Agnel Sfeir, PhD

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

Sfeir Lab

Cell Biology, Skirball Institute of Biomolecular Medicine




Contact Information

Skirball Institute of Biomolecular Medicine
540 First Avenue
Floor 4, Lab 3
New York, N.Y. 10016

Office Tel: (646) 501-6742
Lab Tel: (646) 501-6743
Fax: (212) 263-7760

Admin Information

Edna Normand
Tel: (212) 263-6354

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.