Carol Greider

Academic Titles: 
Daniel Nathans Professor & Director
410-955-3292

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.

 

Biosketch: 
Alumni: 

 

Name Dates in Lab Degree 
Karen Prowse 1990-1994 PhD
Lin Mantell 1991-1994 MD, PhD
Chantal Autexier 1991-1997 PhD
Kathleen Collins 1992-1995 PhD
Maria Blasco 1993-1997 PhD
Karen Buchkovich 1994-1996 PhD
Alyson Kass-Eisler 1995-1999 PhD
Bong-Kyeong Oh 1995-1996 PhD
Siyuan Le 1995-2000 PhD
Stephen Buck 1996-1999 PhD
Michael Rudd 1997-1999 PhD
Kay Keyer Opperman 1998-2002 PhD
Julian J-L Chen 1998-2004 PhD
Qijun Chen 1999-2000 PhD
Ling Qi 2001-2004 PhD
Mary Armanios 2003-2005 MD
Yunmei Ma Karanjawala 2004-2009 PhD
Hui-I Tom 2004-2011 PhD
Nini Guo 2007-2011 PhD
Christopher Viggiani 2010-2012 PhD
Tammy Morrish 2004-2012 PhD

 

Selected Publications:
Wang, S., Pike, A. M., Lee, S. S., Strong, M.A., Connelly, C.J., Greider, C.W. (2017) BRD4 inhibitors block telomere elongation. Nucleic Acids Research. 45(14): 8403-8410.  [ link ] [ pdf ]
Greider, C.W. (2016) Regulating telomere length from the inside out: the replication fork model. Genes & Development 30(13):1483-1491.   [ pdf ]
Lee, S, S., Bohrson, C. Pike, A.M., Whellan, S.J., and Greider, C.W. (2015) ATM kinase is required for telomere elongation in mouse and human cells. Cell Reports 13(8):1623-1632. [ pdf ]
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 ]
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 ]
Greider, C.W. (2010) Telomerase Discovery: The Excitement of Putting Together Pieces of the Puzzle (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 49:7422-7439. [ pdf ]
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 ]
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 ]
Feldser D, Greider CW. (2007). Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 11, 461-469. [ 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 ]
Hemann, M.T., Strong, M., Hao, L.-Y., and Greider, C.W. (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107: 66-77. [ pdf ]
Chen, J.-L., Blasco, M, and Greider, C.W. (2000) A Secondary structure of vertebrate telomerase RNA. Cell 100:503-514. [ pdf ]