04/12

April 12, 2019 . EVENTS

Distinguished Speakers Series for Scientists

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Inaugural seminar in a series of quarterly lectures from leaders in the field.

Elaine Fuchs, Ph.D.
Rebecca C. Lancefield Professor, The Rockefeller University
Investigator, Howard Hughes Medical Institute

Stem cells in silence, action and cancer

Abstract:  My laboratory uses mouse skin to understand how epithelial stem cells remain quiescent during times of minimal wear and tear, how these cells become mobilized during wound-repair and tissue growth, and how the normal process of stem cell activation goes awry in inflammation and cancer. Using functional analyses, we’ve characterized skin stem cells in homeostasis, wound repair, inflammation, and cancer. Using high throughput genetic and genomic approaches, we’ve performed in vivo genome-wide RNAi screens for oncogenes, tumor-suppressors and microRNAs in skin malignancies.  We’ve shown that stem cells respond to such oncogenic stresses by activating the ‘integrated stress response’, which turns out to be essential for their survival and translation of oncogenic mRNAs. Using in vivo chromatin landscaping and lineage-tracing, we’ve also learned that early in tumorigenesis, epithelial stem cells activate a transcriptional program resembling wound-repair. However, they deviate when HRas/MAPK and pETS2 transcription factor levels rise, leading to chromatin remodeling that makes the wound-activated response permanent. Digging deeper, we devised a method to genetically induce tumor formation and progression, and to fluorescently tag and lineage-track tumor stem cells whenever a blood vessel approaches. We learned that this perivasculature microenvironment elicits a TGFβ signal that leads to stabilization of NRF2 in the tumor stem cells, which in turn leads to downstream activation of glutathione genes, rendering the stem cells resistant to chemotherapeutics and radiation. In this TGFβ-rich microenvironment, these tumor stem cells also undergo an EMT-like transition and become invasive. Together, our findings have unearthed relations between normal and tumor-initiating stem cells and reveal how at the chromatin, transcriptional and translational levels, cancer stem cells cope with their stressful and ever-changing microenvironments to survive and resist cancer therapies. Our global objective is to apply our knowledge of the basic science of epithelial stem cells to unfold new avenues for therapeutics.

 

Time
8:00 am - 10:30 am PT

- 3:00 pm - 4:00 pm Seminar
- 4:00 pm - 5:30 pm Reception
Venue
Buck Institute

8001 Redwood Blvd
Novato, California 94945

Elaine Fuchs, PhD
Rebecca C. Lancefield Professor, The Rockefeller University
Investigator, Howard Hughes Medical Institute

The largest reservoirs of adult stem cells reside in skin where they renew the body’s protective barrier, regenerate hair in cyclical bouts, and repair surface wounds. Dr. Elaine Fuchs studies the molecular mechanisms by which skin stem cells make and repair tissues and how these processes breakdown during aging, and in cancer and inflammatory diseases. Throughout her career, Dr. Fuchs has made groundbreaking discoveries in understanding how tissues repair injuries and how abnormalities in stem cell behavior can lead to cancers. In addition to these breakthroughs, she has devised and employed innovative and imaginative approaches to solve problems in biomedical science over three decades. Dr. Fuchs pioneered the field of reverse genetics and has used this approach to elucidate the genetic basis for several skin disorders and tumors. Her lab uncovered the pathways necessary for epithelial stem cells to differentiate into the epidermis, hair follicles, and sweat glands and developed a technique to label, track, and purify quiescent, slow-proliferating stem cells. She was also among the first to describe a cancer stem cell, characterizing how squamous cell carcinoma is initiated. Alongside her considerable scientific contributions, Dr. Fuchs provides thoughtful mentoring for her trainees and is a leading advocate for women in science.

Dr. Fuchs received her Ph.D. in Biochemistry from Princeton University, and conducted her postdoctoral research with Dr. Howard Green at the Massachusetts Institute of Technology. She joined the faculty at the University of Chicago in 1980 and relocated to The Rockefeller University in 2002. Dr. Fuchs’ awards and honors include the Presidential Young Investigator Award, the Richard Lounsbery Award from the National Academy of Sciences, the Novartis-Drew Award for Biomedical Research, the Dickson Prize in Medicine, the FASEB Award for Scientific Excellence, the Beering Award, the National Medal of Science, the L’Oreal-UNESCO Award and Charlotte Friend Memorial Award from the American Association for Cancer Research. In 2011, she received the Madison Medal, Passano Award, and Albany Prize in Medicine (with Shinya Yamanaka and James Thompson), and in 2012 received the March of Dimes Prize (with Howard Green). She received the Kligman-Frost Leadership Award from the Society of Investigative Dermatology, the Lifetime Achievement Award from the American Skin Foundation and the Pasarow Award for Cancer Research in 2013 and the Pezcoller Foundation-AACR International Award in 2014. She received the E.B. Wilson Prize from the American Society of Cell Biology in 2015 and the Vanderbilt Prize in Biomedical Science in 2016. She recently won the Howard Taylor Ricketts Award and the McEwen Award for Innovation. Dr. Fuchs is an elected member of the National Academy of Sciences, The Institute of Medicine, American Academy of Arts and Sciences, American Philosophical Society, European Molecular Biology Organization (foreign member) and Academy of the American Association for Cancer Research. She holds honorary doctorates from Mt. Sinai/New York University School of Medicine and from the University of Illinois, Champaign-Urbana. Dr. Fuchs is also a past President of the American Society of Cell Biology, a recent President of the International Society for Stem Cell Research and is on the Board of Governors of the New York Academy of Sciences. She has trained over 25 graduate students and 100 postdoctoral fellows, many of whom are now independent researchers at major academic universities and medical schools throughout the world.

More information about her research:
Why wounds heal more slowly with age
Fuchs lab website

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The Buck Institute is located 25 miles north of the Golden Gate Bridge.

San Francisco Airport/San Francisco/South Bay:

  • Take Highway 101 North across the Golden Gate Bridge
  • Take the last Novato exit — Atherton/San Marin Drive (just north of the DeLong exit)
  • Turn left at the stoplight, and go west over the freeway overpass
  • Get in the right lane, and turn right at the second stoplight onto Redwood Boulevard
  • Go approximately ½ mile, and turn left onto Buck Center Drive
  • At the top of the hill, turn left into the Visitor Parking Lot

Berkeley/Oakland/Oakland International Airport:

  • Take Highway 80 to Highway 580 West, and cross the Richmond/San Rafael Bridge
  • Take 580 until it merges with Highway 101 North in San Rafael
  • Take the last Novato exit — Atherton/San Marin Drive (just north of the DeLong exit)
  • Turn left at the stoplight, and go west over the freeway overpass
  • Get in the right lane, and turn right at the second stoplight onto Redwood Boulevard
  • Go approximately ½ mile, and turn left onto Buck Center Drive
  • At the top of the hill, turn left into the Visitor Parking Lot

From Sonoma County, take Highway 101 South:

  • Take the first Novato exit (Atherton/San Marin Drive)
  • Turn right at the stoplight, and stay in the right lane
  • Take an immediate right onto Redwood Boulevard
  • Go approximately ½ mile, and turn left onto Buck Center Drive
  • At the top of the hill, turn left into the Visitor Parking Lot

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