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When Insight Meets Imagination 

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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.

THE EIGHT REMAINING 2010 PELOTONIA IDEA GRANTS

Here are the titles of the remaining 2010 Pelotonia Idea Grants. Information about the projects is available at cancer.osu.edu/research (Fellowships & Post Docs).

• "Microenvironmental influences on AKT1-regulated transcriptome in tumorigenesis"

• "E-health program to reduce obesity in Appalachia"

• "CBL and EGFR in triple negative breast cancers"

• "Genomic analysis of primary tumor lesions as an approach to early chemoprevention"

• "NF-kB inhibition cancer therapy"

• "Chemopreventive effects of strawberries on the modulation of the cigarette smoke-altered transcriptome in human oral mucosa"

• "Understanding resistance mechanisms to MEK inhibitors in BRAF-activated juvenile pilocytic astrocytomas"

• "PD-1 blockade enhance natural killer cell cytotoxicity against multiple myeloma: Determining molecular mechanisms and in vivo efficacy"



A CHANCE TO HELP OTHERS


ANJALI MISHRA, PhD

Pelotonia means many things to many people. For cancer researcher and Pelotonia-rider Anjali Mishra, PhD, it's a chance to help others.

"The first time that I signed up for Pelotonia, I did not fully understand the commitment and dedication needed to raise funds for cancer research," Mishra says. "But the first opening ceremony changed my perception of this grassroots event, which brings together people from all walks of life for one goal: to beat cancer. It was fantastic, exciting."

Mishra has ridden all three Pelotonia events, which have taken her along the back roads of central Ohio. What she hadn't anticipated, however, were the benefits of raising the funds each rider pledges to donate.

"We organized a number of fundraising events, and for me, a foreigner, each one offered an opportunity to interact with local people. Last year, in addition to bake sales, we painted a barn that belonged to the grandparents of a colleague. The money we raised from that went straight toward my fundraising goal."

The first year, Mishra rode the 43-mile route, which she rode again the second year because of an injury. "My biggest Pelotonia challenge was overcoming a fear of biking on hills," she says.

"Last year there were some 4,000 bikers, and I rode 102 miles, which was pretty good…and those hills were really very, very cool! I plan to ride 180 miles this year in Pelotonia 12, for sure," she says.

Mishra is a researcher in the laboratory of Michael A. Caligiuri, MD, director of Ohio State's Comprehensive Cancer Center and CEO of The James Cancer Hospital and Solove Research Institute. She is working to discover new models for the study of highly aggressive leukemias and lymphomas.

"We're trying to identify novel molecular pathways that we can exploit as targets to develop new therapies for these incurable diseases," she says.

Mishra earned her PhD at Hannover Medical School in Germany. She worked in a pediatric clinic where she saw many small children with very aggressive leukemia.

"There was no cure for those kids," she says. "We could prolong their life for a time, but their quality of life was not what it should have been. Those were the patients that affected me most, and when I think about cancer, and when I'm riding in Pelotonia, those kids pop in front of my eyes. That is who I think about."



Those children come to mind, too, when she watches cancer-research funding fall. "As a researcher, I know that our funding is much lower now, which means we cannot do the large experiments that we need to do. We had to do something about it, and this is what's really great about Pelotonia: It brings people together from all walks of life to raise money for cancer research. This is why I'm a proud supporter of Pelotonia and The James, because they are leading a charge against cancer.

"Pelotonia is a fantastic cause," Mishra says. "A hundred percent of the money raised goes to cancer research. The money stays here in Ohio, but the research that the money supports will be available to people suffering from cancer on any continent. That is the great thing about it. This research will go around the globe."


PELOTONIA MEANINGFUL ON MANY LEVELS FOR CLINICIAN RIDER


DONALD MACK

One evening just before Christmas in 1999, Donald Mack, MD, then a family-practice doctor in the small town of Spencerville, Ohio, discovered a lump on his testicle. It was still there next morning, so he had it examined. "I was fortunate; I found the tumor early, while it was still confined to the gland," Mack says.

His treatment involved surgery and radiation therapy. "I'd go for what I called my 'tanning treatment,'" he says. "It sometimes left me a little tired, but it wasn't nearly what most people with cancer experience."

In 2010, Mack relocated his practice in Spencerville and came to work for The Ohio State University. When he interviewed for the position that April, he learned about Pelotonia. "I immediately wanted to do it," he says.

Though it had been awhile since he'd been on a bike, he enjoyed bicycling. Before starting medical school he'd ridden across the United States with a group of cyclists. Yes, he was now 50 years old, but he wanted to tackle the August ride in recognition of the 10th anniversary of his cancer diagnosis. That it was an Ohio State and James Cancer Hospital event gave it added meaning.

He'd left the month of June free, prior to starting his new job at Ohio State in July, and now he could use it for training. "I became very familiar with the Olentangy bike trail," he says. Once he started work, he rode evenings and weekends.

When Pelotonia weekend arrived, he completed the two-day, 180-mile route, the longest of the rides.

Mack has had many encounters with cancer. As a teenager, his maternal grandmother developed breast cancer. Later, as a physician, he provided end-of life care for his paternal grandmother, who died of a brain tumor. He knows first-hand the anxiety experienced by cancer survivors who come to him for care. "With every test you wonder: What if they find something? What will it mean? What will I do?"

Mack rode Pelotonia again in 2011. A family friend had been diagnosed and treated for breast cancer, and on the day of the ride, a woman close to his family was in The James undergoing treatment for acute myeloid leukemia; her brother had been treated there earlier for pharyngeal cancer.

As Mack prepared that morning to ride, the woman's son and husband were there to see him off. "For them to come was really touching," he says. As he rode, he had all these people—friends, family and patients—in mind.
"I'm a slower rider but pretty determined," Mack says. He wore the Pelotonia shirt that identified him as a survivor, and some riders slowed to talk along the way.

"Other survivors had a much more difficult experience than I did," he says. "One was a young man in his mid-20s, my son's age, who was treated for a childhood cancer and still had memories of it. Another had a fairly advanced renal cancer, and he'd had all sorts of treatments, but boy could he pedal. He left me in his dust as he rode off down the way."

As he rides, Mack says, "I'm working to prove to myself that I can overcome the physical challenge." That was especially true in 2011. During a training ride in May, his bike slipped out from under him on wet pavement, leaving him with a cracked helmet, a concussion and a fractured pelvis. He healed well, and his orthopedist said he could ride Pelotonia, "but I'd have to work for it," he says.

He again completed the 180-mile course.

"I think Pelotonia is a significant event for the riders, most of whom are riding for someone with cancer, and that is multiplied by the good will that comes from raising money to fight cancer and support cancer research at Ohio State's cancer center and The James Cancer Hospital," he says.

Cancer research is vital, he adds. "In 25 years, I've seen so many changes in how we treat cancer. We are making strides every day."

In addition, he says, "Pelotonia raises awareness and draws support for families that are battling cancer or have lost a loved one or for someone recently diagnosed.

"I still remember going back to practice in my small hometown in the '80s; they still had polio dinners. Polio was gone, but there were still many polio survivors, and the community still raised money for those kinds of charities. Those events drew communities together, they drew people to think about these demons that are out there, and anything that does that is good."



 
17-May-12
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