David E. Levin, PhD
Professor, Molecular & Cell Biology
Biography
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.
Other Positions
- Professor, Virology, Immunology & Microbiology, Boston University Chobanian & Avedisian School of Medicine
- Professor, Molecular & Cell Biology, Boston University Henry M. Goldman School of Dental Medicine
- Member, Genome Science Institute, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences
Education
- University of California, Berkeley, PhD
- University of Massachusetts Amherst, BS
Publications
- Published on 1/15/2025
Lorentzon E, Lee J, Masaryk J, Keuenhof K, Karlsson N, Galipaud C, Madsen R, Höög JL, Levin DE, Tamás MJ. Direct binding of arsenicals to nuclear transport factors disrupts nucleocytoplasmic transport. bioRxiv. 2025 Jan 15. PMID: 39868121.
Read at: PubMed - Published on 2/9/2022
Lee J, Levin DE. Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport. J Cell Biol. 2022 02 09; 221(3). PMID: 35139143.
Read at: PubMed - Published on 10/17/2021
Liu L, Veis J, Reiter W, Motari E, Costello CE, Samuelson JC, Ammerer G, Levin DE. Regulation of Pkc1 Hyper-Phosphorylation by Genotoxic Stress. J Fungi (Basel). 2021 Oct 17; 7(10). PMID: 34682295.
Read at: PubMed - Published on 2/24/2020
Alder-Rangel A, Idnurm A, Brand AC, Brown AJP, Gorbushina A, Kelliher CM, Campos CB, Levin DE, Bell-Pedersen D, Dadachova E, Bauer FF, Gadd GM, Braus GH, Braga GUL, Brancini GTP, Walker GM, Druzhinina I, Pócsi I, Dijksterhuis J, Aguirre J, Hallsworth JE, Schumacher J, Wong KH, Selbmann L, Corrochano LM, Kupiec M, Momany M, Molin M, Requena N, Yarden O, Cordero RJB, Fischer R, Pascon RC, Mancinelli RL, Emri T, Basso TO, Rangel DEN. The Third International Symposium on Fungal Stress - ISFUS. Fungal Biol. 2020 05; 124(5):235-252. PMID: 32389286.
Read at: PubMed - Published on 1/8/2020
Tripathi SK, Feng Q, Liu L, Levin DE, Roy KK, Doerksen RJ, Baerson SR, Shi X, Pan X, Xu WH, Li XC, Clark AM, Agarwal AK. Puupehenone, a Marine-Sponge-Derived Sesquiterpene Quinone, Potentiates the Antifungal Drug Caspofungin by Disrupting Hsp90 Activity and the Cell Wall Integrity Pathway. mSphere. 2020 01 08; 5(1). PMID: 31915228.
Read at: PubMed - Published on 10/16/2019
Laz EV, Lee J, Levin DE. Crosstalk between Saccharomycescerevisiae SAPKs Hog1 and Mpk1 is mediated by glycerol accumulation. Fungal Biol. 2020 05; 124(5):361-367. PMID: 32389298.
Read at: PubMed - Published on 5/29/2019
Lee J, Levin DE. Methylated metabolite of arsenite blocks glycerol production in yeast by inhibition of glycerol-3-phosphate dehydrogenase. Mol Biol Cell. 2019 08 01; 30(17):2134-2140. PMID: 31141459.
Read at: PubMed - Published on 10/30/2018
Lee J, Liu L, Levin DE. Stressing out or stressing in: intracellular pathways for SAPK activation. Curr Genet. 2019 Apr; 65(2):417-421. PMID: 30377756.
Read at: PubMed - Published on 9/19/2018
Liu L, Levin DE. Intracellular mechanism by which genotoxic stress activates yeast SAPK Mpk1. Mol Biol Cell. 2018 11 15; 29(23):2898-2909. PMID: 30230955.
Read at: PubMed - Published on 5/30/2018
Lee J, Levin DE. Intracellular mechanism by which arsenite activates the yeast stress MAPK Hog1. Mol Biol Cell. 2018 08 01; 29(15):1904-1915. PMID: 29846136.
Read at: PubMed
View 67 more publications: View full profile at BUMC