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July 2010 Issue
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Yana Zavros, PhD, with graduate students Jessica Donnelly (left) and Chang Xiao (right), was awarded $720,000 from the American Cancer Society for her research into the causes of gastric cancer.
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'Sonic Hedgehog' Much More Than a Game for This Team

By Keith Herrell
Published July 2010

It sounds like something out of a high school science geek’s imagination: a deadly disease, a protein named after a video game character and a researcher armed with fresh financial resources.

It’s not imaginary in UC’s molecular and cellular physiology department, where assistant professor Yana Zavros, PhD, is investigating gastric cancer and how biological changes to the cells lining the stomach promote tumor initiation and growth.

Zavros was awarded a $720,000 grant from the American Cancer Society for a four-year period 
that began this month to support her work, which involves studying how chronic infection with the bacterium Helicobacter pylori leads to gastric cancer (also known as stomach cancer).

The society awarded a similar grant to Cincinnati Children’s Hospital Medical Center researcher and UC assisant professor Kathryn Wikenheiser-Brokamp, MD, PhD, to aid in her study of the retinoblastoma protein family’s role in the development of cancerous lung tissue.

Zavros’ study of gastric cancer also involves the role of a protein known as Sonic Hedgehog, named after the video game character "Sonic the Hedgehog” by its discoverers in 1995. Sonic Hedgehog is highly expressed in the adult stomach, and its loss via inflammation or disease contributes to molecular changes that are crucial to development of gastric cancer.

In 2009, there were an estimated 21,130 new cases of stomach cancer in the United States, according to the National Cancer Institute of the National Institutes of Health (NIH). U.S. deaths from stomach cancer totaled 10,620 annually.

Zavros’ lab—which includes graduate students Chang Xiao and Jessica Donnelly—has developed a mouse model to aid in the study of gastric cancer, knocking out Sonic Hedgehog in a single cell type where it was predominantly ex-pressed. With the Sonic Hedge-hog knocked out, researchers in the lab can more effectively study the development of gastric cancer.

An article published earlier this year from Zavros’ lab reported new findings showing the complex regulation of cell growth and differentiation within the stomach and how this regulation can be disrupted during the development of gastric cancer. The article appeared in the February 2010  issue of Gastroenterology, the official journal of the AGA (American Gastroenterological Association) Institute. 

The article was selected and evaluated for Faculty of 1000 Medicine, an online literature awareness service that evaluates the most important articles in medicine based on the recommendations of a faculty of peer-nominated researchers and clinicians.

"I think people are excited that there is now a model that actually looks at the direct role of Sonic Hedgehog in the stomach,” says Zavros. 

"Previously, it was very correlative—people just assumed that with inflammation you lose Sonic Hedgehog and this is what triggers the cascade of events that eventually lead to gastric cancer.”

Zavros says her lab’s long-term goal is to understand the mechanism by which inflammation triggers the development of gastric cancer.


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