FEATURES • Spring 2001

Using the wellspring of her imagination, Professor Karen Wooley is researching new ways to use synthetic polymers. She and her research team are perfecting molecular carriers called "knedels" by hollowing out their interiors—designing them to deliver drugs or withdraw cholesterol from blood.

By Jeanne Erdmann

Chemistry Professor Karen Wooley runs her hand across a green plastic pillow filled with polystyrene beads. The dry winter day charges the air with static electricity causing the beads that are stuck to the pillow lining to fall away under Wooley's moving hand. Although the world of polymer chemistry may seem impossibly complicated to most of us, Wooley shows students and visitors that even the concept of charged pieces of plastic can spark the imagination.

Yet Wooley's imagination stretches well beyond clever teaching aids. Rather than seek a comfortable niche, she prefers forging into new areas of science. First, she gathers data, thinks about a problem, and examines what she sees from different viewpoints—then she plunges forward, never looking back. Her innovative use of polymers—chains of identical molecules—keeps Wooley far ahead of even cutting-edge developments.

"I have this fear or drive or need to not be a follower," says Wooley. "When I see others joining the pack, I run in some other direction."

Wooley has been perfecting a synthetic polymer she created a few years ago. She calls these tiny particles "knedels" because they look like meat-filled Polish dumplings. Like their noodle counterparts, these microscopic particles have a core of one composition surrounded by an outer shell made of something else. Wooley and her team are hollowing out the core so it can eventually be used to deliver drugs. Knedels are the same size as proteins found in nature, and they share many of the same properties found in biological molecules. Although we may not find these knedels appetizing, Wooley has found a way to make them appealing to cells. She attaches protein transduction domains, a special group of molecules that help bring knedels—along with any drug or gene that might be inside—directly into cells. One day, scientists may be able to fill knedels with cancer-killing drugs or even leave them hollow so these tiny cages can scavenge cholesterol from the bloodstream or clean up an environmental hazard.

"The goal of my research team is to design and accurately manipulate materials for a number of very different applications. This is what excites me most about polymer chemistry research. This vision is what motivates me," says Wooley. "For example, slight changes in the chemistry can cause polymers to be fluid or rubbery or brittle. I see chemistry expertise as the ability to control matter at a fundamental level."



Atomic force microscope topographical image of SCK nanospheres on a surface.

Illustration by Chris Clark, graduate chemistry student


Stabilizing Particles

Assembling these tiny particles is similar to building a microscopic machine, but Wooley uses chemical building blocks in place of nuts and bolts. Connecting just the right molecules to make a chemical dumpling is a skill accomplished by many chemists. Holding these dumplings together is an achievement that Wooley alone pioneered. Her insightful experiments, says senior research scientist Edward Remsen, have stabilized the particles so they may be used in a variety of applications.

"Karen is receptive to new thinking and open to people with different experiences. She realizes that having a diverse group of thinkers around her is very stimulating. There are lots of ways to solve a problem. Sometimes you can look at it straight on or look at it from the opposite side. Karen looks at her science from many different angles. She has a broad vision because she sees the big picture and can focus on specific areas that have the greatest impact," says Remsen, who has joined Wooley's research team after many years as an industrial chemist. "She's a terrific person to work with."

As dedicated as Wooley is to research, she is equally committed to teaching. She brings the same shake-it-up attitude to her classes by revamping course work and keeping her students away from the comfortable ruts she herself so mindfully avoids. Wooley also divides her time among a host of graduate students, whom she delights in mentoring. The feeling must be mutual as they have filled Wooley's office with gifts of pictures and statues, many from other continents. When students graduate and achieve success in their own right, Wooley couldn't be happier.

"One of the most exciting aspects of being a faculty member is taking first- or second-year students, giving them a project, and watching them grow and develop. It's like being a parent many times over. You become very connected to the students, and it's very rewarding," says Wooley.

Work First

Wooley grew up in Oregon as, she says, the middle, rebellious child. From an early age, chemistry captivated her imagination. It's easy to imagine Wooley as a young girl with her head bent over a chemistry kit, but that never happened.

"My parents never bought me one. I think it was the deprivation that caused me to go into the field. They weren't science-oriented, and they might have thought I would cause some havoc," she says. Two years of high school chemistry solidified an unwavering devotion to the field. After receiving her bachelor's of science degree in chemistry from Oregon State University and a doctorate in chemistry from Cornell University, she joined Washington University's Department of Chemistry in Arts & Sciences in 1993.

Joseph J.H. Ackerman, the William Greenleaf Eliot Professor of Chemistry and chair of the chemistry department, says Wooley's extraordinary drive together with her ability to conceive new ideas have helped her reach a level of international recognition unusual for a young scientist. "Karen has been a terrific addition to the department. She leaps ahead while others take small steps," says Ackerman. "She is well on her way to becoming a major star in organic materials chemistry."

Indeed, a peek at her résumé shows an impressive list of Young Investigator awards and a slate of lecture invitations from meetings held all over the world. Wooley credits her success to very hard work and a bit of luck. Her drive, she says, comes from her father who worked as a millwright at a lumber company. He never went to high school or college, but he valued education and the opportunities that came from hard work—and he made certain that his children understood those values. Wooley and her two sisters did their homework and cut firewood.

"I still like to mow the grass, rake leaves, and cut trees. My favorite line is 'work first and play second.' I tell that to my three boys all of the time," says Wooley. "I have calluses on my hands."

Wooley never really needed that childhood chemistry kit because the world around her remains an inspiration. She still picks up seashells to see how they're put together. "I'm pathetic to take on a field trip," she says.

Jeanne Erdmann is a free-lance writer based in St. Louis, Missouri.

For more information on Professor Karen Wooley's research, visit: wunmr.wustl.edu/~wooley/index.html.





School of Medicine scientists are working with proteins to get them into any cells so the proteins can go to work.

Scientists looking for new ways to treat cancer have tried for years to get proteins inside of cells. Proteins carry enough molecular information to destroy cancer cells, but they also are too large to slip through cell membranes. Steven Dowdy (below), assistant professor of pathology and immunology in the School of Medicine and a Howard Hughes Medical Institute assistant investigator, compares cells to a 2-story house with a tiny mail slot as the only point of entry. A letter—like many small molecule drugs under development—could slip easily through the slot but may not contain enough information to be really useful.

Dowdy devised a way, essentially, to take apart a computer, slip it through the mail slot—monitor and all—reassemble it on the inside, and then have it work. That computer, like many full-length proteins, would contain more information and power to fight disease than all of the information in a single "letter" could. Like the computer analogy, Dowdy and his colleagues first use a special chemical to unfold proteins. And then they attach so-called protein transduction domains (PTDs), which allow the protein to diffuse into any cell in the body. Once inside, the cell's own machinery refolds the protein so it can go to work.

"We don't know whether any of this will ever go into the clinic; this is very early data that works great in the lab," says Dowdy. "From an experimental point of view, this is an awesome technology. It's too early to say if and when we might go beyond that into potential clinical trials. We're on a two- to five-year plan here."