Judith Berman, PhD
Yeast molecular genetics, DNA microarrays for study of Candida albicans, Gene disruption, Fluorescence microscopy of living and fixed cells Immunofluorescence, Green fluorescence protein localization, Fluorescence in situ hybridization
Morphogenesis and pathogenicity in Candida albicans
Candida albicans is the leading cause of invasive fungal disease in premature infants, surgical patients and cancer patients receiving immunosuppressive chemotherapy. Furthermore, despite appropriate anti-fungal therapy, mortality from candidemia is over 30%. While C. albicans is present in the gastrointestinal tracts of virtually all humans, it becomes a pathogen under conditions that permit it to adhere, colonize and invade epithelial tissues. The ability of C. albicans to undergo a morphogenetic switch between a budding yeast form and highly elongated filamentous forms (hyphae and pseudohyphae) is strongly correlated with the virulence of the organism. The lab is investigating the mechanisms of C. albicans morphogenesis. The lab has been analyzing the role of cell cycle regulation and microtubule dynamics in mediating morphogenetic changes in C. albicans. As part of this effort, they have generated yellow, green and cyan-fluorescent protein vectors, adapted for the unique C. albicans codon usage and for selection in C. albicans cells, to follow the localization and movement of proteins within living C. albicans yeast, pseudohyphal and hyphal cells. The Berman lab also studies the role of cytoskeletal proteins, motor proteins and cell cycle checkpoints in morphogenesis and in the cell cycle processes that differ between yeast,pseudohyphae and true hyphae.
Genome instability in Candida albicans
A big problem in the treatment of C. albicans infections is the development of resistance to currently available drugs. We have been investigating the mechanisms by which this occurs and have identified a segmental aneuploidy, generation of two extra copies of the left arm of chromosome 5 in an isochromosome configuration (two identical arms flanking centromere DNA, that is strongly associated with resistance to azole antifungals. We are currently studying the mechanisms by which this isochromosome confers drug resistance as well as the mechanisms and conditions that promote its formation and loss in clinical C. albicans isolates. In addition, these studies have led us to examine the requirements for C. albicans centromere function, as the chromosome 5 centromere is found on isochromosome 5L as well as on the reciprocal product: isochromosome 5R.
Transcriptional rewiring in fungal species
A more recent effort is a collaboration with Dr. Naama Barkai at the Weizmann Institute of Science to study the evolution of genome-wide transcription patterns. We have analyzed, and are currently re-analyzing, all of the available transcription profile data for C. albicans to identify global patterns of gene expression in this organism and to compare those patterns of expression with those of S. cerevisiae and other related yeast species.
Gerami-Nejad, M., Dulmage, K., and J. Berman. 2009. Additional cassettes for epitope and fluorescent fusion proteins in Candida albicans. Yeast, in press.
Butler, G. et al. (~50 authors including Forche and Berman). Evolution of pathogenicity and sexual reproduction revealed by comparing eight Candida genomes. Nature, published online May 24, 2009. doi:10.1038/nature08064.
Forche, A., Magee, P.T., Selmecki, A., Berman, J and G. May. 2009. Genetic and phenotypic variation in Candida albicans increases during passage through a mouse host, Genetics, published online May 2009 doi:10.1534/genetics.109.103325.
Ketel, C., Wang, H.S.W., McClellan, M., Selmecki, A., Gerami-Nejad, M., Bouchonville, K. and J.Berman. Neocentromeres form efficiently at multiple possible loci in Candida albicans. PLoS Genetics, 5 (3): e1000400.
Joglekar, A.P., Bouck, D., Finley, K., Liu, X., Wan, Y., Berman, J., He, X., Salmon, E.D. and K.S. Bloom. 2008. Molecular architecture of kinetochore-microtubule attachment sites is conserved between point and regional centromeres. J. Cell Biol. 121:466-76
Forche, A., Alby, K., Schaefer, D., Johnson, A.D., Berman, J. and R. Bennett. 2008.. The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains. PLoS Biology, 6(5) e110.
Selmecki, A., Gerami-Nejad, M., Paulson, C., Forche, A. and J. Berman. 2008. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol. Microbiol. 68: 624-641.
Finley, K., A. Quick, and J. Berman 2008. Dynein-dependent nuclear dynamics affect morphogenesis in Candida albicans via the Bub2p spindle checkpoint. J Cell Science, 121: 466-476
Legrande, M., Forche, A., Selmecki, A.M., Kirkpatrick, D., Berman, J. 2008. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies. PLoS Genetics, 4(1):e1 0018-0028.
Tirosh, I., Berman, J., and N. Barkai. 2007. Localized DNA rigidity characterizes TATA-less promoters in yeast. Trends Genet.23(7): 318-321
Berman, J. 2006. Morphogenesis and cell cycle progression in Candida albicans Curr. Opin. Microbiol. 9: 595-601.
Selmecki, A., Forche, A., J. Berman. 2006. Aneuploidy and Isochromosome Formation in Drug Resistant Candida albicans. Science, 313:367-370.
Oberholzer, U., Nantel, A., Berman, J., and M. Whiteway. 2006. Transcript profiles of Candida albicans cortical actin patch mutants reflect their cellular defects: contribution of the Hog1p and Mkc1p signaling pathways. . Eukaryot. Cell 5: 1252-1265.
Bergmann, S., Ihmels, J., and J. Berman 2006. Global transcription profiles of C. albicans and the comparison with other yeast species, In Candida: Comparative and Functional Genomics. B. Hube and C. D’enfert, editors.
Coste, A., Turner, V., Ischer, F., Morschhäuser,J., Forche, A., Semelcki, A., Berman,J., Bille,J. and D. Sanglard. 2006. A mutation in Tac1p, a transcription factor regulating CDR1 andCDR2, is coupled with loss of heterozygosity at Chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics, 172: 2139-56.
