Tumor-Suppressor p53 Pathway Modeling       

Medical, Health Informatics and Computational Biology Accomplishment | 2005

IBM researcher: Gustavo A. Stolovitzky

Where the work was done: IBM T.J. Watson Research Center

What we accomplished: The human genome contains about 20,000 genes. Of these, p53 is one of the most important tumor suppressor genes, acting as the key guardian of our genome. In fact, p53 is disrupted in a very high fraction of cancers and is of utmost clinical relevance. Work by IBMers and colleagues presented a highly-cited model of how p53 responds to radiation, enabling insights into the temporal behavior of p53 oscillations resulting from radiation, which may have important implications for cancer treatment.

Related links: A Plausible Model for the Digital Response of p53 to DNA Damage (PNAS, 255 citations as of May 5, 2016): "Cells under stresses such as DNA damage, hypoxia, and aberrant oncogene signals trigger their internal self-defense machinery. One critical response is the activation of the tumor suppressor protein p53, which transcribes genes that induce cell cycle arrest, DNA repair, and apoptosis . . . [W]e present a model for the digital, undamped oscillatory p53 activity . . . [W]e replicate the variable number of p53 pulses in individual cells as well as the cell population dynamics."

A Single Nucleotide Polymorphism in the MDM2 Gene Disrupts the Oscillation of p53 and MDM2 Levels in Cells, W Hu, Z Feng, L Ma, J Wagner, JJ Rice, G Stolovitzky, AJ Levine
Cancer research 67 (6), 2757-2765 (2007); Cited 106 times by May 5, 2006).

p53 – M dm2 Loop Controlled by a Balance of Its Feedback Strength and Effective Dampening Using ATM and Delayed Feedback, J Wagner, L Ma, JJ Rice, W Hu, AJ Levine, GA Stolovitzky
Systems biology 152 (3), 109 (2005); Cited 70 times by May 5, 2006.

Stability and time-delay modeling of negative feedback loops, J Wagner, G Stolovitzky
Proceedings of the IEEE 96 (8), 1398-1410 (2008); Cited 13 times by May 5, 2006.

Image credit: Columbia University