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Daniel Lew

James B. Duke Professor
Pharmacology and Cancer Biology
(919) 613-8627
Research Interest: 
Cell cycle
Cell biophysics
Signal transduction
Research Summary: 
Control of cell polarity and its relation to the cell cycle in yeast.
Research Description: 

During the cell cycle, the cyclin-dependent kinases (CDKs) at the center of the cell cycle clock trigger a diverse set of events, including remodeling of the cell's cytoskeleton. A number of internal surveillance pathways called checkpoint controls assess how key events are progressing and, if there is a hitch in some important process, they signal the clock to wait until the defect is corrected. In the past few years we have learned a lot about how the central clock works. However, several central questions remain concerning how the CDKs actually trigger many of the events, and how the checkpoint controls "know" whether things are proceeding according to plan.

We work with the tractable budding yeast as a model system, allowing us to make rapid progress on complex problems. One focus in the lab concerns a checkpoint pathway called the morphogenesis checkpoint, which monitors cytoskeletal polarization and bud formation, and inhibits G2 CDK activation if environmental stresses affect these processes. We are trying to understand how information about the cytoskeleton and cell shape is sensed and transmitted to the CDKs. A second focus concerns cell polarity, which is switched on by G1 CDKs and switched off by G2 CDKs in yeast. We would like to understand how global CDK activation makes cells develop (or dismantle) an asymmetric cytoskeleton. Because the genes and processes we study are highly conserved, we anticipate that learning the answers to fundamental questions in yeast will be relevant and informative for a wide range of organisms.

Symmetry breaking and the establishment of cell polarity in budding yeast.
Johnson JM, Jin M, Lew DJ.
Curr Opin Genet Dev. 2011. 21:740-6.

Modeling vesicle traffic reveals unexpected consequences for Cdc42p-mediated polarity establishment.
Layton AT, Savage NS, Howell AS, Carroll SY, Drubin DG, Lew DJ.
Curr Biol. 2011. 21:184-94.

Singularity in polarization: rewiring yeast cells to make two buds.
Howell AS, Savage NS, Johnson SA, Bose I, Wagner AW, Zyla TR, Nijhout HF, Reed MC, Goryachev AB, Lew DJ.
Cell. 2009. 139:731-43.

Molecular dissection of the checkpoint kinase Hsl1p.
Crutchley J, King KM, Keaton MA, Szkotnicki L, Orlando DA, Zyla TR, Bardes ES, Lew DJ.
Mol Biol Cell. 2009. 20:1926-36.

Symmetry-breaking polarization driven by a Cdc42p GEF-PAK complex.
Kozubowski L, Saito K, Johnson JM, Howell AS, Zyla TR, Lew DJ.
Curr Biol. 2008. 18:1719-26.