Targeting Genes in the Fight Against Cancer

By Carolyn Shea

In his laboratory at the Fred Hutchinson Cancer Research Center in Seattle, Patrick Paddison ’96 works at the heart of a scientific and medical revolution.

His game-changing research is pinpointing the genes that may someday be targeted to destroy malignant glioblastoma cells in the brain.

Glioblastoma is the most common and aggressive brain tumor in humans. It is difficult to treat and often fatal. Nine out of 10 patients diagnosed with the disease—the same type that killed Senator Edward Kennedy in 2009—die within two years, underscoring the need to develop effective treatments.

Patrick Paddison

Patrick Paddison in his laboratory at the Fred Hutchinson Cancer Research Center in Seattle.

Photo by Shauna Bittle ’98

Paddison is a geneticist at the Hutchinson Center, one of the world’s leading cancer research institutes. He heads the Paddison Lab, which has developed innovative tools to study gene function, and investigates the biology of stem cells and cancer through cutting-edge technology based on RNA interference (RNAi). Discovered in 1998, RNAi is a natural cellular process used by different organisms to regulate gene expression. Researchers like Paddison are now using RNAi tools to shut off specific genes to determine which may be involved in diseases. “It’s allowing us to address questions we wouldn’t otherwise be able to address,” he said.

Paddison and his team are focused on understanding RNAi’s role not only in diseased cells, but also normal ones. They’re gaining new insights into the human genome, which could yield potential clinical applications for a wide range of problems, including cancer. Cancer is one of the most promising targets for RNAi-based therapies because it is often caused by overactive genes, which lead to abnormal, uncontrolled cell growth. Blocking the activity of tumor-initiating genes by knocking them out may prove to be a godsend to patients diagnosed with complex diseases like glioblastoma.

Paddison didn’t start out wanting to pursue a career in genetics and cancer research. While growing up in New Orleans, he wasn’t especially interested in science. He said he arrived at Evergreen, “thinking I would become a psychologist.”

In his senior year, however, he altered that plan. “I took a class that really changed my perspective on things: ‘Science of Mind.’ The course, linking neurobiology, biochemistry, cognitive psychology, and philosophy, was “really hardcore science,” a subject he hadn’t previously studied as an undergrad. And it was revelatory. “I fell in love with the biology side of things,” he said,“ and went from thinking about questions of the mind to trying to understand those questions in terms of biology.”

“Evergreen taught me, not necessarily thinking outside the box, but to envision a world without boxes.”

Patrick Paddison ’96

He spent two more years—and three additional summers—at the college, “backfilling requirements for grad school” by taking more science programs, and spending countless hours working in Evergreen faculty Betty Kutter’s bacteriophage lab, where his passion for research was born. It was with Kutter and several others that he published his first paper, in the scientific journal Genetics, on a gene responsible for a particular mutation of the phage virus. Their discovery of this gene solved a decades-old mystery. “We were able find it by sequencing the genome in the bacteriophage, and we did it by hand,” he said. In the days before high-tech, high-speed gene sequencers were invented, the project took six months of painstaking effort.

After zeroing in on science and acquiring the academic background he needed, Paddison became a research technician at the Hutchinson Center, where he worked with Dr. Lee Hartwell, who in 2001 won the Nobel Prize for uncovering the genetics of cell division. At the time, they were using budding yeast cells to identify genes that control whether a cell is dividing normally. Paddison entered the second class of Cold Spring Harbor Laboratory’s Watson School of Biological Sciences in New York, earning his Ph.D. in 2004, and stayed on at the lab as a postdoctoral fellow for another four years. Since then, he has received substantial support for his work in stem-cell and cancer biology, including being named a Pew Scholar in Biomedical Research, a prestigious award given to early career scientists who “display outstanding promise in research relevant to the advancement of human health.” His work has won funding from the National Cancer Institute and the Accelerate Brain Cancer Cure foundation, which invests in research aimed at finding the fastest possible cures for the disease.

Paddison credits Evergreen with setting him on his career path. Besides allowing him the freedom to discover his passion and pursue it intensely, “Evergreen taught me, not necessarily thinking outside the box,” he said, “but to envision a world without boxes.”

At the Hutchinson Center, he finds some similarities with the college. It cultivates an interdisciplinary approach and “the environment is very collaborative,” he said. “In a lot of ways, it feels like Evergreen, which is very collaborative in how people learn.”

Along with research collaborators at the center— including Evergreen interns who’ve helped in his lab—and at other institutions as well, Paddison is playing a pivotal role in pushing scientific knowledge toward the development of a revolutionary class of anti-cancer compounds: molecules engineered to attack cancer cells without harming healthy cells. The goal is to make headway against a lethal disease and offer hope to the patients who ultimately benefit from Paddison’s groundbreaking work.