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Carol Greider

Carol Greider

Department Affiliation: Primary: Molecular Biology and Genetics
Degree: Ph.D., University of California, Berkeley
Rank: Professor
Telephone Number: 410-614-6506
Fax Number: 410-955-0831
Email Address: cgreider@jhmi.edu
Homepage URL:  
http://www.greiderlab.org/
School of Medicine Address: 603 Preclinical Teaching Bldg.,  725 N. Wolfe St., Baltimore, Maryland 21205

Telomeres and telomerase in chromosome maintenance and stabililty 

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 do novo onto chromosome ends.  Telomerase is specialized reverse transcriptase, requiring both a catalytic protein and an essential RNA component.  In the abseces 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 on 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.


Representative Publications:

  • Kass-Eisler, A. and Greider, C.W. Recombination and telomeres.  Trends Biochem. Sci. 25(4):200-204, 2000.  Pub Med Reference


  • Chen, J.-L., Blasco, M., Greider, C.W.   A Secondary structure of vertebrate telomerase RNA.  Cell 100:503-514, 2000.  Pub Med Reference


  • Hemann, M. T., and Greider, C. W.   Wild derived inbred mouse strains have short telomeres.  Nucleic Acids Res. 28:4474-4478, 2000.  Pub Med Reference


  • Chen, Q., Ijpma, A., Greider, C. W.  Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events.  Mol. Cell Biol. 21:1819-1827, 2001.  Pub Med Reference


  • Hemann, M. T., Rudolph, L., Strong, M., DePinho, R. A., Chin, L., Greider, C. W.   Telomere dysfunction triggers developmentally regulated germ cell apoptosis.  Mol. Biol. Cell. 12:2023-2030, 2001.  Pub Med Reference


  • Hackett, J. and Greider, C. W.   Telomere dysfunction increases mutation rate and genomic instability.  Cell 106:275-286, 2001.  Pub Med Reference


  • Hemann, M. T., Strong, M., Hao, L.-Y., Greider, C. W.   The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability.  Cell 107: 67-77, 2001.  Pub Med Reference


  • Ijpma, A. and Greider, C.W.   Short telomeres induce a DNA damage response in S. cerevisiae.  Mol. Biol. Cell 14: 987-1001, 2002.  Pub Med Reference


  • Hackett, J.A. and Greider, C. W.  Balancing instability: Dual roles for telomerase and telomere dysfunction in tumorigenesis.  Oncogene 21: 619-626, 2002.  Pub Med Reference


  • Vidal-Cardenas, S.L. and Greider, C.W.  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 Res. 38(1):60-71, 2010.  Pub Med Reference


  • Tom, H.I. and Greider, C.W.  A sequence-dependent exonuclease activity from Tetrahymena thermophila.  BMC Biochem. 11:45, 2010.  Pub Med Reference


  • Strong, M.A., Vidal-Cardenas, S.L., Karim, B., Yu, H., Guo, N., Greider, C.W.  Phenotypes in mTERT+/- and mTERT-/- mice are due to short telomeres, not telomere-independent functions of TERT.  Mol. Cell Biol. 31:2369-2379, 2011.  Pub Med Reference

Other graduate programs in which Dr. Greider participates:

Biochemistry, Cellular & Molecular Biology
Cellular and Molecular Medicine
Human Genetics and Molecular Biology

 
 
 
 
 
 

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