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Last Name

David E Levin, PhD

TitleProfessor
InstitutionBoston University Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology
Address75 E. Newton St Evans Building
Boston MA 02118
Phone(617) 414-1057
ORCID ORCID Icon0000-0003-0696-2860
Other Positions
TitleProfessor
InstitutionBoston University School of Medicine
DepartmentMicrobiology

TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine, Graduate Medical Sciences

TitleProfessor of Molecular & Cell Biology
InstitutionBoston University Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology

 Research Expertise & Professional Interests
Expertise in stress signaling and cell wall biogenesis in fungi.

We use baker’s yeast, Saccharomyces cerevisiae, as a model genetic organism in which to study the molecular mechanisms of stress signaling. The biomedical relevance of our work is centered on the identification of potential antifungal drug targets. One project concerns the dissection of the Cell Wall Integrity (CWI) signaling pathway, which detects and responds to cell wall stress during growth and morphogenesis. Because animal cells lack cell walls, this structure is an attractive target in fungal pathogens. Disruption of the fungal cell wall results in cell lysis. The CWI pathway uses a set of cell surface sensors that are connected to a small G-protein (Rho1), which activates signaling through a MAP kinase cascade. We have found in recent studies that the Mpk1 MAP kinase of the CWI pathway has a non-catalytic function in transcription initiation and elongation, in addition to its catalytic activity as a protein kinase. We are now working to understand this novel mechanism for transcriptional regulation.

A second project exploits the need of fungal cells to maintain osmotic homeostasis through the regulation of intracellular glycerol concentration. We have identified a pair of genes, named RGC1 and RGC2 (for Regulators of the Glycerol Channel) whose function is to control the activity of the Fps1 glycerol channel, which acts as a plasma membrane vent that decreases turgor pressure by releasing glycerol from the cell. The fungal kingdom is replete with members of the Rgc family of proteins, but they have not been found in metazoan organisms. For this reason, and because mutants in these genes undergo cell lysis as a result of excess turgor pressure, the Rgc proteins may be suitable antifungal targets. Current studies are centered on understanding the biochemical function of Rgc1/2 and their mode of regulation in response to osmotic stress.

