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Studying Stem Cells with Skin

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Elena Ezhkova
Title: Postdoctoral Associate, Rockefeller University
Education: PhD, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 2005
Recommended by: Elaine Fuchs

Elena Ezhkova is using skin as a model system to analyze the processes behind stem cell differentiation. Specifically, Ezhkova is focused on understanding the role of epigenetic regulators, such as chromogen modifications, chromogen modelers, and DNA methylation enzymes, and how they control the commitment of stem cells to undergo differentiation or to self-renew. In addition, she is also looking at the impact of this alteration on the expression of epigenetic regulators of stem cell control and tissue development.

When Ezhkova first began her graduate studies at Cold Spring Harbor Laboratory in early 2001, she spent the majority of her time focused on the biochemical characterization of histone modifications and their role in controlling gene expression. But Ezhkova says she soon wanted to know whether or not these modifications play a role in tissue development, tissue control, stem cell control, and organogenesis. For that, she needed a model system that was well understood. "I decided to move to the skin because I think it's one of the most well-characterized model systems as a tissue and as a place where we know that stem cells are located," Ezhkova says. "We can culture them in vitro and perform in vitro differentiation studies, so it's one of the easiest model system to use to study stem cells."

Although she gained a strong foundation of scientific training and a dedication to research as an undergraduate student in her native Russia, it was not until she arrived at Cold Spring Harbor that she began to learn how to think more creatively when it comes to problem solving and critiquing one's own research. She also cites Elaine Fuchs, the head of the lab at Rockefeller University where she is currently a postdoc, as a huge influence and source of encouragement. "Elaine Fuchs is kind of a model for all of us, not only as a scientist doing exceptional work, but also as a person because of how supportive she is," she says.

One of the biggest challenges that Ezhkova faces is the limitation of current bioengineering techniques to provide a workable in vitro skin model system. "One of the things [that is lacking] is an idea of how to reconstitute the skin as organ, complete with a blood vessel, an epidermis, and a hair follicle," she says. "That will require a lot of bioengineering to make skin as a tissue to study in vitro, so that is a very limiting factor and requires an understanding of stem cell biology and the interaction of the skin cells with the dermal compartments underneath, as well as how the blood and dermal system are integrated in all the pathways."

Publications of Note

In March of 2009, Ezhkova and her colleagues at the Fuchs lab published a paper entitled "Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells" in Cell. For this study, they looked at both the role of Ezh2, an essential polycomb repressor complex component, in controlling proliferative potential of basal progenitors as well as its expression in epidermal progenitors. They showed that PRCs "control epigenetic modifications temporally and spatially in tissue-restricted stem cells. They maintain their proliferative potential and globally repressing undesirable differentiation programs while selectively establishing a specific terminal differentiation program in a stepwise fashion," the abstract says.

And the Nobel goes to...

Ezhkova says if she could win the Nobel Prize, she'd like it to be for "understanding the origin of the skin disease and what are the origin of cells that contribute to tumorigenesis," she says, adding that "if we really pinpoint the origin of cancer stem cells and the difference between them and more differentiated progenies, we can kill a disease."

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