Heads of Laboratories
Rebecca C. Lancefield Professor; Investigator, HHMI
Laboratory of Mammalian Cell Biology and Development
Elaine.Fuchs@rockefeller.edu
Skin is one of the body’s major reservoirs of stem cells, as the epidermis must constantly self-renew to repair damage caused by mechanical stress and injuries. Dr. Fuchs is interested in elucidating the molecular mechanisms that impart skin stem cells with the ability to self-renew, develop and maintain epidermis and hair follicles, and how these cells respond to external cues, depart from their niche and accomplish these tasks.
Skin stem cells have the remarkable capacity to self-renew in culture. Fuchs’s laboratory couples in vitro studies with transgenic, gene knockout, microarray and shRNA technologies in mice to unravel the molecular pathways that determine the normal balance between stem cell maintenance and differentiation, and how this goes awry in cancers. They are learning how embryonic and adult stem cells establish unique programs of gene expression that determine when they divide and what types of cells they develop into. Recent work in the Fuchs lab has shown that a structure at the base of each strand of hair, the hair follicle, uses mesenchymal-epithelial interactions to acquire a threshold of activating signals that instruct stem cells to divide during periods of growth. After the regeneration period, differentiated cells along the lineage return back to the niche. They bring inhibitory signals that tell the stem cells that the hair cycle is complete, so that they return to quiescence. These mechanisms provide new insights into how stem cells become activated to repair tissue upon injury and how they know when to quit once the wound is repaired. The work may accelerate the development of therapeutics that accelerate wound-repair, and others that prevent tissue overgrowth in hyperproliferative conditions such as cancers.
Fuchs’s lab is also trying to understand how stem cells differentiate into hair follicles, skin epidermis and sebaceous glands. They have shown that different positive and negative signaling pathways need to be turned on and off at the right time and at the right place for adult skin stem cells to become hair follicles versus epidermis. These signaling pathways control distinct transcription factors and epigenetic modifications that change the program of gene expression necessary to develop each skin tissue. Fuchs’s studies reveal new insights into why stem cells become more limited in their tissue options during development.
While transcriptional regulation orchestrates tissue development from stem cells, posttranscriptional regulation fine tunes the process. Important in this regard are microRNAs. After documenting an essential role for microRNA function in the skin, Fuchs’s lab has now begun to tease apart the unique roles that individual microRNAs play in development and cancer. In 2008, they reported that a microRNA, microRNA-203, participates in the switch that commits an epidermal stem cell to stop proliferating and terminally differentiate to form the skin’s protective barrier. Most recently, they reported on the global repertoire of microRNAs preferentially expressed in the hair follicle stem cells. A final focus of the group is to uncover how changes in protein expression govern the packing of skin cells into different tissues. How is the cytoskeleton polarized to orient the mitotic spindle? How do the cells reorient their cytoskeleton in response to injury so that the cells can migrate into the wound site? How can cells adhere to one another and yet dynamically turn over the skin epithelium to generate a brand new epidermis and regrow hairs? As the group probes deeper into understanding how stem cells make different kinds of tissues, they continue to uncover new links to understanding the process of wound repair as well as tumor progression and metastasis.
CAREER
Dr. Fuchs received her B.S. in chemistry from the University of Illinois, Urbana-Champaign, in 1972 and her Ph.D. in biochemistry in 1977 from Princeton University. She was a postdoc at the Massachusetts Institute of Technology from 1977 to 1980. Dr. Fuchs was the Amgen Professor of Basic Sciences at the University of Chicago before coming to Rockefeller in 2002. She was named the Rebecca C. Lancefield Professor the same year. She has been a Howard Hughes Medical Institute investigator since 1988.
Dr. Fuchs has received a number of honors and awards, including the 2011 Albany Medical Center Prize in Medicine and
Biomedical Research, 2011 Passano Prize, 2011 Madison Medal, 2010 L’Oréal-UNESCO Award in the Life Sciences, 2010
Charlotte Friend Award from the American Association for Cancer Research, 2009 National Medal of Science from the President
of the United States, the Bering Award and the Federation of American Societies for Experimental Biology Award for Scientific
Excellence in 2006, the Dickson Prize in Medicine in 2004, the Novartis/Drew Award in Biomedical Research in 2003, the
Cartwright Award from Columbia University in 2002 and the Women in Cell Biology Senior Women’s Career Achievement Award
in 1997. She is a member of the National Academy of Sciences and its Institute of Medicine, the American Academy of Arts and
Sciences and the American Philosophical Society. She was named one of the Nation’s Outstanding Scientists by the White House in
1985 and holds honorary doctorates from the University of Illinois and the Mount Sinai and New York University Medical Schools.
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