Lea Harrington

Lea Harrington's group studies the mechanisms by which cells and tissues undergo the process of aging, also termed senescence. This process not only limits tissue renewal and regeneration as we age, senescence can also lead to genome instability and, in some cases, promote cancer. Much remains unknown about the myriad forms of senescence described to date, including how senescent states are defined and interrelated, and precisely how their interdiction may affect age-associated changes in cell and tissue function.

To uncover the complex landscapes that define and regulate senescence, they employ high-throughput, genome-wide methods in model cell systems such as yeast and humans. We have discovered that ​small molecules that promote longevity (e.g. resveratrol, pterostilbene) may act through a previously unappreciated role in DNA replication stress, similar to hydroxyurea. They have also uncovered gene networks that serve to forestall replicative senescence through attenuating the response to cell stress, e.g. via C16orf72, now termed Telomere Attrition and p53 Response Protein 1 (TAPR1)/HUWE1-Associated Protein modifying STress Responses (HAPSTR1). Next, they plan to develop organoid models and single cell lineage tracing/robotic methods to investigate how we can exploit these findings to alter the senescence and aging trajectory in human and mammalian models. The goal is to understand the underlying mechanisms that control these still-poorly defined senescence transitions, including the process called replicative senescence, which occurs when chromosome ends (telomeres) become critically eroded. This understanding, they hope, will open new opportunities to address cell and tissue aging, and may also illuminate new ways to treat vulnerability to infection, cancer, and premature tissue failure across a diverse range of ages.