2007 Dickson Prize Winner
Carol W. Greider, PhD
Daniel Nathans Professor
Director of the Department of Molecular Biology and Genetics
Professor of Oncology
Johns Hopkins University School of Medicine
2007 Dickson Prize in Medicine Lecture
“Telomerase and the Consequences of Telomere Dysfunction”
In 1984, while pursuing her doctorate in molecular biology and working with her mentor, Elizabeth H. Blackburn, PhD, at the University of California, Berkeley, Carol W. Greider discovered an enzyme subsequently named telomerase because it maintains telomeres, the terminal segments of chromosomes that are essential for their replication and stability.
This pioneering discovery, which Greider described as being rooted in the pursuit of “curiosity-driven basic science,” has shaped the focus of her career. She first isolated and characterized telomerase using the single-cell ciliate Tetrahymena, which has 40,000 telomeres and, thus, was a great source for looking for telomere enzymes. Later, as an independent fellow at Cold Spring Harbor Laboratory, where she continued her research career after completing her PhD in 1987, Greider cloned and characterized the RNA component of telomerase. As she advanced there from assistant investigator in 1990 to associate investigator in 1992 and investigator in 1994, her research expanded to include the role of telomere length in cell death and in cancer.
Chromosome ends shorten each time a cell divides. Telomerase adds DNA to the chromosome ends to compensate for this loss during replication. Therefore, telomerase is essential for cells that divide indefinitely and holds tremendous implications for the growth of cancer cells as well as stem cells. Subsequent work by Greider and her collaborators confirmed that inhibiting telomerase can limit cancer cell division and also limit tumor production in mice.
In 1997, Greider moved to Johns Hopkins University School of Medicine, where her group continued to study the biochemistry of telomerase and determined the secondary structure of human telomerase RNA. She expanded her work on a mouse model of telomere dysfunction, showing that the shortest telomere in a cell triggers a DNA damage response. She also established that telomere dysfunction in yeast resembles DNA damage and initiates genomic instability. Her career advancements at Johns Hopkins have included appointments as professor of molecular biology and genetics in 1999, professor of oncology in 2001, and Daniel Nathans Professor and director of the Department of Molecular Biology and Genetics in 2003.
For their groundbreaking work with telomerase, Greider and her former mentor, Blackburn, who is now at the University of California, San Francisco—along with Jack W. Szostak, PhD, of Harvard Medical School—received the 2006 Albert Lasker Award for Basic Medical Research. The Lasker Foundation noted that their research set the stage for subsequent studies linking telomerase and telomeres to human cancer and age-related conditions and indicated that the implications of their work have yet to be exhausted.
“We had no idea when we started this work that telomerase would be involved in cancer but were simply curious about how chromosomes stayed intact,” Grieder remarked following the news of the Lasker Award. “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 continues to study the role that telomerase may play in both cancer and stem cell failure and to look for a clearer link between telomeres and aging. One example of her recent research is an exploration of how mutations in telomerase cause a rare, inherited disorder called dyskeratosis congenita that is related to stem cell failure and that manifests itself as bone marrow failure.
Among Greider’s other honors are the Wiley Prize in Biomedical Sciences, the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science, the Passano Award, and the Gairdner Foundation International Award (all of which she has shared with Blackburn) plus the Lila Gruber Memorial Cancer Research Award and the Richard Lounsbery Award. In addition, she is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and the American Academy of Microbiology.
(Originally published Oct. 11, 2007)