When Insight Meets Imagination

Pelotonia funds help bright ideas become breakthroughs

BY DARRELL E. WARD

“Brilliant ideas can lead to extraordinary breakthroughs, but without data to back them up, they have little chance of being funded or of the breakthroughs ever seeing the light of day,” says Michael A. Caligiuri, MD, director of Ohio State’s Comprehensive Cancer Center and CEO of The James Cancer Hospital and Solove Research Institute.

The Pelotonia Idea Grant program gives life to such high-risk, high-reward research by teams of OSUCCC – James investigators.

“Pelotonia Idea Grants provide seed funding for ideas that can lead to critical preliminary data, new collaborations, and ultimately discovery – which can in turn lead to breakthroughs in science, prevention and treatments, and to larger grants,” Caligiuri says.

Applications for Idea Grants, which provide $100,000 over two years, are judged using a peer-review process that considers a study’s potential for discovery, publication, clinical trials, patients and leverage for subsequent funding from the National Cancer Institute. Applicants also must provide a “commitment to ridership” to ensure that they will participate in Pelotonia to help raise money for cancer research at the OSUCCC – James.

The first Pelotonia Idea Grants, 10 in all, were awarded in 2010 using a portion of the $4.5 million raised during the inaugural Pelotonia cycling tour the previous year. Two examples of the innovative ideas funded by Pelotonia Idea Grants are provided below; the remaining eight projects are listed in the sidebar.

Imaging Precancerous Pancreatic Lesions


Pancreatic cancer is nearly universally fatal, and effective ways to detect it early and prevent the disease are needed. Recent research has identified precancerous abnormalities in the pancreatic duct that might help identify people at risk, but current imaging methods are unable to detect these abnormalities.

A team of OSUCCC – James researchers is working to solve the problem by adapting an experimental imaging technology called Optical Coherence Tomography (OCT), which might detect these precancerous lesions.

Mark Bloomston, MD, a surgeon specializing in gastrointestinal oncology and a member of the OSUCCC – James Molecular Biology and Cancer Genetics Program; Wendy Frankel, MD, a pathologist and member of the cancer center’s Innate Immunity Program; and Lanchun Lu, PhD, assistant professor of Radiation Oncology at the OSUCCC – James, make up the Ohio State team. They are collaborating with Zhilin Hu, PhD, a researcher in Biomedical Engineering at Washington University, who developed the technology.

OCT can image the lining of the pancreatic duct at the cellular level. The device uses a fiber-sized probe that can be inserted non-invasively into the pancreatic duct to provide 3-D images. This reveals abnormal cells that would not be detectable using current imaging technology.

The researchers will use OCT in the operating room to image the duct after the pancreas has been removed from patients with suspected precancerous lesions. They will confirm the findings with histological examinations.

“We expect to detect occult cancers in six to eight of the 30 to 40 patients we estimate will have this surgery at Ohio State over the two years of the project,” Bloomston
says.

If the OCT proves reliable, Bloomston and his colleagues will undertake a larger project to image prior to surgery the pancreas of patients at high risk for pancreatic cancer.

The OCT device also is designed to deliver radiation therapy, potentially enabling the treatment of precancerous lesions without the need for radical surgery.

“Such an advance could revolutionize the early detection and prevention of pancreatic cancer,” Bloomston says.

Developing a Rational Therapy for Neurofibromatosis


Neurofibromatosis type 1 (NF1) is an inherited, autosomal-dominant disorder that causes nerve tissue to produce tumors, which sometimes become malignant. The condition affects Schwann cells, melanocytes and endoneural fibroblasts. Tumors can develop throughout the body and cause problems by compressing peripheral and spinal nerves, and by affecting bones and other tissues. Affected melanocytes cause skin discolorations called café au lait spots.

The molecular cause of NF1 is poorly understood. Research by Jianqiang Wu, MD, a researcher with the OSUCCC – James Experimental Therapeutics Program, and James Fuchs, PhD, assistant professor of Medicinal Chemistry and Pharmacognosy in Ohio State’s College of Pharmacy, has shown that the gene called STAT3 is constitutively activated in Schwann cells.

The investigators hypothesize that STAT3 activation in Schwann cells and their precursors contributes to NF1 development, and that STAT3 activity is stimulated by epidermal growth factor receptor, interleukin-6 or both.

The study has several key components:

Investigate whether targeted deletion of STAT3 in Schwann cells or their precursors will decrease or eliminate neurofibroma formation in an NF1 mouse model. Related to this, they will determine the mechanism(s) of STAT3 in nerve disruption and NF formation.

Test the effect of a novel STAT3 inhibitor, a curcumin analog developed by OSUCCC – James investigators in Ohio State’s College of Pharmacy, on tumor development in the NF1 mouse model.

Define the upstream pathways that activate STAT3 during NF1 development and determine the role played by interleukin-6 in regulating STAT3 activity.

“Our long-term goal is to identify the STAT3 pathways involved in neurofibroma formation and to learn if blocking specific pathways could be a potential treatment strategy,” Wu says. Based on their preliminary data, Wu and Fuchs have already received a grant from the U.S. Department of Defense to pursue this research further.

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