LeeAnn Swanegan: Putting antibiotic- resistant bacteria to work killing cancer

By Anne Bromley

Stephanie Gross

LeeAnn Swanegan, a fourth-year doctoral student in biochemistry and molecular genetics, is studying how a compound made by antibiotic-resistant bacteria and injected into prostate cancer cells causes the cells to die.

LeeAnn Swanegan's work in health care has ranged from seeing patients with the Australian Royal Flying Doctors Association to researching cell processes in a U.Va. biochemistry lab.

A Missouri native, Swanegan spent part of her senior undergraduate year abroad at the University of Adelaide, helping physicians deliver primary care to Aboriginal people in remote areas accessible only via airplane -- hence the name "flying doctors." She has traded that kind of adventure for another: delving into cancer research. She is investigating a potential new kind of chemotherapy using a compound produced by antibiotic-resistant bacteria that causes cells to die -- only diseased cells, not healthy ones.

"I like the interdisciplinary approach here, the collaboration," said Swanegan, about why she chose U.Va. "This is basic science that is translational research," meaning the science can be readily put to work on a human health problem.

Swanegan, who hopes to complete her Ph.D. by May 2001, works with Dr. Joel Hockensmith, whose lab in the School of Medicine's Department of Biochemistry and Molecular Genetics looks at interactions between DNA and cell proteins. Swanegan's research builds on a discovery made by Rohini Muthusewami, a previous graduate student now working at the University of Colorado. Muthuswami found that some bacteria make an enzyme that changes the common antibiotic, kanamycin, into a compound harmless to the bacteria but surprisingly toxic to a protein found in rapidly dividing mammalian cells. Several patents are pending for using the method of applying the compound to a variety of diseases, including malaria and cancer.

When incubated with prostate cancer cells, the compound, phosphokanamycin, causes the cells to die by inhibiting the action of a protein that acts as "as molecular motor in the nucleus of mammalian cells," said Swanegan, who's also the vice president of the Graduate Biosciences Society at U.Va. Swanegan and her colleagues have injected the compound into mice carrying solid human prostate tumors. The compound affects the solid tumor but not the surrounding normal cells. So far, the modified kanamycin has yielded complete tumor remission in 25 percent of the mice. Researchers don't understand at this point why the compound affects some cells and not others.

"My graduate thesis consists of studying what happens to the cells as they die. In the future we hope to develop this compound into a new chemotherapy that can be used to treat cancer," she said. Currently, the compound is delivered by direct injection into the tumor mass but applications are being developed to treat a wide variety of cancer types. "These studies highlight the importance of basic biochemical research and how it can be employed for therapeutic gain," said Swanegan, who has applied to the National Cancer Center and the National Institutes of Health for a post-doctoral fellowship.

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