Cell Biology, Developmental Biology
The Rockefeller University
Dr. Fuchs is also Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development at the Rockefeller University.
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.
Elaine Fuchs is fascinated by skin and hair – two very distinct structures that develop from the same skin stem cell. By unraveling the biology of skin stem cells, she hopes to answer a question that has intrigued her for more than two decades: How does a skin stem cell decide to become skin or hair? Understanding normal behavior of these specialized cells is also helping Fuchs learn what happens when their growth goes awry. Her studies have already uncovered the genetic basis of blistering skin diseases as well as clues to the way skin cancers and inflammatory skin disorders develop.
Fuchs's research may also provide insight into the extraordinary characteristics that enable stem cells to develop into distinct tissues and organs. “While there is much promise for stem cells in revolutionizing medicine, we must first learn more about stem cells before we can know whether this might be possible,” she contends.
Unlike most other adult stem cells, skin stem cells can easily be grown in the laboratory. Studies from Fuchs's team have shown that multiple signaling pathways, including the WNT and BMP pathways, influence how these stem cells develop into mature hair follicles. Working together, positive WNT signals and antagonistic BMP signals join forces to activate transcription factors that induce the formation of a hair follicle bud. In the absence of these signals, stem cells develop into skin epidermis.
This line of research may eventually lead to new ways to restore or inhibit hair growth. By exploring how the stem cell reservoir (niche) forms and how stem cells are activated to proliferate and differentiate, Fuchs is adding to our understanding of how skin and hair regenerate. Her team’s work delineating the differences between normal stem cells and cancer-causing stem cells (cancer stem cells) has begun to shed light on how defective stem cells can cause cancers and how they acquire resistance to chemotherapies.
Fuchs believes strongly that research scientists do not operate in a vacuum but rather have an obligation to their larger community, including other scientists, government, and the public. “I feel that the best way I can teach and mentor is to lead by example – through a love and enthusiasm for my science, a dedication to research and an awareness of the medical and ethical implications involved, and by setting up an environment conducive to learning,” she says.