How Does A Normal Cell Become A Cancer Cell?

EVANSTON, Ill. --- Northwestern University has received a five-year, $9.6 million grant from the National Cancer Institute (NCI) for a new Physical Science-Oncology Center that unites physical scientists and cancer researchers from Northwestern, the University of Chicago and University of Illinois at Chicago.

The Chicago Region Physical Science-Oncology Center (CR-PSOC) is part of a larger coalition assembled by the NCI to bring breakthroughs in the physical sciences to bear on the complex problem of cancer. Only four such centers have been funded across the nation this year.

“Cancer patients expect us to increase the speed with which we apply discoveries in the basic sciences to prevention, detection and treatment,” said Northwestern’s Thomas V. O’Halloran, the CR-PSOC’s principal investigator. “The center’s mission is to advance our understanding of cancer by examining the role of physical and chemical forces involved in transforming a normal cell into a cancer-causing cell.”

This is the second PS-OC at Northwestern. The first center, under the leadership of the late Jonathan Widom and Dr. Jonathan D. Licht, was funded in 2009 for five years. That innovative work led to the CR-PSOC’s expanded research scope and interdisciplinary collaborations with researchers across Chicago and the country.

“The National Cancer Institute expects these centers to stimulate the flow of new ideas, diagnostic methods and therapeutic approaches between the physical science and cancer research communities,” said O’Halloran, the Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences.

O’Halloran, a physical scientist, and Licht, a cancer researcher and the Dobe Professor of Hematology-Oncology at Northwestern University Feinberg School of Medicine, will lead the CR-PSOC. Both are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 

“What we’re trying to do is understand the fundamental rules of misbehavior of cancer cells with a particular class of mutations,” Licht said. “The center is reaching beyond genomics into the rapidly growing areas of epigenetics and metallomics.”

Scientists have long known that the transformation of healthy cells to cancer cells involves more than just mutations in our genetic DNA sequence. The CR-PSOC team will develop new ways to interrogate changes in the “epigenome” (the chemical markers that influence the folding and condensation of DNA within the nucleus) and changes in the “metallome” (the metal ion content of the cell) that support the development of cancer.  

The “packaging” of DNA influences the local environment of genes and their regulation, O’Halloran explained. DNA is packaged together with proteins, RNA and metal ions into a structure known as chromatin, which is responsible for DNA folding and plays a vital role in gene expression. 

CR-PSOC investigators will deploy a series of physical science approaches and novel imaging methods to determine whether changes in chromatin folding result in aberrant patterns of gene expression that drive cancer progression. Then, the researchers will translate these advances into a deeper understanding of cancer biology and, eventually, into novel cancer therapy.

The core Chicago-area team is composed of 12 physical scientists and eight cancer researchers from fields including physics, chemistry, biomedical engineering, biophysics, biochemistry, pharmacology and hematology-oncology from Northwestern, UChicago and UIC. 

CR-PSOC project leaders have recruited additional experts in the physical sciences and chromatin fields from outside Chicago, namely from Massachusetts Institute of Technology, Memorial-Sloan Kettering Cancer Center and the University of Massachusetts Medical School.

“Thought leaders in the physical sciences and oncology fields have joined forces to share emergent ideas and cutting-edge methods and use them to understand molecular changes that allow cancer cells to grow out of control,” O’Halloran said. “By combining interdisciplinary strengths, this team hopes to make significant progress in the diagnosis and treatment of several types of cancer.”

Designed around the theme of “Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer,” the center consists of three interrelated project areas, each focused on different aspects of chromatin structure and function, plus two core facilities and pilot project, education and outreach programs. 

The center will be a knowledge hub for training the next generations of scholars to make breakthroughs at the convergence of physical sciences and oncology. Center programming will include an extensive series of workshops, student forums, symposia and journal clubs.  An institutional commitment by Northwestern to support the training of graduate students and postdoctoral fellows engaged in CR-PSOC research will further extend the center’s educational reach.

The CR-PSOC is supported by the resources and expertise of Northwestern’s foremost engines for transdisciplinary research, the Chemistry of Life Processes Institute and the Lurie Cancer Center, as well as by resources of UChicago and UIC.

In addition, a Chicago Biomedical Consortium (CBC) Lever Award of $1.5 million will support the center and its acquisition of new instrumentation and shared resources. These research capabilities also will be available to researchers across the region.

A full list of CR-PSOC investigators can be found on the center’s website.