David E Levin, PhD
Professor
Boston University Henry M. Goldman School of Dental Medicine
Dept of Molecular & Cell Biology

PhD, University of California at Berkeley



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 twofold. First, we seek to identify novel aspects of signal transduction that are evolutionarily conserved with humans and therefore tell us something about our own biology that may be useful in the treatment of disease. Second, when we identify aspects or components of signaling pathways that are unique to fungi, these often represent potential targets for antifungal drug discovery.

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 drug 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, which activates signaling through a MAP kinase cascade. We have found in recent studies that, in addition to its catalytic activity as a protein kinase, the MAP kinase of the CWI pathway has a previously unknown non-catalytic function in the control of transcription elongation. We found that the basal expression of many stress-induced genes is minimized through premature transcription termination (or attenuation) shortly after initiation. The non-catalytic function of the MAP kinase under stress conditions is to prevent transcription attenuation through its interaction with the transcription elongation complex. This mechanism appears to be evolutionarily conserved in humans and may offer a new approach to therapeutic gene silencing.

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.

Professor
Boston University School of Medicine
Microbiology


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Division of Graduate Medical Sciences


Professor of Molecular & Cell Biology
Boston University Henry M. Goldman School of Dental Medicine
Molecular & Cell Biology



2006 Faculty of 1000 Biology member (Microbiology)
1996 JHU nominee for HHMI appointment
1994 American Cancer Society: Faculty Research Award
1991 American Cancer Society: Junior Faculty Research Award
1987 American Cancer Society, California Division: Senior Postdoctoral Fellow
1984 Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellow


Intracellular stress Inputs to MAPK Signaling Pathways
01/19/2016 - 12/31/2017 (PI)
NIH/National Institute of General Medica
5R01GM048533-23

Control of Transcriptional Attenuation of Stress-induced Genes in Yeast
07/23/2012 - 04/30/2017 (PI)
NIH/National Institute of General Medica
5R01GM102136-04

Cell Wall Integrity Signaling in Yeast
07/01/2010 - 01/18/2016 (PI)
NIH/National Institute of General Medica
5R01GM048533-21




Yr Title Project-Sub Proj Pubs
2017 Intracellular stress inputs to MAPK signaling pathways 5R01GM048533-23 41
2016 Intracellular stress inputs to MAPK signaling pathways 2R01GM048533-22 41
2015 Control of Transcriptional Attenuation of Stress-induced Genes in Yeast 5R01GM102136-04
2014 Control of Transcriptional Attenuation of Stress-induced Genes in Yeast 5R01GM102136-03
2014 PA-12-149:Diversity Supplement for 5 R01 GM048533-21 3R01GM048533-21S1 41
2014 Cell Wall Integrity Signaling in Yeast 3R01GM048533-21S2 41
2013 Control of Transcriptional Attenuation of Stress-induced Genes in Yeast 5R01GM102136-02
2013 Cell Wall Integrity Signaling in Yeast 5R01GM048533-21 41
2012 Control of Transcriptional Attenuation of Stress-induced Genes in Yeast 1R01GM102136-01
2012 Cell Wall Integrity Signaling in Yeast 5R01GM048533-20 41
Showing 10 of 34 results. Show All Results
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.

  1. Lee J, Levin DE. Rgc2 Regulator of Glycerol Channel Fps1 Functions as a Homo- and Heterodimer with Rgc1. Eukaryot Cell. 2015 Jul; 14(7):719-25. PMID: 26024902; PMCID: PMC4486678; DOI: 10.1128/EC.00073-15;.
  2. 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. PMID: 24298058; PMCID: PMC3861672; DOI: 10.1101/gad.229310.113;.
  3. 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. PMID: 23087370; PMCID: PMC3536289; DOI: 10.1128/EC.00231-12;.
  4. Levin DE. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics. 2011 Dec; 189(4):1145-75. PMID: 22174182; PMCID: PMC3241422; DOI: 10.1534/genetics.111.128264;.
  5. Beese-Sims SE, Lee J, Levin DE. Yeast Fps1 glycerol facilitator functions as a homotetramer. Yeast. 2011 Dec; 28(12):815-9. PMID: 22030956; PMCID: PMC3230664; DOI: 10.1002/yea.1908;.
  6. 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. PMID: 21376235; PMCID: PMC3063357; DOI: 10.1016/j.cell.2011.01.034;.
  7. 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. PMID: 20641022; PMCID: PMC3142540; DOI: 10.1002/yea.1782;.
  8. 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. PMID: 20219973; PMCID: PMC2861618; DOI: 10.1091/mbc.E09-11-0923;.
  9. Beese SE, Negishi T, Levin DE. Identification of positive regulators of the yeast fps1 glycerol channel. PLoS Genet. 2009 Nov; 5(11):e1000738. PMID: 19956799; PMCID: PMC2773846; DOI: 10.1371/journal.pgen.1000738;.
  10. 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. PMID: 19805511; PMCID: PMC2786871; DOI: 10.1128/MCB.00794-09;.
Showing 10 of 64 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 63 publications over 28 distinct years, with a maximum of 6 publications in 1994

YearPublications
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75 E. Newton St Evans Building
Boston MA 02118
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