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Ergun Kocak, MD, MS

Award Name Davis/Bremer

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Gene Therapy of Plastic Surgical Flap Tissues in a Mouse Xenograft Model to Treat Human Colorectal Tumor Implants

Ergun Kocak, MD, MS, Assistant Professor in the Ohio State University Department of Plastic Surgery, was awarded pilot funding through the Center for Clinical and Translational Science and Richard P. and Marie R. Bremer Medical Research Fund to support his work on gene directed enzyme prodrug therapy. His project, titled “Gene Therapy of Plastic Surgical Flap Tissues in a Mouse Xenograft Model to Treat Human Colorectal Tumor Implants”, has yielded positive results over the past year, and Kocak said that it may translate into a clinical trial within a five year period.

Ultimately, Kocak and his associates, Matthew During, MD, from the Department of Molecular Virology, Immunology, and Medical Genetics, and Katherine Carruthers, an undergraduate student, are working toward the goal of providing localized chemotherapeutics to tumor resection beds through the use of muscle flaps, which are gene modified using adeno-assocaited viral vectors.

“Such gene modification of tissues opens a new direction in the field of plastic surgery; one that deviates from the traditional goal of reconstruction to address potentially therapeutic applications,” Kocak said.

Although previous studies have been published in this area, Kocak’s work is unique thanks to a novel protocol which was developed to improve the localization of gene product expression. This protocol, which utilizes autologous fat grafts as the vehicle for gene delivery, allows for a slower infusion of viral vectors into the surrounding tissue. Months of research using markers, such as green fluorescence protein and luciferase (the gene that makes fireflies light up) have proven that this slower rate of infusion does result in the level of viral localization that would be necessary for a successful gene therapy treatment regimen.

“The cancers that could potentially be treated using this protocol are vast,” Kocak said. “Now, it is just a matter of finding genes and gene products that will result in effective anti-cancer regimens.”

A successful method of gene delivery is not only important in the world of colorectal cancer, but could potentially be significant in many other fields. According to Kocak, now that his team has successfully developed a method for the local expression of these viral vectors, this technology can be applied to a wide range of applications, from wound healing to limiting ischemia related tissue injury. Although this particular study will focus on the cancer applications, Kocak plans to explore other uses for this novel protocol in the next several years.

The next step for the Kocak team is to begin tumor studies. Now that a successful protocol has been established using biological markers, they feel ready to address the main portion of their research, testing their protocol on actual cancer cells in vivo. The team hopes that they will be able to establish subcutaneous tumors in nude mice (mice without immune systems) using human colorectal cancer cells and subsequently use their fat grafting protocol to administer gene directed enzyme prodrug therapy.

“If successful, tumors will significantly shrink in size,” Kocak said. “We will have cured cancer, at least in our model.”

By Becky King, Friday, July 30, 2010

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Acknowledging CTSA grant support in publications

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