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.
