M., Feretzaki, M., Sun, S., Wang, X., and Heitman, J. Sex in fungi. Annu Rev Genet 45:405-430, 2011. [Abstract] [PDF@Journal]

  • Aboobakar, E.F., Wang, X., Heitman, J., and Kozubowski, L. The C2 domain protein Cts1 functions in the calcineurin signaling circuit during high-temperature stress responses in Cryptococcus neoformans. Eukaryotic Cell 10:1714-1723, 2011. [Abstract] [PDF@Journal]

  • Semighini, C.P., Averette, A.F., Perfect, J.R., and Heitman, J. Deletion of Cryptococcus neoformans AIF ortholog promotes chromosome aneuploidy and fluconazole-resistance in a metacaspase-independent manner. PLoS Pathogens 7:e1002364, 2011. [Abstract] [PDF@Journal]

  • Bastidas, R.J., Shertz, C.A., Lee, S.C., Heitman, J., and Cardenas, M.E. Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor. Eukaryotic Cell 2011 Dec 30 [Epub ahead of print] [Abstract]
  • Findley, K., Sun, S., Fraser, J.A., Hsueh, Y.P., Averette, A.F., Li, W., Dietrich, F.S., and Heitman, J.  Discovery of a modified tetrapolar sexual cycle in Cryptococcus amylolentus and the evolution of MAT in the Cryptococcus species complex. PLOS Genetics 8:e1002528, 2012. [Abstract] [PDF@Journal]

  • Wang, X., Wang, P., Sun, S., Darwiche, S., Idnurm, A., and Heitman, J.  Mitotic transgene silencing in Cryptococcus neoformans. PLOS Genetics 8:e1002885, 2012. [Abstract] [PDF@Journal]

  • Sun, S., Hsueh, Y.P., and Heitman, J. Gene conversion occurs within the mating-type locus of Cryptococcus neoformans during sexual reproduction. PLOS Genetics 8:e1002810, 2012. [Abstract] [PDF@Journal]

  • Floudas et al. The Paleozoic origin of enzymatic lignin decomposition reconstructed from 31 fungal genome. Science 336:1715-1719, 2012. [Abstract] [PDF@Journal]

  • Martinez et al. Comparative genomic analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection. mBio 3:e00259-12, 2012. [Abstract] [PDF@Journal]

  • Lee, S.C., Phadke, S., Sun, S., and Heitman, J. Pseudohyphal growth of Cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires the Amt1/2 ammonium permeases. Eukaryotic Cell 11:1391-1398, 2012. [Abstract] [PDF@Journal]

  • Li*, W., Sullivan*,T.D., Walton, E., Averette, A.F., Sakthikumar, S., Cuomo, C.A., Klein, B.S., and Heitman, J. Identification of the mating type (MAT) locus that controls sexual reproduction of Blastomyces dermatitidis, Eukaryotic Cell [Epub 9 Nov 2012]. [Abstract] [PDF@Journal]

  • Heitman, J., Sun, S., and James, T.Y. Evolution of fungal sexual reproduction. Mycologia [Epub 25 Oct 2012] in press January 2013. [Abstract] [PDF@Journal]

  • Feretzaki, M., and Heitman, J. Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans. PLoS Genet. 9(8):e1003688, 2013. [Abstract] [PDF@Journal]

  • Lee, S.C., Li, A., Calo, S., and Heitman, J. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides. PLoS Pathog. 9(9):e1003625, 2013. [Abstract] [PDF@Journal]

  • Voelz, K., Ma, H., Phadke, S., Byrnes, E.J., Zhu, P., Mueller, O., Farrer, R.A., Henk, D.A., Lewit, Y., Hsueh, Y.P., Fisher, M.C., Idnurm, A., Heitman, J., and May, R.C. Transmission of hypervirulence traits via sexual reproduction within and between lineages of the human fungal pathogen Cryptococcus gattii. PLoS Genet. 9(9):e1003771, 2013. [Abstract] [PDF@Journal]

  • Ni, M., Feretzaki, M, Li, W., Floyd-Averette, A., Mieczkowski, P., Dietrich, F.S., and Heitman, J. Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans. PLoS Biol. Sep;11(9):e1001653, 2013. [Abstract] [PDF@Journal]

  • Feretzaki, M. and Heitman, J. Unisexual reproduction drives evolution of eukaryotic microbial pathogens. PLoS Pathog. Oct;9(10):e1003674, 2013. [Abstract] [PDF@Journal]