An innovative cancer imaging center at Washington University School of Medicine in St. Louis has received a five-year, $10 million grant from the National Cancer Institute (NCI).
The grant will fund a second cycle of research at the Washington University Molecular Imaging Center, where scientists from many different specialties collaborate on advanced imaging projects. Initiatives at the center include an effort to help researchers track the spread of gene therapy for cancer and projects to closely monitor the contributions of key genes to the start of tumors.
“A number of research projects from the first grant have led to technology and approaches to imaging that we’re now leveraging to answer major biological questions in this second grant,” says the Center’s director, David Piwnica-Worms, M.D., Ph.D., professor of radiology and of molecular biology and pharmacology.
Piwnica-Worms is a co-investigator on a Molecular Imaging Center project led by John F. DiPersio, M.D., Ph.D., the Lewis T. and Rosalind B. Apple Professor of Medicine. DiPersio treats difficult cases of leukemia, lymphoma and other cancers with bone marrow transplants. The transplants sometimes lead to a potentially fatal complication called graft-versus-host disease (GVH), where the transplanted cells begin to attack the patient. As a failsafe against this serious complication, DiPersio has developed a way of incorporating a “suicide gene” that can cause the transplanted cells to self-destruct. Scientists activate the gene by giving patients a drug.
Using radiolabeled tracers developed at the Molecular Imaging Center, scientists can now track where cells from the bone marrow transplants go in the body through whole body imaging with positron emission tomography (PET).
“We know from mouse models that there are some different patterns of cell trafficking that seem to predict GVH,” Piwnica-Worms says. “Obviously, we can’t currently make human treatment decisions based on these kinds of patterns. But we’ll be looking for potential correlations with an eye to maybe one day determining by PET that GVH is starting even before clinical symptoms become apparent.”
In another project, researchers led by Lee Ratner, M.D., Ph.D., professor of molecular microbiology and of medicine, will use a genetically engineered mouse line to study the roots of tumor formation. The mice have a mutated copy of a gene called Tax that is linked to the formation of cancers. In a research project during the Molecular Imaging Center’s first five years, scientists added the genetic coding for a luminescent protein from fireflies to the mutated Tax gene. Now when the mice develop tumors linked to Tax, the tumors will glow. Researchers can detect this glow through non-invasive imaging of live mice, giving them an important chance to study tumor development at its earliest stages.
Scientists led by Helen Piwnica-Worms, Ph.D., professor of cell biology and physiology and of medicine, will probe cells’ progression through the various stages of their life cycles. Piwnica-Worms and her colleagues are using molecular imaging to better understand how delays in the processes of replication are created, allowing cells to inspect their own DNA for damage that could lead to cancer.
Raphael Kopan, Ph.D., professor of molecular biology and pharmacology and of medicine, leads a fourth project that will examine how a protein called Notch contributes to cancer. Kopan’s effort will harness one of the Molecular Imaging Center’s core facilities, which make available technology, equipment and expertise commonly needed for research. This project will make use of a high-throughput screening core that allows rapid testing of compounds for desirable interactions with a target molecule. Kopan’s group wants to identify potential pharmaceutical treatments that prevent Notch from helping cancers.
The Center’s other core facilities include a chemistry core that helps develop optical probes and imaging agents for new biological targets; and a molecular imaging reporter core, which contains tools for genetically altering cells and animals to enable tracking of molecules of interest.
“It’s an NCI-funded program, so our core focus is cancer, but the center’s resources also support collaborative imaging efforts in a wide variety of fields including immunology, neuroscience and cardiovascular disease,” notes Piwnica-Worms.
In addition to research activities, the Center’s new grant includes funding for support of postdoctoral and graduate students.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.