Carol W. Greider, Ph.D.

Tuesday, Sept. 26, 2006, 10 a.m. – 10:30 a.m.

Schiciano Auditorium, Fitzpatrick CIEMAS Building

Telomeres protect chromosome ends and distinguish them from DNA breaks in the cell. Telomere DNA consists of tandemly repeated simple repeated sequences. The chromosome termini are maintained by an enzyme called telomerase.

 

Telomerase is specialized reverse transcriptase that contains a catalytic protein subunit and an essential RNA subunit. The telomerase RNA provides the template for the TTAGGG repeats that are synthesized onto chromosome ends. In the absence of telomerase, telomeres shorten progressively and both chromosome instability and cell death can occur. Although many somatic cells in humans do not express telomerase, most human tumors require it for continued growth, suggesting inhibition of telomerase may inhibit the growth of cancer cells.

 

My lab is focused on understanding the telomerase enzyme mechanism and cellular and organismal consequences of telomere dysfunction. We generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations when telomeres are short, cells die via apoptosis. Crosses of these telomerase null mice to other tumor prone mouse models suggest that under some circumstances tumor formation can be greatly reduced by artificial telomere shortening.

 

We are dissecting the molecular mechanisms of telomere function to understand the subtleties that tip the balance between cell death and genetic instability due to loss of telomere function. In addition, we are using our telomerase null mice to explore the essential role of telomerase in stem cell viability. In the autosomal dominant form of the human genetic disease dyskeratosis congenita, individuals exhibit aplastic anemia and other complications that are likely due to stem cell failure. Mutations in telomerase components cause this stem cell failure. We have developed a mouse model of this disease, which we are using to explore the range of physiological consequences of stem cell loss.

Dr. Greider received a B.A. from the University of California at Santa Barbara in 1983 and a Ph.D. in 1987 from the University of California at Berkeley. In 1984, working together with Dr. Elizabeth Blackburn, she discovered telomerase, an enzyme that maintains telomeres, or chromosome ends. Dr. Greider’s thesis work described the isolation and characterization of telomerase from Tetrahymena. In 1988, Dr. Greider went to Cold Spring Harbor Laboratory where, as an independent Cold Spring Harbor Fellow, she cloned and characterized the RNA component of telomerase.

 

In 1990, Dr. Greider was appointed as an Assistant Investigator at Cold Spring Harbor Laboratory. She expanded the focus of her telomere research to include the role of telomere length in cell death and in cancer. Together with Dr. Calvin Harley, she showed that human telomeres shorten progressively in primary cells. This work, along with work of other researchers, led to the idea that telomere maintenance and telomerase may play important roles in cellular senescence and cancer. Dr. Greider was appointed Associate Investigator at Cold Spring Harbor Laboratory in 1992 and Investigator in 1994. Her lab continued to work on both the biochemistry of telomerase and the role of telomere maintenance in cancer in human and mouse cells.

 

In 1997, Dr. Greider moved her laboratory to the Department of Molecular Biology and Genetics at The Johns Hopkins University School of Medicine. In 1999, she was appointed Professor of Molecular Biology and Genetics and in 2001 she was appointed as a Professor of Oncology. She is currently the Daniel Nathans Professor and Director of the Department of Molecular Biology and Genetics.

 

In 1998, she and Dr. Elizabeth Blackburn shared the Gairdner Foundation International Award and in 1999 they were awarded the Rosenstiel Award and the Passano Award for basic medical research. In 2003, Dr. Greider was elected to the National Academy of Sciences and to the American Academy of Arts and Sciences. She currently directs a group of ten researchers who are focused on understanding telomeres and telomerase and their role in chromosome stability, cancer initiation and progression. She is the author of 51 scientific publications and 27 review articles.