Special Seminar - Eric Batchelor

"p53 dynamics and the regulation of cell stress responses in single cells"

A major regulator of the cellular response to genotoxic stresses, including ionizing radiation, UV light, and oxidative stress, is the transcription factor p53. The temporal pattern of p53 accumulation and degradation, termed p53 dynamics, has been identified as a novel regulatory mechanism for determining cell fate responses to cellular stress. Understanding how distinct stresses are encoded into p53 dynamics and subsequently decoded by p53-dependent transcriptional regulation is a current challenge. To address this challenge, we make use of live-cell approaches including time-lapse fluorescence microscopy to track p53 dynamics and determine cell fate outcomes including cell cycle arrest, cell death, or senescence at the single cell level. Through pharmacological manipulation of p53 dynamics, we are identifying methods to increase the efficacy for induction of specific cell fate outcomes and reduce fractional therapeutic responses caused by cellular heterogeneity.