Abstract

Individual human cancer cells often show different responses to the same treatment. In this talk I will share the quantitative experimental approaches my lab has developed for studying the fate and behavior of human cells at the single-cell level. I will focus on the tumor suppressor protein p53, a transcription factor controlling genomic integrity and cell survival. In the last several years we have established the dynamics of p53 (changes in its levels over time) as an important mechanism controlling gene expression and guiding cellular outcomes. I will present recent studies from the lab demonstrating how studying p53 dynamics in response to radiation and chemotherapy in single cells can guide the design and schedule of combinatorial therapy, and how the p53 oscillator can be used to study the principles and function of entertainment in Biology. I will also present new findings suggesting that p53’s post-translational modification state is altered between its first and second pulses of expression, and the effects these have on gene expression programs over time.