
Agnel Sfeir, PhD
Skirball Institute
Associate Professor, Department of Cell Biology
The linearity of chromosomes creates two major problems for eukaryotic cells: the end replication problem and the end protection problem. The former stems from the inherent inability of the replication machinery to fully duplicate linear templates. The latter refers to the propensity of linear chromosome ends to be recognized as DNA double stranded breaks. To surmount both problems, cells use telomeres, the specific nucleoprotein complexes that are essential to ensure genomic stability and promote cellular survival. In mammalian cells, telomeres consist of long tracts of repetitive DNA sequences (TTAGGG) that are bound by a specialized six-subunit protein complex termed shelterin. Telomeres are replenished by telomerase, a reverse transcriptase that is active in the germ line and during early embryonic development. Normal human somatic cells lack the activity of telomerase and gradually loose telomeric repeats during progressive division cycles until they ultimately undergo cellular senescence. Our lab is mainly interested in understanding the basic mechanism that leads to telomere length resetting. In particular, we rely on nuclear reprograming as a platform to identify factors that regulate telomere length. A second area of interest to us is to understand how telomere dynamics impact stem cell function and leads to tumorigenesis, using the mouse as a model organism.
646-501-6742
540-562 First Avenue
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New York, NY 10016
Associate Professor, Department of Cell Biology
PhD from Southwestern University
Nature structural & molecular biology. 2017 Oct 23; 24(12):1116-1123
Molecular cell. 2017 Jan 19; 65(3):527-538.e6
Oncotarget. 2016 Jul 26; 7(30):46833-46834
Cell reports. 2016 Jun 07; 15(10):2170-2184
Nature reviews. Molecular cell biology. 2016 Jun; 17(6):364-378
The role of mammalian polymerase theta in DNA repair [Meeting Abstract]
FASEB journal. 2016 APR; 30:?-?
Cell reports. 2015 Nov 24; 13(8):1633-1646

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