Heads of Laboratories
Investigator, Howard Hughes Medical Institute
Rebecca C. Lancefield Professor
Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development
The largest reservoirs of adult stem cells reside in skin. They continually renew the body’s protective barrier, regenerate hair in cyclical bouts, and repair surface wounds. Dr. Fuchs studies where stem cells come from and how they make and repair tissue throughout life. She explores how stem cells communicate with immune, dermal, and other cells in their environment and how this communication malfunctions in aging and cancers.
Dr. Fuchs’ lab couples in vitro studies with classical genetics, RNAi, and CRISPR-Cas technologies in mice to study the biology of skin stem cells. Her research employs high throughput genomic analyses, live imaging, cell biology, and functional approaches to unravel the molecular pathways that determine the normal balance between stem cell maintenance and differentiation and how this goes awry in cancers. Her team is learning how stem cells establish unique chromatin landscapes and programs of gene expression and how this shifts in response to changes in their local environment. They have found that activating signals from neighboring cells instruct skin stem cells when to make hair and when to repair injuries. Conversely, inhibitory cross talk tells the stem cells when to stop making tissue and rest. This work is accelerating the development of therapeutics to enhance wound repair.
By elucidating the positive and negative signaling pathways that need to be turned on and off at the right time and place for adult skin stem cells to become activated to regenerate tissue, her group began to employ genetic methods to investigate what happens when these signals are deregulated. They learned cancer cells hijack the basic mechanisms that enable stem cells to replenish dying cells and to repair wounds.
A major focus is on squamous cell carcinomas, among the most common and life threatening of human cancers worldwide. The group first used high throughput genomics to delineate the features of so-called “cancer stem cells.” They then devised technology that permits high throughput functional screens for oncogenes and tumor suppressors in mice. By identifying mutations that selectively fuel cancer growth and showing that these alterations also occur in related human cancers, Dr. Fuchs hopes her research will lead to new therapeutics that target cancer stem cells without affecting tissue stem cells.
By studying early steps in malignancy, the group discovered that invading blood vessels and associated inflammatory cells transmit aberrant signals. Nearby tumor-initiating cells respond by reducing proliferation, invading the stroma, and resisting chemotherapy. Further away, tumor stem cells grow faster but show greater sensitivity to drugs. This leads to differences in the behavior of stem cells within the developing tumor arising from heterogeneity in the tumor microenvironment rather than variations in genetic mutations.
How do these stromal aberrations affect the transcriptional and epigenetic programs of stem cells during tumor progression? How do these changes confer drug resistance and how do they affect epithelial polarity, adhesion, and invasiveness within the tumor? Does the epigenetic heterogeneity in tumor stem cells that arises from local variations in the stroma contribute to subsequent genetic heterogeneity within cancers? What is the importance of immune cell cross talk with stem cells in wound repair versus cancer? As the group answers these questions experimentally, they will continue to uncover new links to understanding the process of wound repair, as well as tumor progression and metastasis.
B.S. in chemistry, 1972
University of Illinois, Champaign-Urbana
Ph.D. in biochemistry, 1977
Massachusetts Institute of Technology, 1977–1980
Assistant Professor, 1980–1985
Associate Professor, 1985–1988
University of Chicago
The Rockefeller University
Associate Investigator, 1988–1993
Howard Hughes Medical Institute
White House Outstanding Scientist, 1985
Women in Cell Biology Senior Career Achievement Award, 1997
Cartwright Award, Columbia University, 2002
Novartis/Drew Award, 2003
Dickson Prize, 2004
Federation of American Societies for Experimental Biology Award for Scientific Excellence, 2006
Bering Award, 2006
National Medal of Science, 2009
Charlotte Friend Award, 2010
L’Oréal-UNESCO Award, 2010
Madison Medal, 2011
Passano Award, 2011
Albany Medical Center Prize, 2011
March of Dimes Prize, 2012
Lifetime Achievement Award, American Skin Association, 2013
Kligman-Frost Leadership Award, 2013
Pasarow Award, 2013
Pezcoller Foundation-AACR International Award, 2014
E.B. Wilson Medal, 2015
National Academy of Sciences
National Academy of Medicine
American Academy of Arts and Sciences
American Philosophical Society
Fellow, American Association for the Advancement of Science
Adam, R.C. et al. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature 521, 366–370 (2015).
Oshimori, N. et al. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. Cell 160, 963–976 (2015).
Hsu, Y.C. et al. Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell 157, 935–949 (2014).
Schramek, D. et al. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas. Science 343, 309–313 (2014).
Beronja, S. et al. RNAi screens in mice identify physiological regulators of oncogenic growth. Nature 501, 185–190 (2013).