 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Lee J, Reiter W, Dohnal I, Gregori C, Beese-Sims S, Kuchler K, Ammerer G, Levin DE. MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators. Genes Dev. 2013 Dec 1; 27(23):2590-601.
    View in: PubMed
  2. Beese-Sims SE, Pan SJ, Lee J, Hwang-Wong E, Cormack BP, Levin DE. Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress. Eukaryot Cell. 2012 Dec; 11(12):1512-9.
    View in: PubMed
  3. Levin DE. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics. 2011 Dec; 189(4):1145-75.
    View in: PubMed
  4. Beese-Sims SE, Lee J, Levin DE. Yeast Fps1 glycerol facilitator functions as a homotetramer. Yeast. 2011 Dec; 28(12):815-9.
    View in: PubMed
  5. Kim KY, Levin DE. Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination. Cell. 2011 Mar 4; 144(5):745-56.
    View in: PubMed
  6. Kim KY, Levin DE. Transcriptional reporters for genes activated by cell wall stress through a non-catalytic mechanism involving Mpk1 and SBF. Yeast. 2010 Aug; 27(8):541-8.
    View in: PubMed
  7. Kim KY, Truman AW, Caesar S, Schlenstedt G, Levin DE. Yeast Mpk1 cell wall integrity mitogen-activated protein kinase regulates nucleocytoplasmic shuttling of the Swi6 transcriptional regulator. Mol Biol Cell. 2010 May 1; 21(9):1609-19.
    View in: PubMed
  8. Beese SE, Negishi T, Levin DE. Identification of positive regulators of the yeast fps1 glycerol channel. PLoS Genet. 2009 Nov; 5(11):e1000738.
    View in: PubMed
  9. Truman AW, Kim KY, Levin DE. Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation. Mol Cell Biol. 2009 Dec; 29(24):6449-61.
    View in: PubMed
  10. Levin DE, Stamper RJ. The N-actetylglucosamine-PI transfer reaction, the GlcNAc-PI transferase complex, and its regulation. In The Enzymes, Ed.. A. K. Menon, T. Kinoshita, P. Orlean, F. Tamanoi. Academic Press. 2009; 26:31-47.
  11. Kim KY, Truman AW, Levin DE. Yeast Mpk1 mitogen-activated protein kinase activates transcription through Swi4/Swi6 by a noncatalytic mechanism that requires upstream signal. Mol Cell Biol. 2008 Apr; 28(8):2579-89.
    View in: PubMed
  12. Kim KY, Cosano IC, Levin DE, Molina M, Martín H. Dissecting the transcriptional activation function of the cell wall integrity MAP kinase. Yeast. 2007 Apr; 24(4):335-42.
    View in: PubMed
  13. Levin DE. Review of The Edge of Evolution: The Search for the Limits of Darwinism, for Reports of the National Center for Science Education. 2007; 27:38-40.
    View in: External Website
  14. Newman HA, Romeo MJ, Lewis SE, Yan BC, Orlean P, Levin DE. Gpi19, the Saccharomyces cerevisiae homologue of mammalian PIG-P, is a subunit of the initial enzyme for glycosylphosphatidylinositol anchor biosynthesis. Eukaryot Cell. 2005 Nov; 4(11):1801-7.
    View in: PubMed
  15. Levin DE. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 2005 Jun; 69(2):262-91.
    View in: PubMed
  16. Vay HA, Philip B, Levin DE. Mutational analysis of the cytoplasmic domain of the Wsc1 cell wall stress sensor. Microbiology. 2004 Oct; 150(Pt 10):3281-8.
    View in: PubMed
  17. Sobering AK, Watanabe R, Romeo MJ, Yan BC, Specht CA, Orlean P, Riezman H, Levin DE. Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER. Cell. 2004 May 28; 117(5):637-48.
    View in: PubMed
  18. Sobering AK, Romeo MJ, Vay HA, Levin DE. A novel Ras inhibitor, Eri1, engages yeast Ras at the endoplasmic reticulum. Mol Cell Biol. 2003 Jul; 23(14):4983-90.
    View in: PubMed
  19. Romeo MJ, Angus-Hill ML, Sobering AK, Kamada Y, Cairns BR, Levin DE. HTL1 encodes a novel factor that interacts with the RSC chromatin remodeling complex in Saccharomyces cerevisiae. Mol Cell Biol. 2002 Dec; 22(23):8165-74.
    View in: PubMed
  20. Jung US, Sobering AK, Romeo MJ, Levin DE. Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase. Mol Microbiol. 2002 Nov; 46(3):781-9.
    View in: PubMed
  21. Sobering AK, Jung US, Lee KS, Levin DE. Yeast Rpi1 is a putative transcriptional regulator that contributes to preparation for stationary phase. Eukaryot Cell. 2002 Feb; 1(1):56-65.
