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Professor, Students Search for New Ways to Diagnose Ovarian Cancer

When Rebecca Whelan stumbled across an article on ovarian cancer, she was shocked to discover that the survival rate for 70 percent of the women diagnosed with the disease was only 15 to 20 percent. The article motivated Whelan to begin searching for new, noninvasive ways to detect the disease in its earliest stages, thereby improving the outcome of women diagnosed with the deadly cancer.  

"Because the initial symptoms are very subtle, the majority of women with ovarian cancer aren't diagnosed until the disease has reached stage III and spread from their ovaries to their upper abdomen," says Whelan, an assistant professor of chemistry. "If we can find a way to detect this cancer before it spreads, more women will be able to call themselves survivors."

Whelan, who refers to herself as a bio-analytical chemist, has focused her research on CA 125, a protein that is often found in higher-than-normal amounts in the blood of women with ovarian cancer and is widely used as a biomarker to diagnose the disease. She is spending the summer months in her lab with four student assistants, searching for new ways to identify the protein molecule in blood samples and making the identification process quicker, cheaper, and more reliable than the blood tests or surgical procedures used by scientists today.

Helping Whelan in the lab are Anita Ofori-Addo '06, Nolan Pearson '07, Emily Magorian '08, and Matthew Thayer '08. Each student is experimenting with a different technique--techniques that may one day be used to screen all women for ovarian cancer, just like doctors use mammograms to test women for breast cancer today.

"The detection methods we are working on combine tools from the fields of analytical chemistry and molecular biology," Whelan says. "They also take advantage of the fact that certain biomolecules have the ability to recognize and bind to specific biomolecules while ignoring all others, which can help us identify the biomarker protein in serum or blood samples."

Whelan is taking a two-pronged approach to her searching for a way to detect CA 125 in a blood sample: she is using an antibody that recognizes the biomarker, and she is experimenting with aptamers, modified nucleic acid molecules, as a way to detect CA 125. Both methods exploit the ability of the antibody or aptamer to "see" CA 125 and ignore other nearby molecules.

Thayer, a biochemistry and biology major, is using a small device known as a Spreeta to detect CA 125 in blood samples. The device uses a process called surface plasmon resonance (SPR) to recognize CA 125 molecules by measuring the refractive index of very thin layers of material absorbed onto a metal surface. Although the Spreeta was not originally designed for this purpose, Whelan and Thayer are confident that it could become one of the first hand-held and relatively inexpensive devices used to identify biomarker molecules in blood samples.

"I never expected to learn as much as I have already learned, and have yet to learn, this summer," says Thayer. "The techniques I'm using in the lab are completely new to me, and I've had to do a lot of reading to acquaint myself with them."   

But Whelan is hedging her bets and experimenting with a second method, called capillary electrophoresis, to test for the presence of CA 125 in blood samples. Pearson, a biochemistry and piano performance major, is helping Whelan with this project, which involves using an electric field to separate molecules from each other in a glass capillary tube. As the molecules drift to different sides of the tube, Pearson will introduce an antibody that is attracted to CA 125. This antibody, which is labeled with a fluorescent dye, will help Whelan and Pearson detect the cancer biomarker in individual blood samples.

"I'm interested in research with potential medical applications, so I knew that this project would be a good match for me," Pearson says. "Plus, I was attracted to the exciting, maybe even optimistic, big-picture application of the group's work as a whole."

While antibodies are one way to detect CA 125, aptamers present a more flexible and less expensive option. Unlike a naturally occurring antibody or antigen, aptamers are sytnthetic DNA or RNA molecules that can bind to a particular target molecule, such as CA 125. But unlike antibodies, aptamers are easier to obtain and can be used over and over again, under extreme conditions. Ofori-Addo and Magorian, both biochemistry majors, are making aptamers using a process known as SELEX -- or Systematic Evolution of Ligands by Exponential Enrichment -- which involves testing a random pool of DNA to see which aptamer will grab onto CA 125 and then duplicating it for future experiments.

"I hope that with a little tweaking, the work we do this summer will allow doctors to diagnose and treat a variety of disorders," says Magorian. "I think I could easily become addicted to developing better methods of helping people overcome disease."

After agreeing with her lab-mate, Ofori Addo adds: "As a pre-med student, I'm glad that the work I'm doing in Professor Whelan's lab will help make the early detection of ovarian cancer possible. I have no doubt that this research experience will prepare me to become a good doctor in the future."

Whelan acknowledges that much of her research is still experimental, but the goal is worth the effort.

"Anything that can help us avoid major surgery as a way to diagnose ovarian cancer is going to be easier, and healthier, for women in the long run," Whelan says. "If we can improve these techniques, biomarker screening will become a simple routine test that doctors can perform to diagnose this disease before it becomes a death sentence for a woman."

Whelan's research is supported by grants from the Camille and Henry Dreyfus
Foundation and the Society for Analytical Chemists (Pittsburgh).
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From left to right: Rebecca Whelan, Nolan Pearson '07, Emily Magorian '08, and Matthew Thayer '08

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