The Princeton Physical Sciences-Oncology Center

Thursday, Feb 21, 2013

The evolution of bacterial resistance to antibiotics serves as a model for how cancer cells become resistant to treatment. In this experiment, a silicon-based micro-environment where nutrients (LB) are scarce serves to enable the study of how bacterial cells become resistant to an antibiotic (CIPRO). (Image courtesy of Robert Austin)Cancer is one of the most deadly diseases, yet current treatments are available for only a subset of cancers. The Princeton Physical Sciences-Oncology Center (PPS-OC) takes an innovative approach to the study of cancer by exploring the physical laws that govern its emergence and behavior. Funded by the National Cancer Institute, the PPS-OC includes collaborators at the University of California-San Francisco, Johns Hopkins University, the University of California-Santa Cruz and the Salk Institute for Biological Studies.

Research at PPS-OC combines the physical sciences with cancer biology, employing a rigorous approach to investigating how cancer cells evolve to become resistant to drugs and invade the surrounding tissues of the body. The center is organized around four interconnected approaches:

Bacterial Model Ecologies:  Researchers at Princeton are studying how cancer cells evolve and evade elimination by drugs using as a model bacterial cells housed in micro-fabricated environments. This area of research, led by PPS-OC principal investigator Robert Austin, a professor of physics at Princeton, explores the evolution of resistance under various stress conditions.

Mammalian Cells and Ecosystems:  Researchers at University of California-San Francisco are using various therapeutic agents and stressors to recapitulate rapid cell evolution and resistance. This project, led by PPS-OC senior co-investigator and project team leader Thea Tlsty, explores the genomic and proteomic evolution of breast cancer cell ecology.

Mechanical Signaling and Metastasis: Researchers at Johns Hopkins University led by PPS-OC co-investigators Kenneth Pienta and Donald Coffey are conducting a generalized “mechanical” analysis of cancer cells by examining stress-induced changes that play a critical role in evolution.

Physical Ecology Design and Capabilities:  Providing the overarching model and technology for the PPS-OC, this project, led by co-investigator and team leader James Sturm, Princeton's William and Edna Macaleer Professor of Engineering and Applied Science, is focused on the design and fabrication of the highly confining and interconnected micro-environments used for culturing both bacteria and mammalian cells.

The center also hosts three core laboratories which are available for use by scientists associated with the center as well as researchers and students from outside institutions.

  • The Microfluidics Facility at Princeton University is a shared-use facility for the fabrication, assembly and use of microfluidic chips for cancer, and evolution experiments.
  • The Cell and Tissue Facility at the University of California-San Francisco provides standardized cell lines to all centers in the Physical Sciences-Oncology center network.
  • The Nano-Analysis Shared Resource for Genomic Sequencing at the University of California-Santa Cruz provides equipment and techniques for using sequencing methods to analyze gene expression, DNA methylation states, micro-RNA signatures and gene translocation/duplication in the genome.

Established in 2009, the center is led by Robert Austin, a professor of physics at Princeton University. According to Austin, "Cancer remains a persistent and fundamental problem to human health for basically 3 reasons:  (1) We certainly know ways to cut in half the cancer rate tomorrow (remove smoking and obesity) but the prospects for that happening given our political will power are basically zero, which is tragic. (2) We do not have a deep understanding of the origins of cancer: why has it not been selected out by evolution, how does it begin, how does it progress? (3) Our present main treatment of cancer, chemotherapy, is probably doomed to failure because we do not understand the origins of resistance.  The Princeton Physical Science Oncology Center can do nothing about (1), but is trying to make fundamental inroads on (2) and (3)."