Department of Cell Biology and Physiology
660 S. Euclid Ave.
Box 8228
St. Louis, MO 63110-1093

Phone:   314-362-7437
Lab:   314-362-7449
Fax:   314-362-7463

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Washington University

Normal human cells possess a limited replicative lifespan whereas cancer cells divide indefinitely and are therefore thought of as immortal. Indeed, cellular immortality is one of the defining characteristics of malignant cell growth. In contrast to what is observed in transformed cells, a limited proliferative capacity (i.e. "cell mortality") is thought to contribute to diseases characterized by high cellular turnover, such as cirrhosis and AIDS. For these reasons, elucidation of the molecular mechanisms that control cellular mortality will have far reaching implications in the fields of oncogenesis, aging, diseases characterized by high cellular turnover, and tissue regeneration.

Understanding how cellular lifespan is controlled at the molecular level is a central theme in the laboratory. Because the telomere, a DNA-protein structure located at the termini of linear chromosomes, plays a central role in controlling cellular mortality, we are particularly interested in understanding how this structure is maintained. To this end the lab is focused on identifying novel proteins that directly interact with the telomere and delineating their role in normal telomere function as well as what role they may play in aged and transformed cells. In addition, delineating the signal transduction machinery that is responsible for monitoring the telomere state and eliciting modifications of the telomere in both normal and transformed cells is of critical importance to understanding how incipient cancer cells obtain immortality.

Chromosomes terminate in telomeres, DNA-protein structure required for genomic stability. Below are FISH (left) and Co-FISH analysis utilizing PNA probes against the telomeric sequence. Co-FISH allows us to identify telomeres replicated by lagging strand synthesis (green) and leading strand synthesis (red).


Senescent cells accumulate with age. Simultaneously, genetic mutations arise creating preneoplastic cells. This model predicts that a senescent cell possessing growth-stimulating properties will arise in the proximity of a preneoplastic cell capable of responding, facilitating tumor formation.

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