BBS Faculty Member - Elaine Elion

Elaine Elion

Department of Biological Chemistry and Molecular Pharmacology

Harvard Medical School
C1 - 302 / Dept of BCMP
240 Longwood Avenue
Boston, MA 02115
Tel: 617-432-3815
Fax: 617-738-0516
Email: elaine_elion@hms.harvard.edu



Our group studies the specificity of signal transduction pathways that control proliferation, differentiation, and survival. We study these problems in bakers yeast, using classic and modern genetic, molecular and cell biological approaches. We focus on the mating and invasive growth pathways, which provide wonderful examples of hormone- and nutrient-stimulated changes in cell cycle control, polarized growth, cell communication and survival. The pathways that control these events share high conservation with related pathways in higher eukaryotes including humans. A part of our work has centered on defining how mitogen activated protein kinase (MAPK) cascades function in vivo. MAPK cascades form the cores of numerous eukaryotic signal transduction pathways and are misregulated in a variety of diseases, including cancer.

1. Fidelity of MAPK signaling. We are studying how a model scaffold/ MAPK cascade complex functions at several levels. Questions we are addressing include how the proteins assemble at the plasma membrane to allow for activation of the uppermost kinase in the cascade and how the signal is properly transmitted through the MAPK cascade to the nucleus to the right set of genes and not into other pathways that use some of the same signaling components. We are also trying to understand the coordination that allows for proper MAPK signaling and changes in cell polarity that occurs in response to external gradient of mating pheromone. This analysis has led us to study the role of the actin cytoskeleton in mediating assembly of an active signaling complex in vivo and define intersections between heterotrimeric G proteins, Rho proteins and other regulators of the cytoskeleton.

2. Control of cell survival during cell-cell communication. A common feature of development and disease is the programmed destruction of cells. A similar phenomenon occurs during mating. Mating cells respond to an external gradient of mating pheromone by arresting their cell cycles in G1 phase, undergoing polarized growth towards the highest pheromone source, followed by cell –cell aggregation and cell-cell fusion to form a zygote. We have characterized what happens when pheromone stimulated cells are unable to mate and are defining a programmed cell death pathway that involves MAPK cascades, mitochondria and shares features of necrosis and apoptosis. We have identified genes that stimulate the death and inhibit it and wish to define the role of these gene products in regulating programmed cell death. In addition, we have identified several inducers of apoptotic-like death that have counterparts in pathogenic yeast and wish to characterize them.

3. Strain variation and signaling efficiency. Heightened activation of MAPK cascades is implicated in a wide variety of disease states. We found that the basal activity of a MAPK cascade can impact the ability of cells to undergo invasive growth (related to pseudohyphal growth in some pathogenic yeast) and mating and is highly variable depending on the yeast strain. We wish to identify the regulators that determine the set point of the MAPK cascade and clone physiologically relevant differences among yeast strains in order to define the genetic variation.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Andersson J, Simpson, DM, Qi M, Wang, Y and Elion, EA. Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes. EMBO J. 2004; 23 2564-76.

Elion EA, Qi M and Chen W. New insights in signaling specificity in yeast. Science 2005; 307: 687-88.

Wang Y, Chen W, Simpson DM and Elion EA. Cdc24 regulates nuclear shuttling and recruitment of the Ste5 scaffold to a heterotrimeric G protein in S. cerevisiae. J. Biol. Chem, 2005; 280:13084-96.

Lu Y, Qi, M, Sheff, MA and Elion, EA. Counteractive control of cell polarity during mating by MAPK Fus3 and G1 cyclin dependent kinase. Mol. Biol. Cell 2008; 19:1739-1752.



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