    View in: PubMed
  22. Berlin V, Levin DE, Ohya Y, Damagnez V, Smith SE. Assays and Reagents for Identifying Anti-Fungal Agents, and Uses Related Thereto. 2001.
  23. Philip B, Levin DE. Wsc1 and Mid2 are cell surface sensors for cell wall integrity signaling that act through Rom2, a guanine nucleotide exchange factor for Rho1. Mol Cell Biol. 2001 Jan; 21(1):271-80.
    View in: PubMed
  24. Jung US, Levin DE. Genome-wide analysis of gene expression regulated by the yeast cell wall integrity signalling pathway. Mol Microbiol. 1999 Dec; 34(5):1049-57.
    View in: PubMed
  25. Rajavel M, Philip B, Buehrer BM, Errede B, Levin DE. Mid2 is a putative sensor for cell integrity signaling in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Jun; 19(6):3969-76.
    View in: PubMed
  26. Zhao C, Jung US, Garrett-Engele P, Roe T, Cyert MS, Levin DE. Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol Cell Biol. 1998 Feb; 18(2):1013-22.
    View in: PubMed
  27. Gray JV, Ogas JP, Kamada Y, Stone M, Levin DE, Herskowitz I. A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator. EMBO J. 1997 Aug 15; 16(16):4924-37.
    View in: PubMed
  28. Kamada Y, Qadota H, Python CP, Anraku Y, Ohya Y, Levin DE. Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem. 1996 Apr 19; 271(16):9193-6.
    View in: PubMed
  29. Qadota H, Python CP, Inoue SB, Arisawa M, Anraku Y, Zheng Y, Watanabe T, Levin DE, Ohya Y. Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3-beta-glucan synthase. Science. 1996 Apr 12; 272(5259):279-81.
    View in: PubMed
  30. Davenport KR, Sohaskey M, Kamada Y, Levin DE, Gustin MC. A second osmosensing signal transduction pathway in yeast. Hypotonic shock activates the PKC1 protein kinase-regulated cell integrity pathway. J Biol Chem. 1995 Dec 15; 270(50):30157-61.
    View in: PubMed
  31. Errede B, Cade RM, Yashar BM, Kamada Y, Levin DE, Irie K, Matsumoto K. Dynamics and organization of MAP kinase signal pathways. Mol Reprod Dev. 1995 Dec; 42(4):477-85.
    View in: PubMed
  32. Kamada Y, Jung US, Piotrowski J, Levin DE. The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Genes Dev. 1995 Jul 1; 9(13):1559-71.
    View in: PubMed
  33. Levin DE, Errede B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol. 1995 Apr; 7(2):197-202.
    View in: PubMed
  34. Johnson DR, Knoll LJ, Levin DE, Gordon JI. Saccharomyces cerevisiae contains four fatty acid activation (FAA) genes: an assessment of their role in regulating protein N-myristoylation and cellular lipid metabolism. J Cell Biol. 1994 Nov; 127(3):751-62.
    View in: PubMed
  35. Levin DE, Stevenson WD, Watanabe M. Evidence against the existence of the purported Saccharomyces cerevisiae PKC2 gene. Curr Biol. 1994 Nov 1; 4(11):990-5.
    View in: PubMed
  36. Simchen G, Chapman KB, Caputo E, Nam K, Riles L, Levin DE, Boeke JD. Mapping of DBR1 and YPK1 suggests a major revision of the genetic map of the left arm of Saccharomyces cerevisiae Chromosome XI. Genetics. 1994 Oct; 138(2):283-7.
    View in: PubMed
  37. Lee KS, Patton JL, Fido M, Hines LK, Kohlwein SD, Paltauf F, Henry SA, Levin DE. The Saccharomyces cerevisiae PLB1 gene encodes a protein required for lysophospholipase and phospholipase B activity. J Biol Chem. 1994 Aug 5; 269(31):19725-30.
    View in: PubMed
  38. Watanabe M, Chen CY, Levin DE. Saccharomyces cerevisiae PKC1 encodes a protein kinase C (PKC) homolog with a substrate specificity similar to that of mammalian PKC. J Biol Chem. 1994 Jun 17; 269(24):16829-36.
    View in: PubMed
  39. Levin DE, Bowers B, Chen CY, Kamada Y, Watanabe M. Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae. Cell Mol Biol Res. 1994; 40(3):229-39.
    View in: PubMed
  40. Lee KS, Hines LK, Levin DE. A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway. Mol Cell Biol. 1993 Sep; 13(9):5843-53.
    View in: PubMed
  41. Lee KS, Irie K, Gotoh Y, Watanabe Y, Araki H, Nishida E, Matsumoto K, Levin DE. A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. Mol Cell Biol. 1993 May; 13(5):3067-75.