Ihmels, J. Bergmann, S., Berman, J. and N. Barkai. (2005) The Differential Clustering for comparative gene expression analysis: application to the Candida albicans transcription program. PloS Genetics. 1: e39;0380-0393.
Finley, F. and Berman, J. 2005. Microtubules in C. albicans hyhpae drive nuclear dynamics and connect cell cycle progression to morphogenesis. Eukaryotic Cell, 4 (10): 1697-1711. Featured on the cover of the journal and highlighted in ASM News Nov. 2005.
Ihmels, J., Bergmann, S., Gerami-Nejad, M., Yanai, I., Berman, J. and N. Barkai. (2005) Rewiring of the yeast transcriptional network through the evolution of motif usage. Science. 309:938-40.
Bensen, E.S., Clemente-Blanco, A., Finley, K.R., Correa-Bordes, J., and Berman, J. (2005) The Mitotic Cyclins Clb2p and Clb4p Affect Morphogenesis in Candida albicans. Mol Biol Cell. 16:387-400.
Crampin, H., Finley, K., Gerami-Nejad, M., Court, H., Gale, C., Berman, J. and P. Sudbery. (2005) Candida albicans hyphae have a Spitzenkörper that is a distinct structure from the polarisome found yeast and pseudohyphae. J. Cell Sci. 118:2935-47.
Braun, et al. (#37 out of 43 authors) (2005) A human-curated annotation of the Candida albicans genome. PloS Genetics, 1:36-57.
Selmecki, A., Bergmann, S. and J. Berman (2005) Comparative Genome Hybridization reveals widespread aneuploidy in Candida albicans laboratory strains. Mol. Microbiol. 55:1553-65.
Glowczewski L, Waterborg JH, and J Berman (2004) yeast Chromatin Assembly Complex-1 Protein Excludes Non-Acetylatable histone H4 from Chromatin and the nucleus. Mol. Cell. Biol... 24: 10180-10192.
Bensen E, Martin S, Berman J, and Davis DA (2004) Transcriptional profiling in C. albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. Mol. Microbiol. 54(5): 1335-1351.
Sudbery, P., Gow, N. and J. Berman (2004) The distinct morphogenic states of Candida albicans Trends in Microbiology, in press.
Berman, J. and N.A.R. Gow (2004) Cell cycle in Human fungal Pathogens. In: Pathogenic Fungi: Structural Biology and Taxonomy, SanBlas, G. and R. Calderone, eds., Horizon press Norfolk, UK, Pp. 1001-127.
Gerami-Nejad, M., Berman, J. Galke, C.A. (2004) Cassettes for the PCR-mediated construction of regulatable alleles in C. albicans. yeast, 21:429-436.
Enomot, S., Glowczewski, L., lew-Smith, J. and Berman, J.G. (2004) Telomore cap components influence the rate of senescence in telomerase-dificient yeast cells. Mol. Cell. Bol. 24:837-845.
Tseng-Rogenski, S.S.-I., Chong, J.-L., Thomas, C.B., Enomoto, S., Berman, J. and Chang, T.-H. (2003) Functional conservation for Dhh 1p, a DexD/H-box protein in S. cerevisiae. Nucleic Acids Res. 31:4995-5002.
Enomoto, S., Glowczewski, L., Lew-Smith, J. and Berman, J.G. (2004) Telomore cap components influence the rate of senescence in telomerase-dificient yeast cells. Mol. Cell. Biol.24:837-845.
Gerami-Nejad, M., Berman, J. and Gale, C.A. (2004) Cassettes for the PCR-mediated construction of regulatable alleles in C. albicans. Yeast, 21:429-436.
Dahlseid, J.N., Lew-Smith, J., Lelivelt, M.J., Enomoto, S., Ford, A., Desruisseaux, M., McClellan, M., Lue, N., Culbertson, M.R. and Berman, J. (2003) mRNAs encoding telomerase components and regulators are controlled by the UPF genes in Saccharomyces cerevisiae. Euk. Cell., 2(1): 134-42
Bensen, E.S., Filler, S.G. and Berman, J. (2002) A forkhead transcription factor is important for both yeast and true hyphal growth in Candida albicans, Euk. Cell., 1(5),787-798.
Berman, J. and Sudbery, P.E. (2002) Candida albicans: a molecular revolution built on lessons from Saccharomyces cerevisiae. Nature Reviews Genetics, 3:918-32.
Enomoto, S., Glowczewski, L. and J. Berman. 2002. MEC3, MEC1 and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae.Mol. Biol. of the Cell. 13: 2626-2638
Gale, C., Gerami, M., McClellan, M., Vandonink, S., Longtine, M. & Berman, J. 2001 Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells. Mol. Biol. Cell,. 12:3538-49.
Gerami-Nejad, M., J. Berman, and C. A. Gale. 2001. Cassettes for PCR-mediated construction of green, yellow and cyan fluorescent protein fusions in Candida albicans. Yeast. 18:859-864.
Asleson, C. M., E. S. Bensen, C. A. Gale, A. S. Melms, C. Kurischko, and J. Berman. 2001. Candida albicans INT1-induced filamentation in S. cerevisiae depends on Sla2p. Mol Cell Biol. 21:1272-84.
Johnston, S.D., Enomoto, S., Schneper, L., McClellan, M.C., Twu, F., Montgomery, N.D., Haney, S.A., Broach, J.R. and Berman, J., 2001. CAC3(MSI1) suppression of RAS2(G19V) is independent of chromatin assembly factor I and mediated by NPR1, Mol Cell Biol, 21: 1784-94.
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