Current Research
Stem Cells in Homeostasis, Wound Repair, and Cancer

To heal from wounds and deal with daily wear and tear, skin constantly regenerates itself. Stem cells are key to this renewal process. Using molecular and genetic approaches in cultured cells and mice, Elaine Fuchs's work sheds light on how skin stem cells make and repair tissues, and how this process goes awry in genetic diseases, cancers, and proinflammatory disorders.

Fuchs's team has uncovered many molecules that guide cell divisions in developing skin and control cellular movements during wound repair in adult skin. Some signals turn skin stem cells on, telling them when to make hair and when to repair injuries. Other signals direct stem cells to stop making tissue.

One such inhibitory signal comes from a molecule called TGF-beta that is secreted by immune cells near a tumor’s blood vessels. In studies of skin cancer in mice, malignant stem cells that lack the TGF-beta signal grow uncontrollably, but are sensitive to anticancer therapeutics. In contrast, stem cells that receive the TGF-beta signal grow more slowly, but are resistant to cancer therapies. These cells also invade the surrounding stroma, Fuchs and her colleagues discovered. Their research suggests that the behavior of stem cells within tumors is determined by the stem cells’ genetic mutations as well as differences in the tumor’s microenvironment. The combined effects of both intrinsic and extrinsic factors produce hundreds of changes in gene expression in cancer stem cells that are not present in normal skin stem cells. Fuchs's team wants to study how these changes transform a controlled program of stem cell self-renewal to a chaotic one.

Grants from the National Institutes of Health and the New York State Stem Cell Initiative provided partial support for these projects.

Movie: Fluorescent labeling of stem cells in the skin. The home of stem cells is called a niche. Each hair follicle has a stem cell niche (bulge) located just below the sebaceous glands and above the cycling portion of the follicle that is responsible for growing hair. After injury, the stem cells (green) can migrate up and repair the epidermis, even though in unwounded skin these cells just make hair. [Valentina Greco and Elaine Fuchs].

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