Telomerase is required to maintain telomeres, the protective cap at the end of chromosomes, in all eukaryotic cells. In mammals, including humans, some somatic cells in adults lack telomerase, and as a consequence, telomeres gradually short during cell division and as a function of age. Stem cells are required to replenish dead or damaged cells throughout life, and therefore telomerase is thought to play an important role in stem cell survival. While telomerase is indeed detectable in many types of human stem cells (unlike mature somatic cells), in some cases, such as in the blood, there isn’t sufficient telomerase to maintain telomere length as these cells divide, and as a consequence, telomeres shorten in all blood cells during aging. On the other hand, male germ cells do have sufficient telomerase to thwart telomere loss during aging. One of the primary goals in my lab is to get a better understanding as to how telomerase activity levels are regulated in different types of stem cells.
Recently, we have performed a screen for transcriptional regulators in embryonic stem cells and found that the transcription factor Hypoxia Inducible Factor 1 alpha (Hif1alpha) is essential for maintainence of functional levels of telomerase in these cells. One of the future goals of our work is get a better understanding as to the role of Hif1alpha in regulating telomerase in other types of stem cells. My lab is also interested in evaluating the therapeutic potential of using stem cells, particularly stem cells derived from the bone marrow, which is a pracxtical source of stem cells in adults, to treat cardiac infarcts using a murine model system.