In Residence

The Topic of Cancer

By Cory MacPherson
Vital Signs » Summer 2011
Photo of Rebecca Tuttle, M.D.

Surgery resident's passion for research leads to new insights into possible treatments for cancer

A cure for cancer.

It’s almost a cliché, like saying you want world peace at a beauty pageant. Yet it is a very real goal for many researchers who work tirelessly to stop this disease, which accounts for nearly one in four deaths in the United States.

One of those researchers is Rebecca Tuttle, M.D., a third-year resident in the Boonshoft School of Medicine Department of Surgery. Together with Wright State professor Steven Berberich, Ph.D., chair of biochemistry and molecular biology, Tuttle has studied a gene that could play a role in stopping the growth of cancerous tumors.

Doctor since diapers
Growing up with two physicians as parents, Tuttle was always fascinated by the science of the human body. She knew from an early age that she wanted to become a doctor herself.

The body is amazing in general, she said. She chose surgery as a specialty because “you really get to see the body’s intricate workings.”

Tuttle earned her bachelor’s in chemistry at the University of Toledo and her medical degree from the University of Cincinnati before coming to Wright State for her surgical residency.

“I liked Wright State because all the faculty here are very approachable,” said Tuttle. “They are thankful for your efforts and supportive of your learning. They advocate for your best interest.”

Knowing early on that she wanted to pursue research, she took advantage of the research option offered by the Boonshoft School of Medicine. Residents here can choose to take two years off after their second clinical year to pursue medical research.

She spoke to Robert Fyffe, Ph.D., university professor, associate dean for research affairs and professor of neuroscience, cell biology and physiology in the Boonshoft School of Medicine, about her desire to do cancer research. He directed her to Berberich’s lab, which was already making cancer-related discoveries.

Yippee for cancer research
Berberich and his research team were studying a gene called Yippee like-3 (YPEL3). They had already discovered that YPEL3 was directly activated by the p53 tumor suppressor proteins, and that activating YPEL3 triggered cellular senescence, causing cells to stop dividing.

This means that elevating YPEL3 could potentially stop cancer cells from multiplying and stop tumors from growing.

Berberich had been studying the gene from a basic science perspective, but Tuttle joined the lab with an interest in translating those findings into clinical cancer scenarios.

Together, Tuttle and Berberich looked at whether or not YPEL3 is down-regulated in human cancers and whether or not cancer cells are able to grow because the gene is inactivated.

“We were extremely fortunate,” said Berberich. “Although Becky didn’t have any previous cell biology research experience, her work ethic was phenomenal. She mastered the techniques with ease and was very talented in her ability to grasp the science.”

Tuttle joined the laboratory just as the growth inhibitory effects of YPEL3 were being uncovered. She was a co-author on the initial 2010 publication in Cancer Research detailing YPEL3 as a p53 activated gene.

From there Tuttle engaged surgeons from the Dayton region in the project to address whether YPEL3 gene expression was lost in human cancers. Based on her preliminary study screening of eight human tumor types, Tuttle focused on colon cancers.

In January 2010, Tuttle and Berberich, with several medical school surgeons, reported in the Annals of Surgical Oncology that colon tumors show a decrease in YPEL3 expression.

Berberich gives much of the credit for their success to Tuttle.

“Her work really elevated this project,” he said. “It went from simply a gene that we thought was activated by p53 to really current belief that the YPEL3 protein represents a new target that can impact cell growth.”

This YPEL3 research could one day lead to a treatment that would stop cancer in its tracks. Since the gene expression appears to be low in some human tumors, doctors could try to therapeutically reactivate the gene to halt a tumor’s growth. Once the cancerous cells stop dividing, the body can remove them.

Not all human tumors lose the YPEL3 gene, said Berberich. But in those that do, a good treatment may be able to fix the problem. However, it could be years or even decades before a functional treatment could be ready for public use.

“We’re trying to understand what makes cancer cancer, and that’s difficult because every patient and every tumor is different,” said Tuttle.

Life after the lab
During her two years in Berberich’s lab, Tuttle found that she had a real passion for research.

“I missed surgery while I was doing the research, but I loved the creativity,” she said. “It’s very different being in the lab versus working with patients. You have a lot more leeway, and there are fewer consequences when something doesn’t work. You simply tweak the experiment and try again. You have the freedom to try anything you can think of.”

Tuttle plans to finish her residency and become a breast surgeon. She knows that her research experience will help her land a more competitive fellowship spot.

It also taught her skills like grant writing and lab management that will one day help her fulfill another dream: opening her own breast cancer research laboratory. Her ideal career would be divided equally between surgery and research.

Still, life in Berberich’s lab lingers in her thoughts. “Steve and I became very good friends,” she said. “We’ve stayed in contact through email and often discuss our research. I know we’ll continue to collaborate in the future.” VS

Last edited on 09/22/2015.