Brandeis_Talk

On October 12 (Wednesday) at 9am Pacific Time/12pm Eastern Time, I will join the Department of Mathematics at Brandeis University to give a talk at their Mathematical Biology Seminar. I will share my recent paper titled ‘A common pathway to cancer: Oncogenic mutations abolish p53 oscillations’! Many thanks to the labs of Drs. Thomas Fai and Johnathan Touboul for the invitation.

Everyone is welcome. Join us on Zoom!

Abstract:
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. DOI: 10.1016/j.pbiomolbio.2022.06.002