    View in: PubMed
  42. Irie K, Takase M, Lee KS, Levin DE, Araki H, Matsumoto K, Oshima Y. MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C. Mol Cell Biol. 1993 May; 13(5):3076-83.
    View in: PubMed
  43. Errede B, Levin DE. A conserved kinase cascade for MAP kinase activation in yeast. Curr Opin Cell Biol. 1993 Apr; 5(2):254-60.
    View in: PubMed
  44. Chen P, Lee KS, Levin DE. A pair of putative protein kinase genes (YPK1 and YPK2) is required for cell growth in Saccharomyces cerevisiae. Mol Gen Genet. 1993 Jan; 236(2-3):443-7.
    View in: PubMed
  45. Levin DE, Bartlett-Heubusch E. Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect. J Cell Biol. 1992 Mar; 116(5):1221-9.
    View in: PubMed
  46. Lee KS, Levin DE. Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog. Mol Cell Biol. 1992 Jan; 12(1):172-82.
    View in: PubMed
  47. Levin DE, Bishop JM. A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1990 Nov; 87(21):8272-6.
    View in: PubMed
  48. Levin DE, Fields FO, Kunisawa R, Bishop JM, Thorner J. A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Cell. 1990 Jul 27; 62(2):213-24.
    View in: PubMed
  49. Levin DE, Hammond CI, Ralston RO, Bishop JM. Two yeast genes that encode unusual protein kinases. Proc Natl Acad Sci U S A. 1987 Sep; 84(17):6035-9.
    View in: PubMed
  50. Hartman PE, Ames BN, Roth JR, Barnes WM, Levin DE. Target sequences for mutagenesis in Salmonella histidine-requiring mutants. Environ Mutagen. 1986; 8(4):631-41.
    View in: PubMed
  51. Levin DE, Ames BN. Classifying mutagens as to their specificity in causing the six possible transitions and transversions: a simple analysis using the Salmonella mutagenicity assay. Environ Mutagen. 1986; 8(1):9-28.
    View in: PubMed
  52. Marnett LJ, Hurd HK, Hollstein MC, Levin DE, Esterbauer H, Ames BN. Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA104. Mutat Res. 1985 Jan-Feb; 148(1-2):25-34.
    View in: PubMed
  53. Levin DE, Marnett LJ, Ames BN. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102. Proc Natl Acad Sci U S A. 1984 Jul; 81(14):4457-61.
    View in: PubMed
  54. Chesis PL, Levin DE, Smith MT, Ernster L, Ames BN. Mutagenicity of quinones: pathways of metabolic activation and detoxification. Proc Natl Acad Sci U S A. 1984 Mar; 81(6):1696-700.
    View in: PubMed
  55. Levin DE, Hollstein M, Christman MF, Ames BN. Detection of oxidative mutagens with a new Salmonella tester strain. Methods in Enzymology. 1984; 105:249-254.
  56. Levin DE, Hollstein M, Christman MF, Ames BN. Detection of oxidative mutagens with a new Salmonella tester strain (TA102). Methods Enzymol. 1984; 105:249-54.
    View in: PubMed
  57. Vance WA, Levin DE. Structural features of nitroaromatics that determine mutagenic activity in Salmonella typhimurium. Environ Mutagen. 1984; 6(6):797-811.
    View in: PubMed
  58. Levin DE, Hollstein M, Christman MF, Schwiers EA, Ames BN. A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci U S A. 1982 Dec; 79(23):7445-9.
    View in: PubMed
  59. Levin DE, Yamasaki E, Ames BN. A new Salmonella tester strain, TA97, for the detection of frameshift mutagens. A run of cytosines as a mutational hot-spot. Mutat Res. 1982 Jun; 94(2):315-30.
    View in: PubMed
  60. Levin DE, Lovely TJ, Klekowski E. Light-enhanced genetic toxicity of crystal violet. Mutat Res. 1982 Mar; 103(3-6):283-8.
    View in: PubMed
  61. Lovely TJ, Levin DE, Klekowski E. Light-induced genetic toxicity of thimerosal and benzalkonium chloride in commercial contact lens solutions. Mutat Res. 1982 Mar; 101(1):11-8.
    View in: PubMed
  62. Levin DE, Blunt EL, Levin RE. Modified fluctuation test for the direct detection of mutagens in foods with Salmonella typhimurium TA98. Mutat Res. 1981 Oct; 85(5):309-21.
    View in: PubMed
  63. Levin DE, Barnes WS, Klekowski E. Mutagenicity of fluorene derivatives: a proposed mechanism. Mutat Res. 1979 Nov; 63(1):1-10.
    View in: PubMed
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