In Fight Vs. Cancer Little Models Lead To Large Breakthroughs


Thousands of zebrafish serve as models for Maura McGrail’s cancer-fighting research. McGrail studies the development of glioma, a brain cancer in humans.

Inch-long zebrafish are used as a model organism by several Iowa State researchers. McGrail, an assistant professor in genetics, development and cell biology, is studying them for a project to understand the development of glioma, a brain cancer in humans.

She says an advantage to using zebrafish it is that her team can do genetic research on a large scale at a relatively low cost unlike using mice, a prime cancer-research model that is expensive to raise.

“The same genes that work in humans and mice, and other mammals, are functioning in fish as well. We’re trying to understand how the disruption of networks of genes called conserved pathways contributes to carcinogenesis,” she says.

The pathways altered by cancer are normally required for an organism to grow and develop. Understanding these networks during the organism’s development gives scientists insight into what is happening when cancer occurs.

“In cancer research we are trying to figure out what changes in DNA lead to cells growing in an uncontrolled fashion,” McGrail says, “Having large populations of affected individuals, in our case fish, allows us to use genetics to find those changes in the DNA.”

The zebrafish are providing insight into the genes that could be functioning in the development of glioma, a brain cancer, in humans. Previous work developed a genetic system that identified genes involved in carcinoma and sarcoma.

The system used transposons, pieces of DNA that move around the genome and cause mutations when they insert into genes. Examining where the transposons landed in the zebrafish tumors revealed genes involved in DNA repair and cell growth that are also mutated in human cancer.

McGrail’s present project will take that system for cancer gene identification and use it to specifically look for new genes that promote glioma formation and progression. If the transposon “hits” the same gene over and over again in tumors from many different fish, this provides evidence that the gene is involved in cancer.

In addition to fish care, student researchers in her lab carry out independent projects to study how genes are involved in brain development and cancer. (Read more about one such project by Crystal Jones-Sotomayor on page 10.)

The prognosis of those with malignant glioma is poor, she says. Surgery is an option, but can result in damage to surrounding brain tissue. Understanding how genes work together in advancing disease will provide insights into potential targets for new therapies. The Roy J. Carver Charitable Trust and the National Institutes of Health/National Cancer Institute are funding the research.

McGrail’s husband Jeff Essner also works with zebrafish, researching how blood vessels grow. “Our research programs dovetail quite a bit. Understanding the role of blood vessels and tumor growth is very important for developing cancer therapies. We take two different approaches to the same question,” she says.