"Stem Cells: Coping with Stress"



Elaine Fuchs, Ph.D.

Investigator, Howard Hughes Medical Institute

Rebecca C. Lancefield Professor

Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development

The Rockefeller University



*community lunch to follow presentation

Abstract

Our epithelial tissues form barriers that separate us from the outside world. As such they are subject to a barrage of external assaults, including pathogens, allergens,  wounds and carcinogens. To cope with these stresses, these tissues must constantly be rejuvenated. They do so through resident stem cells, which have the ability to self-renew long term and differentiate to make and maintain the barrier tissue. These stem cells must also be able to sense and respond quickly to injury in order to fuel rapid tissue regeneration. How stem cells balance self-renewal and differentiation is of fundamental importance to our understanding of normal tissue maintenance and wound repair. The regulatory circuitry governing this normal balancing act must be intricately regulated in normal homeostasis, and then transiently altered to cope with injury responses. Increasing evidence suggests that the mechanism goes awry in inflammation and becomes hijacked in cancers.



Skin epithelium is an excellent model system to understand how stem cells remain quiescent during times of minimal wear and tear, how these cells become mobilized during active tissue regeneration and wound-repair, and how the normal process of stem cell activation goes awry in cancer and inflammation. We’ve identified and characterized at a molecular level the skin’s stem cells and shown that they reside in distinct niches that impart to the stem cells their behavior both in task and in the molecular properties they display. We use high throughput genetic and genomic approaches to dissect at a molecular level how stem cell interactions with their microenvironments differ in homeostasis, wound repair and inflammation, and how stem cells acquire and recall memories of their past experiences. These memories can profoundly impact their future behaviors. Finally, we study how heterogeneity in tumor microenvironments emerges from aberrant interactions with oncogenic stem cells. As we show, this heterogeneity leads to stem cells that acquire resistance to chemo and immune therapies.  Our global objective is to apply our knowledge of the basic science of epithelial stem cells to unfold new avenues for therapeutics. 



About the Speaker

Elaine Fuchs is the Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development at The Rockefeller University and an Investigator at the Howard Hughes Medical Institute. Her lab studies the role of skin stem cells in homeostasis and wound repair and how these processes go awry in cancer and inflammatory diseases.  



Fuchs received her B.S. in chemistry from the University of Illinois, Champaign-Urbana and her Ph.D. in biochemistry from Princeton. She studied skin biology as a post-doctoral fellow with Howard Green at the Massachusetts Institute of Technology. Fuchs was a faculty member at the University of Chicago for twenty years before joining Rockefeller University in 2002.



Fuchs’ contributions to skin and stem cell biology have been recognized through honors including the National Medal of Science in 2008, the March of Dimes Prize in 2012, and the E.B. Wilson Prize from the American Society of Cell Biology in 2015. She is a member of the National Academy of Sciences and the National Academy of Medicine.



Research

The Fuchs lab employs high throughput genomics, single cell sequencing, live imaging, cell biology, and functional approaches to unravel the pathways that balance stem cell self-renewal with tissue regeneration. Her team investigates 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 also study the signaling pathways that must be turned on and off at the right time and place for adult skin stem cells to become activated to regenerate tissue. They seek to discover the activating signals from the neighboring cells that instruct the stem cells to make hair or repair wounds, and the inhibitory signals that tell them to stop making tissue.



Overall, Fuchs studies tissue biology at multiple levels, from its stem cells and the signals that control them to the epigenetic, transcriptional, and translational programs that maintain an orchestrated balance of tissue growth. While the foundations of normal tissue homeostasis and injury repair are still unfolding, the fundamental discoveries that Fuchs’s lab has made already provide insights into how skin and its stem cells cope with different environmental stresses, including aging, inflammation, and cancer, offering new avenues for treating human skin disorders.