June 16 - Riggs' $192,270 NIH Grant Could Lead to Less Invasive Cancer Treatment
Dr. James Riggs, professor of biology at Rider University, has received a three-year, $192,270 grant from the National Institutes of Health to support undergraduate student-generated research that over the last ten years has evolved to the point where new findings could lead to less invasive ways to treat cancer.
His project will focus on immune regulation particularly in the peritoneal cavity or abdomen, and his current student assistants will work to decipher the mechanism that leads to immune suppression in the human body.
"There is increased production of an enzyme that depletes a crucial amino acid, trytophan. This, in turn, leads to suppression of immunity," said Riggs. "Other scientists have found that this same enzyme and amino acid depletion occur in cancer.
"This implies tumor cells create an immune suppressive environment around themselves so that the immune system fails to address the cancer," Dr. Riggs added. "This suggests we need to retool our thinking about immunity and cancer. Rather than using chemotherapy and radiation therapy, which have serious issues with respect to inducing mutations and the destruction of non-cancerous cells, we need to be thinking about how to flip the immune system's off switch back to on."
Dr. Andrew L. Mellor, a national leader in immunology, published in such prominent journals as Science and director of the MCG Immunotherapy Center at the Medical College of Georgia, finds the research being conducted at Rider significant to cancer research and meaningful to the undergraduate researchers. Dr. Mellor's lab has shown that active immune suppression plays a role in preventing the mother's immune system from attacking the fetus, which is actually foreign tissue.
"I met Dr. Riggs and one of his students, Kenny Yeh (a senior biology major and Mercer County Community College transfer) while attending the Experimental Biology 2005 Scientific Meeting in San Diego in April," Dr. Mellor said. "I was intrigued by their work, described on a poster at this meeting, because it was closely related to projects we have been actively pursuing for the past eight years at the Medical College of Georgia after our initial discovery of the immunosuppressive functions of the enzyme indoleamine 2,3 dioxygenase, or IDO for short.
"I was impressed by the quality of Kenny Yeh's research work given the early stage of his scientific career. It is gratifying to see students being encouraged to perform research of such high caliber and biological significance at such an early career stage, particularly when one's own ideas were the original source of the scientific inspiration for the work," Dr. Mellor added.
"But more importantly," he said, "I think the award of the NIH grant to Dr. Riggs testifies to his qualities as a student mentor and a source for their day-to-day motivation to go out and discover new knowledge through applying scientific methods. These days it is rare indeed to find undergraduate students' research work at international science meetings."
Dr. Riggs and his students have been intrigued that the intestinal track is loaded with bacteria, yet the immune system doesn't try to destroy it. This is a similar process to the mother's immune system not attacking the fetus that Dr. Mellor's lab found. "How the immune system behaves has always been an intriguing question for us," Dr. Riggs said. "We stumbled across an interesting observation that actually became the starting point for our current project."
Dr. Riggs had been studying cells in the peritoneal cavity for years, and was particularly interested in a subset of B-lymphocytes, antibody producing cells, found there.
“Studying these cells, we made the observation that peritoneal cells are suppressive and that they inhibited immune responses,” Dr. Riggs said.
He noted the initial experiments almost ten years ago were done by Carlo Rago, as an undergraduate student who currently is completing his Ph.D. in molecular medicine in Bert Vogelstein's laboratory at Johns Hopkins University. Rago, a 1997 biology graduate, was trying to determine if the abdominal B-cells could present a viral antigen to turn on T-lymphocytes.
"Carlo was comparing cells from the spleen versus cells from the peritoneal cavity," Dr. Riggs recalled. "The cells from the organized lymphoid tissue could present the viral antigen to the immune system, but the abdominal cells could not. There had to be a rational explanation for why that should occur.
"I did not believe the data when I first saw it," Dr. Riggs recalled. "We were focused on developing an AIDS model in mice. I asked him to repeat the experiments, and he observed the same results."
Dr. Riggs and his students decided to develop the model in another way and not concern themselves with these particular cells. Three years later, while following another line of investigation, they came across these experiments again.This time students did a cell mixing experiment where the one set of cells that could turn on the immune system was mixed with the other set that could not. “By mixing the cells, the response was suppressed,” Riggs continued. “We had found active suppression.”
That was in 2000, and subsequent student teams began further investigation. Students conducted experiments to determine if suppression was due to B-Cells or T-Cells and found it was neither. They eventually found that it was another type of cell called a macrophage.
All the while with his students challenging him with questions and ideas as he guided them, Dr. Riggs saw how the research was evolving and conceptualized the grant proposal.
Since joining the Rider faculty 14 years ago, Dr. Riggs has had almost $750,000 in grant funding for his immunology research and with the new grant now has had a total of 17 years of funding to support his work.
The eight-member Rider biology faculty has enjoyed solid success in attracting grant funding to support their research or provide equipment for state-of-the-art technology infrastructure. Over the years, they have received more than $3.5 million in grant support with $1,130,000 committed to current research, all with undergraduate researchers.
Dr. Riggs finds the new NIH grant his most gratifying because it reflects a body of research done entirely at Rider and represents an evolution of ideas generated with undergraduate students.
"It is exciting because we are investigating a new way to think about the immune system and cancer treatment," he said. "It is also exciting because undergraduates are conducting all of the work and learning to think critically as they become scientists."
