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Home > ARRA Stories > University of Iowa Basic and Clinical Scientists Collaborate to Study Newly Identified Gene’s Relationship with Cancer
University of Iowa Basic and Clinical Scientists Collaborate to Study Newly Identified Gene’s Relationship with Cancer

By Jenn Laskowski

March 31, 2010

Photo of Marc Wold and Dan Berg

Marc Wold and Dan Berg

Marc Wold, Ph.D., a UI biochemistry professor, studies DNA metabolism in cells from a very basic biology perspective. He has been working on identifying and characterizing a novel gene called RPA4. This gene is only found in primates and affects one of the major cellular proteins required for DNA replication and repair. Wold was surprised when the initial studies of RPA4 suggested that it might be involved in the process of developing cancer.

Wold's studies showed that RPA4 was down regulated in cancer cells and that RPA4 expressing cells may be unable to become highly proliferative cancer cells. He immediately started asking some really important questions. What is the gene's role in regulating a cell's transformation from noncancerous to cancerous? How is the gene's expression regulated? If RPA4 can be turned on, could it possibly stop existing cancers from getting worse?

However, Wold has only worked with cancer at the cellular level and he quickly realized he needed someone to help him think about cancer in terms of tissues and organs. He needed an experienced clinical scientist.

Then he heard about a $50,000 award from an American Recovery and Reinvestment Act-supported CTSA administrative supplement called Looking into Clinical Connections (LINCC) that was awarded to the Institute for Clinical and Translational Science. LINCC is a faculty development program, piloted in the Carver College of Medicine at the University of Iowa, which links together pairs of laboratory and clinical scientists by funding them with pilot awards. Wold is one of five basic scientists who have received LINCC awards. LINCC intends to support ten pairs of clinical and basic scientists during its pilot stage. Advertising for the second round of LINCC awards will begin at the end of spring semester with a summer due date.

Wold did not have a specific partnership in mind, so he shared his ideas with LINCC program directors. "Dan Berg's name was suggested and I looked at some of his papers and thought he was a perfect fit," Wold said.

Dan Berg, M.D., an oncologist in Holden Comprehensive Cancer Center, received an email from Wold shortly thereafter. He was excited about the basic scientist's interesting observations, especially given the potential roles this gene may play in the normal functioning colon and in the development of colon cancer.

Now these LINCC fellows are working together to explore Wold's questions from two different perspectives. They emphasize that finding a cure for cancer via this gene is still very much a dream and they have years of work ahead of them, "But the point is, in order to try and explore this possibility, we need to know more about where the gene is expressed in normal tissues and to understand its expression in both normal and cancerous tissues" Wold said.

Berg said, "If you see the predicted changes then a lot of questions are raised, such as, what changes take place in a normal colon lining that result in a polyp? What happens when a non-cancerous polyp becomes cancerous, and exactly where in the process does it change?"

Berg helps facilitate the project by working with the pathology department and the tissue procurement core to collect tissues from patients who are undergoing surgery for colon cancer. Then he and Wold will analyze this tissue by looking at both normal and cancerous tissues and observing if the gene is or is not expressed, where it is expressed, and how the expressions change as cells go through different processes.

"We are in the very early stages of a classic translational problem. We think we have a novel observation that may be important to the future of understanding disease, but we have a lot of dots to connect and we have to figure out a lot more basic biology," Wold said. These LINCC fellows are confident their preliminary work will give them enough data to seek further external funding in the future.

This article originally appeared on the Institute for Clinical and Translational Science at the University of Iowa website. Reposted with permission.

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