Mathematics Colloquia and Seminars

Return to Colloquia & Seminar listing

The tumor suppressor p53 oscillates in response to DNA double-strand breaks, a behavior that
has been suggested to be essential to its anti-cancer function. Nearly all human cancers have
genetic alterations in the p53 pathway; a number of these alterations have been shown to be
oncogenic by experiment. These alterations include somatic mutations and copy number
variations as well as germline polymorphisms. Intriguingly, they exhibit a mixed pattern of
interactions in tumors, such as co-occurrence, mutual exclusivity, and paradoxically, mutual
antagonism. Using a differential equation model of p53-Mdm2 dynamics, I employ Hopf
bifurcation analysis to show that these alterations have a common mode of action, to abolish the
oscillatory competence of p53, thereby impairing its tumor suppressive function. In this analysis,
diverse genetic alterations, widely associated with human cancers clinically, have a unified
mechanistic explanation of their role in oncogenesis. In this talk, I will also discuss the role of
physiological oscillations in health and disease broadly.

Read more:
Xiong, L., and Garfinkel, A. (2022). A common pathway to cancer: Oncogenic mutations abolish
p53 oscillations. Progress in Biophysics and Molecular Biology.
https://doi.org/10.1016/j.pbiomolbio.2022.06.002