Some long-lived vertebrates are naturally resistant to developing tumors, but why this is so is not completely understood. Scientists hope to uncover more about natural mechanisms of tumor resistance in animals in order to help fight human cancers.
Stem-cell biologist Jun Wu joined the faculty of The University of Texas Southwestern Medical Center Department of Molecular Biology. He was recruited in 2018 from the Salk Institute in San Diego with the help of a First-Time Tenure-Track Award from CPRIT.
Most cancer research using animals focuses on a few species, like rats and mice, that tend to have a high incidence of tumor formation. Wu hopes to gain clues about cancer suppression, which must have played a role in the evolution of long-lived species. He plans to study the natural tumor-resistance of naked mole-rats, which live ten times longer than rats and mice and rarely ever develop cancer.
Because naked mole-rats are difficult to work with as research animals, Wu is using a novel technique to create a chimeric animal, part mouse and part naked mole-rat. He hopes to mix stem cells obtained from naked mole-rats with a mouse embryo, so that as it develops, the resulting animal contains parts of each species.
He’s already used this technique in the past to create part-mouse, part-rat chimeras, which contain cells of both species throughout their bodies. He has even demonstrated that by using modern gene-editing techniques, he can direct the cells to produce certain organs, such as a mouse pancreas inside a rat, or vice versa, for example.
Creating the mouse–naked-mole-rat chimera is more challenging, however, because the two species are evolutionarily very distant. First, he’ll study cultured cells of each species and see how the cells from the different species cross-talk with one another. After these studies succeed, he’ll create the naked mole-rat chimeras.
Using the gene-editing technique to create a liver made up of naked mole-rat cells will allow Wu see if tumor resistance conferred by the naked mole-rat is preserved in the matrix of tumor-susceptible mouse cells.
“We can use this system to study the cross-talk between the two species and see if the cancer resistance is still conserved,” he says. “We hope to understand it better so we can develop screening for chemicals and drugs mimicking the cancer resistance of naked mole-rat cells, and eventually use this to help humans.”
Wu is grateful for the support from CPRIT, because it gives him a lot of freedom as well as the financial support necessary to work with stem cells and animals. “Many other funding agencies would have considered this a very risky project, and wouldn’t have funded it,” he says, “but my work looks at this question of tumor resistance from a very different angle, and it could lead to future breakthroughs.”
Wu studied clinical medicine at Shandong University Medical School in China before embarking on graduate studies in genome science at the University of Tennessee and Oak Ridge National Laboratory, where he received his Ph.D. He was a postdoctoral fellow in stem cell and regenerative medicine at the University of Southern California Keck School of Medicine before joining the Salk Institute as a research associate in 2012. He became a staff scientist there in 2016.
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