Agnel Sfeir

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Agnel Sfeir

Assistant Professor, Department of Cell Biology

Contact Info

646/501-6742
Agnel.Sfeir@med.nyu.edu


Research Summary

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.

Polymerase theta is a robust terminal transferase that oscillates between three different mechanisms during end-joining
Kent, Tatiana; Mateos-Gomez, Pedro A; Sfeir, Agnel; Pomerantz, Richard T. Polymerase theta is a robust terminal transferase that oscillates between three different mechanisms during end-joining. eLife. 2016 Jun 17;5:?-? (2145252)

Stop pulling my strings - what telomeres taught us about the DNA damage response
Lazzerini-Denchi, Eros; Sfeir, Agnel. Stop pulling my strings - what telomeres taught us about the DNA damage response. Nature reviews. Molecular cell biology. 2016 May 11;17(6):364-378 (2107652)

Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis
Pinzaru, Alexandra M; Hom, Robert A; Beal, Angela; Phillips, Aaron F; Ni, Eric; Cardozo, Timothy; Nair, Nidhi; Choi, Jaehyuk; Wuttke, Deborah S; Sfeir, Agnel; Denchi, Eros Lazzerini. Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis. Cell reports. 2016 May 26;15(10):2170-2184 (2125042)

The role of mammalian polymerase theta in DNA repair
Sfeir, A. The role of mammalian polymerase theta in DNA repair [Meeting Abstract]. FASEB journal. 2016 April 2016;30(no):- (2167562)

Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination
Mateos-Gomez, Pedro A; Gong, Fade; Nair, Nidhi; Miller, Kyle M; Lazzerini-Denchi, Eros; Sfeir, Agnel. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature. 2015 Feb 2;518(7538):254-257 (1463292)