The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences ...of telomere dysfunction. 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. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells.
The lab has 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.
The lab also is using the 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 stem cell loss. The lab has 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.
Research Areas: telomerase
, stem cells
, cell biology