Agnel Sfeir

Assistant Professor, Skirball Institute of Biomolecular Medicine, Developmental Genetics. Department of Cell Biology

Ph.D., 2006 University of Texas Southwestern Medical Center

Lab Website: http://saturn.med.nyu.edu/research/dg/sfeirlab/Agnel_Sfeir_Laboratory.html

Keywords: Telomere, Telomerase, Stem Cells, Chromosomes

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 4th floor, Lab 3
New York, N.Y. 10016
Office Tel: (646) 501-6742
Lab Tel: (646) 501-6743
Fax: (212) 263-7760
E-mail: agnel.sfeir@med.nyu.edu

Administrative Contact:

Dolly Chan
Tel: (212)263-7595
Email: dolly.chan@med.nyu.edu


Telomere maintenance in mammalian cells

In normal human somatic cells, telomeres progressively shorten with ongoing cellular divisions due to the inability of the DNA replication machinery to copy each chromosome until the very end. When a subset of telomeres within a cell becomes short, a DNA damage signal is triggered to activate the p53 and Rb pathways that ultimately induce cellular senescence. This is known as the Hayflick limit and is the basis of the tumor suppressive function of telomere shortening.

Cells that accumulate mutations in the checkpoint pathways are capable of bypassing this stage and proliferate further, resulting in additional telomere shortening. This is followed by complete telomere erosion, which engages DNA repair machineries, leading to a stage of extensive chromosome instability, known as crisis. Very few cells can bypass both senescence and crisis and they do so by upregulating telomere maintenance pathways, which either involve activating telomerase or inducing telomere recombination. These cells are then able to progress and become the increasingly aggressive tumors. This scenario highlights the importance of fully understanding telomere maintenance and homeostasis in mammalian cells, which is the focus of our lab.

Selected Publications:

Removal of shelterin reveals the telomere end-protection problem
. Sfeir, Agnel and de Lange, Titia
2012 May 4; 336 (6081):593-597 Science. PMID: 22556254

Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. 
Sfeir, Agnel; Kabir, Shaheen; van Overbeek, Megan; Celli, Giulia B; de Lange, Titia
2010 Mar 26;327(5973):1657-1661, Science. PMID: 20339076

Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. 
Sfeir, Agnel; Kosiyatrakul, Settapong T; Hockemeyer, Dirk; MacRae, Sheila L; Karlseder, Jan; Schildkraut, Carl L; de Lange, Titia
2009 Jul 10;138(1):90-103, Cell. PMID: 19596237

Telomere extension occurs at most chromosome ends and is uncoupled from fill-in in human cancer cells. 
Zhao, Yong; Sfeir, Agnel J; Zou, Ying; Buseman, Christen M; Chow, Tracy T; Shay, Jerry W; Wright, Woodring E
2009 Aug 7;138(3):463-475, Cell. PMID: 19665970

Telomere-end processing the terminal nucleotides of human chromosomes. 
Sfeir, Agnel J; Chai, Weihang; Shay, Jerry W; Wright, Woodring E 2005 Apr 1;18(1):131-138, Molecular Cell. PMID: 15808515

Click here to see all publications in PubMed