Analysis of the role of telomerase in stem cells and human diseases
Description Of Research
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.
Selected Publications
Morris BJ, Donlon TA, He Q, Grove JS, Masaki KH, Elliott A, Willcox DC, Allsopp R, Willcox BJ. Genetic analysis of TOR complex gene variation with human longevity: a nested case-control study of American men of Japanese ancestry. J Gerontol A Biol Sci Med Sci. 2015 Feb; 70(2):133-42. PMCID: PMC24589862
Owens JB, Mathews J, Davy P, Stoytchev I, Moisyadi S, Allsopp R. Effective Targeted Gene Knockdown in Mammalian Cells Using the piggyBac Transposase-based Delivery System. Mol Ther Nucleic Acids. 2013 Dec 10; 2:e137. PMCID: PMC24326734
Allsopp R. Short telomeres flirt with stem cell commitment. Cell Stem Cell. 2013 Apr 04; 12(4):383-4. PMCID: PMC23561436
Le Saux CJ, Davy P, Brampton C, Ahuja SS, Fauce S, Shivshankar P, Nguyen H, Ramaseshan M, Tressler R, Pirot Z, Harley CB, Allsopp R. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis. PLoS One. 2013; 8(3):e58423. PMCID: PMC23516479