Carol Greider

Academic Titles: 
Daniel Nathans Professor & Director

603 PCTB, 725 N. Wolfe Street
Baltimore, MD 21205-2185

Research Interest: 
Telomeres and telomerase in chromosome maintenance and stability

Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase that synthesizes telomere sequences de novo onto chromosome ends. Telomerase is specialized reverse transcriptase, requiring both a catalytic protein and an essential RNA component. In the absence of telomerase, telomeres shorten progressively as cells divide, and telomere function is lost. For this reason, telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. My lab is focused understanding telomerase and cellular and organismal consequences of telomere dysfunction. We use biochemistry, yeast and mice to examine telomere function. 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 or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. We also are using our telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with this disease die of bone marrow failure, likely due to the stem cell loss. We have developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated.

Lab Members:
Selected Publications:
Kaizer H, Connelly CJ, Bettridge K, Viggiani C, Greider CW. (2015) Regulation of Telomere Length Requires a Conserved N-Terminal Domain of Rif2 in Saccharomyces cerevisiae. Genetics 201:573-586. [ pdf ]
Armanios M, Greider CW. (2015) Treating Myeloproliferation-On Target or Off? New England Journal of Medicine 373(10):965-6. [ pdf ]
Strong MA, Vidal-Cardenas SL, Karim B, Yu H, Guo N, Greider CW. (2011) Phenotypes in mTERT+/- and mTERT-/- Mice are Due to Short Telomeres, Not Telomere-Independent Functions of TERT. Molecular and Cellular Biology 31: 2369-2379. [ link ]
Tom HI, Greider CW. (2010) A Sequence-Dependent Exonuclease Activity From Tetrahymena thermophila. BMC Biochemistry 11:45. [ link ]
Vidal-Cardenas SL, Greider CW. (2010). Comparing effects of mTR and mTERT deletion on gene express and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase. Nucleic Acids Research. 38: 60-71. [ link ]
Craig NL, Cohen-Fix O, Green R, Greider CW, Storz G, Wolberger W. (2010). Molecular Biology: Principles of Genome Function (Oxford, Oxford University Press).
Armanios M, Alder JK, Parry EM, Karim B, Strong MA, Greider CW. (2009). Short telomeres are sufficient to cause the degenerative defects associated with aging. American Journal of Human Genetics. 85, 823-832. [ link ]
Ma Y, Greider CW. (2009). Kinase-Independent functions of TELI in telomere maintenance. Molecular and Cellular Biology. 5193-5202. [ link ]
Morrish TA, Greider CW. (2009). Short telomeres initiate telomere recombination in primary and tumor cells. PLoS Genetics. 5, e1000357. [ link ]
Feldser D, Greider CW. (2007). Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 11, 461-469. [ link ]
Frank CJ, Hyde M, Greider CW. (2006). Regulation of telomere elongation by the cyclin-dependent kinase CDK1. Molecular Cell. 24, 423-432. [ link ]
Hao LY, Armanios M, Strong MA, Karim B, Feldser DM, Huso D, Greider CW. (2005). Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity. Cell. 123: 1121-1131. [ link ]
IJpma A, Greider CW. (2003). Short telomeres induce a DNA damage response in S. cerevisiae. Molecular Biology of the Cell. 14: 987-1001. [ link ]