David E. Levin, Ph.D.
Professor and Chair of Molecular and Cell Biology, BUGSDM
Professor of Microbiology
72 East Concord Street, E430
B.S. University of Massachusetts, Amherst
Ph.D. University of California, Berkeley
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 two-fold. 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.
Our work centers on the molecular mechanisms involved in the activation and signaling output of two stress-activated protein kinase (SAPK) pathways — the Cell Wall Integrity (CWI) pathway, which responds to cell wall challenges during growth and morphogenesis, and the High Osmolarity Glycerol (HOG) pathway, which responds to hyper-osmotic stress. We have found in recent studies that, like mammalian SAPK pathways, these two yeast pathways respond to a wide variety of stress conditions in addition to their well-understood functions in the maintenance of the cell wall and osmotic balance. These stresses include DNA damage, metal toxicity, oxidative stress, organic acid stress, and others. We are currently pursuing a very interesting pair of related questions. Specifically, what are the pathways by which different types of stress stimulate the same SAPKs, and how does their stimulation by these diverse signals result in stress-specific signaling outputs?
- Tripathi, S.K., Q. Feng, L. Liu, D.E. Levin, K.K. Roy, R.J. Doerksen, S.R. Baerson, X. Shi, X. Pan, W.H. Xu, X.C. Li, A.M. Clark and A.K. Agarwal (2020). Puupehenone, a Marine-Sponge-Derived sesquiterpene quinone, potentiates the antifungal drug caspofungin by disrupting Hsp90 activity and the cell wall integrity pathway. mSphere e00818-19.
- Lee, J. and D.E. Levin. (2019) Methylated metabolite of arsenite blocks glycerol production in yeast by inhibition of glycerol-3-phosphate dehydrogenase. Mol. Biol. Cell 30:2134-2140.
- Lee, J., L. Liu, and D.E. Levin. (2018) Stressing out or stressing in: Intracellular pathways for SAPK activation. Curr. Genet. 65(2):417-421.
- Liu, L. and D.E. Levin. (2018). Intracelluar mechanism by which genotoxic stress activates yeast SAPK Mpk1. Mol. Biol. Cell 29:2898-2909.
- Lee, J. and D.E. Levin. (2018). Intracellular mechanism by which arsenite activates the yeast stress MAPK Hob1. Mol Biol. Cell 29:1904-1915.
- Lee, J., W. Reiter, I. Dohnal, C. Gregori, S. Beese-Sims, K. Kuchler, G. Ammerer, and D. E. Levin (2013). MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators. Genes & Dev. 27:2590-2601.
- Beese-Sims, S. E., S-J Pan, J. Lee, E. Hwang-Wong, B. P. Cormack, and D. E. Levin. (2012). Mutants in the Candida glabrata glycerol channels are sensitive to cell wall stress. Euk. Cell, 11:1512-1519.
- Levin, D. E. (2011). Regulation of cell wall biogenesis in Saccharomyces cerevisiae: The cell wall integrity signaling pathway. Genetics, 189: 1145-1175.
- Kim, K-Y and D. E. Levin (2011). Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination. Cell, 144: 745-756.
- Beese, S. E., T. Negishi, and D. E. Levin. (2009). Identification of positive regulators of the yeast Fps1 glycerol channel. PLoS Genetics, 5: e1000738.
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