Explosive Evolution Under Stress: the Driving Forces of Cancer Dynamics - Project 1

Investigator: Thea D. Tlsty, PhD
Sponsor: Princeton University

Location(s): United States


The Princeton Physical Sciences-Oncology Center (PPS-OC) acts as the Center Organization and Infrastructure and operational backbone of this PS-OC. It provides the overall communications network, management structure, administrative support, fiscal oversight, and linkage to all the projects and cores of the center.
 Current research is organized around four interconnected projects.

Bacterial Model Ecologies:  Builds on research conducted by the PPS-OC principal investigator Robert Austin (Princeton) using micro-fabrication technologies to create complex bacterial ecosystems with variable stress conditions in order to test may of the fundamental physics-based questions related to the explosive evolution of resistance.

Mammalian Cells and Ecosystems:  Continues the research of PPS-OC senior co-investigator and project team leader, Thea Tlsty (UCSF) using various therapeutic agents and stressors to recapitulate rapid cell evolution and resistance. This project explores the genomic, epigenic and proteomic evolution of breast cancer cell ecology.

The Evolution of Cooperation in the Tumor Microenvironment:  We believe that cooperation can
evolve as byproduct of mutualism among genetically diverse tumor cells and / or host cells.  This hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

Physical Ecology Design and Capabilities:  Providing the overarching model and technology for the PPS-OC, this project, lead by co-investigator and team leader Jim Sturm (Princeton) undertakes to design and fabricate the highly confining and interconnected micro-environments used for culturing both bacteria and mammalian cells. The silicon micro-habitat patches (MHP) developed at Princeton will provide a mechanism to control, analyze and ultimately predict the evolution of resistance.