Heads of Laboratories
Rebecca C. Lancefield Professor; Investigator, HHMI
Laboratory of Mammalian Cell Biology and Development
fuchslb@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 how skin stem cells self-renew, develop and maintain the epidermis and hair follicles, and in the molecular mechanisms that enable these cells to respond to various external cues, depart from their niche and accomplish these tasks.
The skin epithelium is one of the few tissues of the body from which human and mouse stem cells can be maintained and propagated in culture. Hence, it is readily accessible for genetic inquiry and provides an ideal system to study stem cells and dissect their molecular mechanisms of self-renewal and maintenance. Dr. Fuchs’s laboratory studies how skin stem cells behave in vitro and exploits transgenic, gene knockout, microarray and shRNA technologies in mice to reveal how aberrant stem cell behavior in vivo can lead to a variety of disorders, including cancer. Specifically, Dr. Fuchs’s lab is interested in the molecular pathways that determine cell fate, and 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 a two-step mechanism to activate its stem cells and order them to divide. The mechanism provides insights into how repositories of stem cells may be organized in other body tissues for the purpose of supporting organ regeneration.
Another major focus of the Fuchs lab is to understand how these stem cells differentiate into hair follicles, skin epidermis and sebaceous glands. They have shown that BMP and Wnt signaling pathways act in opposition and 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, and that these pathways control distinct transcription factors that may be key components in developing new treatments for thinning hair. Most recently, they have shown how epigenetics collaborates with transcription factors to influence the development and differentiation of the skin’s multiple layers, revealing new insights into how stem cells might become more restricted in their tissue options during embryonic and postnatal development.
The Fuchs lab also has shown that microRNAs participate in fine-tuning these skin differentiation programs, and has now begun to tease apart the unique roles that individual microRNAs play in skin development. In 2008, they were the first to report 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.
Dr. Fuchs is working to understand how changes in protein expression lead to the organization of skin cells into different tissues. How is the cytoskeleton polarized to orient the mitotic spindle in the right direction? How do the cells reorient their cytoskeleton in response to injury so that the cells can migrate into the wound site? How do cells adhere to one another and yet remain able to dynamically turn-over the skin epithelium to generate a brand new epidermis and regrow hairs? In the past year, Dr. Fuchs and her colleagues have used genetics, biochemistry and videomicroscopy to uncover proteins that participate in coordinating the actin and microtubule cytoskeleton. By perturbing these mechanisms, 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 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. In 1994 Dr. Fuchs was elected to the Institute of Medicine of the National Academy
of Sciences and the American Academy of Arts and Sciences. She was elected to the American Philosophical Society in 2005 and the
NAS in 1995. 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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