Recent studies conducted at Rider University found that CD28, a protein under study to treat autoimmune diseases and cancers, could actually suppress rather than increase the T-cells needed to promote proper immune function. The paper, “CD28 ligation increases macrophage suppression of T cell proliferation,” was published in the July issue of Cellular & Molecular Immunology.
The research, which was supported by grants from the National Institutes of Health (NIH) AREA program and individual fellowships for Rider students, has implications for future cancer investigations. It also illustrates the impact that Rider’s scientific partnerships and research opportunities have on its students. Eight of the authors were involved in the research as undergraduate students and relied on the experience as they pursued graduate and medical programs. The paper also has co-authors from Bristol Myers-Squibb in Princeton and Harvard Medical School.
Dr. James Riggs, professor of Biology and one of the authors, said the research evolved approximately seven years ago from a partnership he established with John Somerville, a scientist in the Immunosciences Division of Bristol-Myers Squibb and a co-author.
“Classically, we think of cancer as being treated by radiation and chemotherapy. The treatments can be pretty nasty for the patient because it can cause damage to cancer cells and healthy cells,” Riggs said. “Squibb has become a leader in new ways to treat tumors and cancers that involves turning on the immune response to fight the cancerous cells.”
One less toxic treatment involves injecting patients with a biological drug or protein. Over the years, inside Riggs’ lab on the Lawrenceville campus, undergraduate student researchers tested the effects of the protein, CD28, in a tissue culture model mirroring a tumor microenvironment. The researchers wanted to test different strategies to turn on an immune system that has been turned off within the tumor.
“CD28 is a protein that activates the T-cells. It does this when T-cells are normal,” Riggs said. “However, our studies proved that when you activate T cells in a tumor microenvironment, the CD28 protein further suppresses the immune system. It’s counterintuitive.”
Arlene Sharpe, a professor of Pathology at Harvard Medical School in Cambridge, Mass., also co-authored the paper and provided an important strain of mice for the study. Riggs was introduced to Sharpe through Rider Biochemistry alumnus Daniel Barber ’97. Barber, who is now running his own lab a division at the NIH, had published work with Sharpe while he was pursuing his doctorate in Immunology at Emory University.
The authors also include Rider alumni Daniel Silberman ’08, Amanda Bucknum ’08, Thomas Bartlett ’10, Gabriella Composto ’10, Megan Kozlowski ’10, Amanda Walker ’11 and Jackelyn Cua Ovalle ’11. Riggs said the research experience definitely set the students apart when they were applying to graduate and medical schools.
Silberman, the primary author of the recent paper, was supported by fellowships from the New Jersey Commission for Cancer Research and the Rider University Marvin Talmadge Memorial Research Fund. Currently, he is a fourth year Ph.D. candidate in immunology at National Jewish in Denver, Colo., and is advised by John Kappler, a Howard Hughes Medical Institute Investigator.
“Dan was interviewed at every school he applied to,” Riggs said. “Having the opportunity to talk about his research really sold him as a Ph.D. candidate.”
Meanwhile, Kozlowski is a D.O. candidate at Philadelphia College of Osteopathic Medicine. Her undergraduate work has also appeared in a number of published papers.
“Dan and Megan are prime examples of students who came in as freshmen with AP credits from high school and an accelerated curriculum,” Riggs said. “They came right in the lab and hit the ground running. Those two really had an impact on the work that our lab does.”
Bucknum is an M.D. candidate at Temple University in Philadelphia. Riggs is still publishing what she’s worked on in his lab.
“She’s a really bright student,” he said. “Her med school interview sealed the deal. She had a great story to talk about from her research experience as an undergraduate.”
Bartlett is pursuing a doctorate in Molecular Biology at Princeton University. Riggs remembers giving a talk about opportunities at Rider for community college students a few years ago. Bartlett was one of the students who transferred to Rider and worked in the Biology department where he refined his interest in molecular biology.
Composto is a research technician in the Pharmacology/Toxicology Department at Rutgers University. “Her prospective boss was impressed by how much research experience she had,” said Riggs, noting that some of her other work has been published before.
Walker was supported by a Rider Undergraduate Research Scholar Award and was recipient of a Van Arman Scholarship Award from the Inflammation Research Association. As part of the award, she was able to present at a conference of the Inflammation Research Association. She was the only undergraduate student at the conference. In the fall, she will begin her Ph.D. studies in Physical Therapy at Rutgers University.
Finally, Ovalle, a December 2011 graduate and McNair Scholar, is applying to medical school.
“This is what Rider is all about — what the Sciences are all about,” said Riggs about the students’ success. “If the students work hard, the opportunities are phenomenal, and these are students who took advantage of everything placed before them.”