Heads of Laboratories
Skin harbors our largest reservoirs of stem cells. To maintain the body barrier, epidermis constantly self-renews and hair follicles undergo cyclical bouts of activity. Both stem cell compartments participate in repairing tissue damage after injury. Dr. Fuchs studies where adult stem cells come from, how they make tissues, how they repair wounds and how stem cells malfunction in cancers. Her group focuses on the mechanisms that impart skin stem cells with the ability to self-renew, develop and maintain tissues, and how these cells respond to external cues and depart from their niche to accomplish these tasks.
Skin stem cells have the remarkable capacity to self-renew in culture. Dr. Fuchs’s laboratory couples in vitro studies with transgenic, gene knockout and short hairpin RNA technologies in mice and high throughput genomic analyses 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 hair 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 is accelerating the development of therapeutics to enhance wound repair.
Dr. Fuchs’s lab is also trying to understand how stem cells differentiate into hair follicles, skin epidermis and sweat 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, as well as posttranscripitonal alterations in microRNAs, that change the program of gene expression necessary to develop each skin tissue. Dr. Fuchs’s studies reveal new insights into why stem cells become more limited in their tissue options during development.
Dr. Fuchs’s studies also reveal that cancer cells hijack the normal mechanisms that enable stem cells to transition from quiescence to active tissue generation. Her group has recently isolated and characterized the cells responsible for squamous cell carcinomas, among the most common and life-threatening of human cancers world-wide. They have found that these so-called “cancer stem cells” have many features that distinguish them from normal epithelial stem cells. They are currently using high throughput genomics and genetics to identify the key alterations responsible for tumor growth, information that might be exploited in the future for new cancer therapeutics. A final focus of the group is to uncover how changes in protein expression govern the packing of skin cells into different tissues and how this differs in cancer. 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.
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 2012 March of Dimes Prize in Developmental Biology, 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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