Senior biology major Ashley Leubner—who is pursing a concentration in biomedical studies—wants to be a physician.

That’s why she conducted Field Periods with different physicians in the Hornell area (her hometown is Greenwood, SteubenCounty) during her first three Field Periods.

Her final Field Period—conducted over the summer—was different. Leubener traveled to Louisville, Ky., where she spent 10 weeks in Carolyn Klinge’s ’79 lab at the University of Louisville.

“I looked at breast cancer lines, the drug Tamoxifen (used to treat breast cancer), and drug resistance in breast cancer,” said Leubner.

“Cancer is a disease of misbehaving cells; cancer cells divide at a greater rate than they should and form tumors,” Professor of Biology Joan Magnusen explained. “Misbehaving is an apt description because what cancer cells do is stop responding to the normal signals that tell cells to divide at a rate that replaces lost cells. Cancer cells divide without signals or at a greater rate than the signals would normally determine. Scientists try to understand what molecular changes cause this deafness to normal signals and develop drugs to counteract the misbehavior. Tamoxifen (TAM) is an anti-cancer drug that is used to treat breast cancer by stopping cell division. Unfortunately, some breast cancer cells develop resistance to TAM; they divide even when TAM is present.” 

“The cancer responds to the Tamoxifen at first, but then Tamoxifen resistant tumors form,” explained Leubener, who worked in a Laminar Flowhood (pictured) to keep the cells from becoming contaminated. She treated the cells with antiestrogen “to see what it does on a molecular level.”

“Dr. Klinge’s lab is trying to understand how some breast cancer cells manage to ignore the stop signal from TAM and divide,” said Magnusen. “This knowledge might suggest other drugs to stop the division of TAM-resistant breast cancer cells or help physicians recognize breast cancers that won’t continue to respond to TAM. This summer, Ashley investigated one strategy that cancer cells might be using to overcome the stop signal from TAM. They might turn off the DNA that makes another protein needed to block cell division.”

Leubner performed a series of experiments that compared cultured breast cancer cells that are and are not responsive to the stop signal from Tamoxifen.

“I used [laboratory techniques] such as Western blot (to look at proteins) and quantitative tool Q-RT-PCR, which I learned about in classes with Dr. Magnusen,” said Leubner. “It was nice to put them to practical use and tie it all together.”

Though the physical component of her research ended at the conclusion of her Field Period, Leubner continued analyzing her research during the fall semester.

“It didn’t necessarily make sense to me while I was there,” said Leubner.

However, with the help and guidance of adviser Magnusen, Leubner was able to derive conclusions from her research.

“We were ultimately trying to determine how protein COUP-TFII is regulated in Tamoxifen-sensitive and -resistant cell lines,” said Leubner, whose work supported the hypothesis that Tamoxifen resistance might be a result of changes at the DNA level.

Leubner presented her conclusions to the Division of Natural Sciences, Mathematics, and Physical Education Dec. 5 to apply for divisional honors, which she was granted. She is also a member of Chi Beta Phi, a national honorary scientific fraternity whose purpose is to promote interest in science.

-- Tanya Cornell-Kestler