Understanding what makes cancer cells become invasive and spread throughout the body—the process known as metastasis—is one of the “holy grails” of cancer research. A better understanding of how cells metastasize could lead to new therapeutic targets for treating cancer.
Computational cell biologist Gaudenz Danuser, Inaugural Chair of the Department of Bioinformatics at the University of Texas Southwestern Medical Center, is using cutting-edge microscopy to look at the inner workings of cells in real time. He hopes to better understand how genetic mutations affect the cell machinery that turns a cancer cell into a mobile weapon.
Danuser was recruited to the University of Texas Southwestern Medical Center from Harvard Medical School in 2013, with the help of a CPRIT Established Investigator Award. He founded an interdisciplinary laboratory of researchers, including cell biologists, biophysicists, mathematicians, computer scientists, and even medical students. In 2016 his laboratory comprised 25 people, including faculty, staff, postdoctoral fellows, and graduate students.
“In metastasis, a cancer cell needs to migrate but above all it needs to survive in many different environments,” he says. “The cell has almost infinitely much time before it begins to metastasize. The distinction from an ordinary cell is its survival capacity.”
Danuser is using microscopes to map the molecular activities inside cancer cells. Typically, studying a cancer cell under a microscope requires removing it from its context. But as soon as the cell is in a new environment, it behaves differently. “But we’re interested in studying how cancer cells signal, so that’s no good,” Danuser says.
Instead, he creates a three-dimensional artificial-tissue environment so that he can study cancer cells in a more natural context. But doing so requires high-resolution and very quantitative microscopy. These instruments generate incredible amounts of data, more than any human could ever analyze, so his lab relies heavily on computational analysis.
His microscopes allowed him to see unusual structures on the surface of a cancer cell, dubbed “blebs” and “spikes.” His lab now hypothesizes that these structures concentrate pro-survival signals, which are more diffuse in normal cells.
He likens it to the coffee a person needs to wake up in the morning. “Coffee spread out all over your countertop isn’t going to help wake you up,” he says. “But coffee concentrated in a coffee cup, now that’s going to do something.”
Danuser says the investment by CPRIT enabled him to expand his laboratory far beyond what he was able to do at Harvard. “Starting such a research program required an initial investment that was impossible for me to get as a full professor at Harvard,” he said. And as a consequence, at UT Southwestern, “I have, intellectually, the best lab that I have ever had in my life.”
He and his associates have attracted research funding from the National Institutes of Health, the total of which by 2019 will exceed the initial investment by CPRIT.
Danuser received his undergraduate and graduate training at ETH Zurich, in Switzerland, receiving a Ph.D. in electrical engineering. He headed a laboratory at the Scripps Research Institute in La Jolla, Calif., prior to joining the faculty at Harvard Medical School in 2009.
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