Carol Greider, one of the world's pioneering
researchers on the structure of chromosome ends known as
telomeres, was named yesterday to share the 2006 Albert
Lasker Award for Basic Medical Research.
First given in 1945, the
Lasker
Awards, often dubbed the "American Nobels," are
considered by many the nation's most prestigious honor for
basic and clinical medical research, primarily because of
the extremely rigorous process of nomination and selection
conducted by a jury of the world's top scientists.
The 2006 award recognizes Greider, the Daniel Nathans
Professor and director of
Molecular Biology and
Genetics in the Johns Hopkins Institute of Basic
Biomedical Sciences, along with Elizabeth H. Blackburn, of
the University of California, San Francisco, and Jack
Szostak, of Harvard Medical School. The three predicted and
discovered telomerase, an enzyme that maintains the length
and integrity of chromosome ends (telomeres) and has drawn
intense interest from researchers studying the role of
telomeres in everything from aging to cancer. The Lasker
Award carries a $100,000 cash prize that will be shared by
the three.
Each time a cell divides, its chromosomes become a
little shorter. As cells age, their telomeres shorten. The
consequent loss of telomere function will cause some cells
to stop dividing or die and others to undergo chromosome
rearrangements that can lead to cancer.
Greider, Blackburn and Szostak performed their
groundbreaking investigations in the late 1970s and 1980s.
Blackburn showed that simple repeated DNA sequences make up
chromosome ends and, with Szostak, established that these
repeated sequences stabilize chromosomes and prevent them
from becoming damaged. Szostak and Blackburn predicted the
existence of an enzyme that would add the sequences to
chromosome termini.
While a graduate student with Blackburn, who was then
a faculty member at Berkeley, Greider tracked down the
enzyme telomerase. She later determined that each
organism's telomerase contains an RNA component that serves
as a template for the creature's particular telomere DNA
repeat sequence. In addition to providing insight into how
chromosome ends are maintained, Blackburn, Greider and
Szostak's work laid the foundation for studies that have
linked telomerase and telomeres to human cancer and
age-related conditions.
A delighted Greider thanked the Lasker Foundation for
the award and emphasized that the recognition highlights
the value of "discoveries driven by pure curiosity."
"We had no idea when we started this work that
telomerase would be involved in cancer," she said, "but
were simply curious about how chromosomes stayed intact.
"What intrigues basic scientists like me is that any
time we do a series of experiments, there are going to be
three or four new questions that come up when you think
you've answered one. Our approach shows that while you can
do research that tries to answer specific questions about a
disease, you can also just follow your nose," Greider
said.
The work was done using a single-celled, pond-dwelling
organism called Tetrahymena. These organisms — rather
than primates or humans — were the best test system,
Greider said, because Tetrahymena contain "more like 40,000
chromosomes, compared to our 23 pairs" and thus have far
more chromosome ends to study.
Stephen Desiderio, director of the Institute of Basic
Biomedical Sciences at Hopkins, said, "Basic research
continues to be the source of most great discoveries. We
are thrilled that Carol is being recognized for her work,
which has shown that by pursuing interesting lines of
research, devising clever experiments to test new ideas and
working with great persistence, one can be extremely
successful."
Greider grew up in Davis, Calif., where her father was
a physicist at the University of California. She credits
her parents for her decision to go into science, and her
father for influencing her attitude about academic science.
"My father would talk about academic freedom and the
importance of liking what you do," she said. "He would say,
'You can do whatever you want, but you have to like
whatever you do.'"
Greider graduated from the University of California,
Santa Barbara, in 1983 with a bachelor's degree in biology
and earned a doctorate in molecular biology in 1987 from
the University of California, Berkeley. She worked at Cold
Spring Harbor Laboratory on Long Island, N.Y., from 1988 to
1997, first as a postdoctoral fellow, then an associate
investigator. She came to Johns Hopkins in 1997.
While at Cold Spring Harbor, Greider, working with
Calvin Harley at McMaster University, realized that cancer
cells, unlike most cells in the adult human body, contain
active forms of telomerase that enable cells to keep
dividing by maintaining the length of their chromosome
ends. Together, in 1990, they provided early evidence that
telomere length was related to cellular aging. They found
that telomerase is activated in cancer cells, allowing
these cells to bypass cellular senescence and continue
growing as immortalized cells.
The two researchers began to imagine a treatment for
cancer in which the telomerase could be inhibited long
enough to wipe out the telomeres in the malignant cells.
This would trigger death in the cancer cells but not in
normal ones with their longer telomeres.
Subsequent work using cultured human cells and mice
genetically engineered to lack the gene for telomerase
confirmed that inhibition of telomerase can limit cancer
cell division and tumor production.
Greider continues to study the role of telomeres in
DNA damage and cell death. Recently, she and her colleagues
developed a mouse model for a rare inherited disorder
related to stem cell failure, dyskeratosis congenita, which
is caused by mutations in telomerase. People with
dyskeratosis congenita cannot maintain the telomerase in
their bone marrow and eventually die of bone marrow
failure. "Suddenly, the studies that we had done on the
consequences of telomerase loss were pertinent to this
disease," Greider said. "It's another example of
curiosity-driven research ending up having a direct medical
implication."
Greider is currently working on mouse models she
helped develop to understand how telomerase may play a role
in both cancer and stem cell failure. This research might
lead to a clearer link between aging and telomeres, she
said. "I don't believe that aging is going to be a matter
of just one thing, that there's going to be one gene that
controls all of aging. I think there are going to be
multiple different failures, and that the loss of stem
cells can play a role in a number of them."
Edward D. Miller, dean of the medical faculty and CEO
of Johns Hopkins Medicine, said, "Carol Greider's
profoundly important work, its impact on science and its
increasing implications for human health exemplify the
Johns Hopkins mission in advancing knowledge for the sake
of our world. We are pleased that the Lasker Foundation has
chosen to honor her, and we offer her our heartiest
congratulations."
The 61st Lasker Awards luncheon will be held on
Friday, Sept. 29, at the Pierre Hotel in New York City.
The last time Johns Hopkins faculty received Lasker
Awards was in 1997, when Victor A. McKusick was honored for
Special Achievement in Medical Science for founding the
formal field of medical genetics, and Alfred Sommer
received the Clinical Research Award for his discovery that
vitamin A supplementation prevents blindness and
life-threatening infections in millions of children living
in the poorest nations in the world.
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Celebration Today
A reception honoring Carol Greider will be held at 4
p.m. today, Sept. 18, on Turner Plaza on the East Baltimore
campus.
Host Edward D. Miller, dean of the medical faculty and
CEO of Johns Hopkins Medicine, said, "Carol Greider's
discoveries and her mentoring of others exemplify the
Hopkins model of advancing basic research to sustain and
improve human health, and train the next generation of
scientists. So come and celebrate this singular honor for
her and the Hopkins family."
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