The physical ends of chromosomes, known as telomeres, play critical roles in cancer development, other age-related disorders and short telomere syndromes. Telomeres protect chromosomes from degradation and rearrangements that are typically seen in cancer. Telomeres also serve as cellular clocks. They shorten in the absence of telomerase limiting cellular lifespan. In most tumors, telomerase is upregulated in order to counteract telomere shortening. Through the expression of telomerase, most human cancer cells acquire an immortal phenotype. In a subset of cancers, however, telomeres are maintained by a DNA recombination-based mechanism termed ALT (alternative lengthening of telomeres).
Our laboratory combines telomeric chromatin analysis by mass spectrometry, biochemistry and molecular genetics to study the dynamics of telomere structure, function and replication in human cells under normal and pathological situations. Our work may allow manipulation of telomere functions in tumors and other diseased tissues in the future.