Defining the Signaling Space of p53 Activity Across Species and Tissues
Harvard Medical School
January 25, 2018
Foege N130A, Wallace H. Coulter Seminar Room
The tumor suppressing transcription factor p53 is highly conserved across species and widely expressed across tissues. However, differential effects on radiosensitivity across tissues, and weak conservation of p53 DNA binding sites across species, suggest divergence of p53 function in both contexts. We combined live imaging of cell lines with measurements of p53 signaling in mouse tissues to study variation in p53 oscillatory period across species and its waveform across tissues and cancer types. Complementing these observational datasets with small molecule screening, genome editing, genomics and computational models allowed for the development of a conceptual framework for understanding the p53 ‘signaling space’. I will describe how these results inform our understanding of DNA damage signaling, give an example of the limitations of mouse models in DNA damage contexts, and discuss the design of combinations of targeted and genotoxic cancer therapy.
After a brief stint as an undergraduate analytical chemist researcher (McMaster University), Jacob has spent the last decade studying stress response signaling, first in budding yeast (as a graduate student at the University of California, SF), and more recently in Mammalian Cells (as a postdoc Harvard Medical School). His postdoctoral work has focused on how the highly conserved transcription factor p53 is deferentially regulated across tissues and species.