Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Daniel Lew

Daniel J. Lew, Ph.D.
Professor of Pharmacology and Cancer Biology
Professor of Genetics

Duke University Medical Center
C359 LSRC
Box 3813
Durham, NC 27710

Phone: 919-613-8627
E-mail: daniel.lew@duke.edu
Web site

Research Interests

Our research focuses on the area of cell cycle control, and in particular how it interacts with control of cell polarity. One focus is the study of how changes in the activity of the Cyclin Dependent Kinases (CDKs) that control cell cycle progression promote specific changes in the organization of the actin cytoskeleton. A second focus involves investigation of a novel checkpoint control that monitors the organization of the actin cytoskeleton. When environmental insults disrupt actin organization, this checkpoint delays entry into mitosis through inhibition of CDK/cyclin kinases. Genetic and biochemical approaches are underway to study these signaling pathways in the experimentally tractable budding yeast. A ras-related G protein, Cdc42p, participates in signaling actin reorganization in response to CDK activity. We are tracing the links between the CDK and Cdc42p to understand how a cortical site is specified and polarity is established during the cell cycle. We are also using genetic screens to identify the genes that act together with Cdc42p to polarize the actin cytoskeleton. A tyrosine kinase, Swe1p, is responsible for inhibiting entry into mitosis when the actin cytoskeleton is disrupted. The transcription, localization, and degradation of Swe1p are regulated by the checkpoint, and we are pursuing the basis for this regulation.

Publications

Harrison, J.C., Bardes, E. S. G., and Lew, D. J.: A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint. Nature Cell Biol. 3: 417-420. (2001).

Gladfelter, A.S., I. Bose, T.R. Zyla, E.S. Bardes, and D.J. Lew. Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p. J. Cell Biol. 156:315-326. (2002).

Lew, D.J. The Morphogenesis Checkpoint. Curr. Opin. Cell Biol., 15:648-653. (2003).

Theesfeld, C.L., Zyla, T.R., Bardes, E.S., and D.J. Lew. A monitor for bud emergence in the yeast morphogenesis checkpoint. Mol Biol Cell, 14:3280-3291. (2003).

Lew, D.J. and Burke, D.J. The spindle assembly and spindle position checkpoints. Ann. Rev. Genet., 37:251-282 (2003).

Irazoqui, J.E., Gladfelter, A.S., and Lew, D.J. Scaffold-mediated symmetry breaking by Cdc42p. Nature Cell Biology, 5:1062-1070 (2003).

Irazoqui, J.E. and Lew, D.J. Polarity establishment in yeast. J. Cell Sci., 117, 2169-2171 (2004).

Harrison, J.C., Zyla, T.R., Bardes, E.S.G., and Lew, D.J. Stress-specific activation mechanisms for the “cell integrity” MAPK pathway. J. Biol. Chem., 279: 2616-2622 (2004).

Irazoqui, J.E., Howell, A.S., Theesfeld, C.L., and Lew,D.J. Opposing roles for actin in Cdc42p polarization. Mol. Biol. Cell 16: 1296-1304 (2005).

Gladfelter, A.S., Kozubowski, L., Zyla, T.R., and Lew, D.J. Interplay between septin organization, cell cycle and cell shape in yeast. J. Cell Sci. 118: 1617-1628. (2005).

McNulty, J.J., and Lew, D.J. Swe1p responds to cytoskeletal perturbation, not bud size, in S. cerevisiae. Current Biology 15: 2190-2198 (2005).

Lew, D.J. Cell Polarity: Negative Feedback Shifts the Focus. Current Biology 15: R994-R996 (2005).

Keaton, M., and Lew, D.J. The Morphogenesis Checkpoint: Progress and Controversy. Curr. Opin. Microbiol. 9: 540-546. (2006).

Haase, S.B., and Lew, D.J. Microtubule Organization: Cell Fate is Destiny. Current Biology, r248-r251 (2007).

Keaton, M., Bardes, E.S.G., Marquitz, A.R., Freel, C.D., Zyla, T.R., Rudolph, J., and Lew, D.J. Differential susceptibility of S and M phase cyclin/CDK complexes to inhibitory tyrosine phosphorylation in yeast. Current Biology 17: 1181-1189 (2007).

Tong, Z., Gao, X-G., Howell, A., Bose, I., Lew, D.J., and Bi, E. Adjacent positioning of cellular structures enabled by a Cdc42 GAP mediated zone of inhibition. J. Cell Biol. 7: 1375-1384 (2007).

Top of page