My current research focus is on how, and when, cell committ to cellular senescence. Senescence is an irreversible arrest of cell proliferation. This phenotype was first described following the observation that primary cells only undergo a finite number of divisions in culture. It is now known that ‘premature’ or ‘accelerated’ senescence can be triggered by various stresses including DNA damage, hypoxia, activation of oncogenes, or loss of tumor suppressor genes. Furthermore, recent studies in mouse and human tumors have shown that senescence is a potent defense against tumor progression in vivo. Consequently, there is now growing interest in harnessing senescence for cancer treatment.

We recently developed a computational-experimental approach to induce premature senescence in transformed human breast epithelial cells. Our studies revealed that, in response to DNA damage, p53 dynamics can be pharmacologically perturbed to accelerate expression of senescence genes and promote entry into senescence. However, it is still unclear how p53 dynamics are decoded to induce senescence, when this irreversible decision is made, and how the dynamics of entry into senescence differs between transformed and nontransformed cell lines. I hope to address these questions in future studies.