Medical Student Studies Aggressive Pediatric Brain Tumors
A four-year National Cancer Institute fellowship will fund his ongoing research
Christian K. Ramsoomair, a fifth-year M.D./Ph.D. student in the Medical Scientist Training Program at the University of Miami Miller School of Medicine, has received a National Cancer Institute F30 fellowship, one of the most prestigious awards available to physician-scientists in training.
Ramsoomair’s four-year fellowship will provide a total of approximately $220,000 in funding. This highly competitive grant supports promising M.D./Ph.D. students as they develop the research skills needed for leading future breakthroughs while also delivering superb care to their patients.
His award will fund his research on a devastating brain tumor that affects children — diffuse midline glioma, or DMG.
“I want a career in pediatric neurosurgery where my basic science and clinical research interests can be directly translated to children suffering at the bedside,” Ramsoomair said. “I was jarred by the desperate need for efficacious therapies against DMGs and other pediatric brain tumors and am committed to providing hope for both patients and their families. I’m tremendously honored to receive this award.”
He aims to create a new route for anti-cancer action in DMG patients through a process called viral mimicry—increasing the potency of the pediatric-cancer-fighting field.
Although rare, DMG is the most aggressive form of brain cancer in children: The five-year survival rate remains under 1%. Fewer than 10% of patients survive beyond two years.
The F30 National Research Service Awards Fellowships help support trainees from Medical Scientist Training Programs during the last years of their Ph.D. and a comparable amount of time in their clinical (M.D.) training. The Miller School of Medicine is one of 56 medical schools in the U.S. with a Medical Scientist Training Program.
Diffuse Midline Glioma
Most DMGs occur in the pons, a critical part of the brainstem. The brainstem controls such vital functions as breathing, heart rate, swallowing and motor coordination. Because of its location, it is nearly impossible to surgically remove the tumor without risking catastrophic outcomes, such as paralysis, loss of basic functions or death.
DMGs are stubbornly resistant to existing therapies, such as immunotherapies. These latter treatments, specifically immune checkpoint inhibitors, which harness the body’s immune system to fight cancer, are making inroads against non-solid tumors. But they have essentially failed in cases of DMG.
One reason is that DMG is considered an immunologically “cold” tumor: There aren’t enough immune cells near the tumor to sound the alarm and trigger an immune response. Because many immunotherapies work by helping the immune system recognize and attack cancer, these treatments have had limited success against DMG.
Ramsoomair’s research aims to overcome such constraints by using viral mimicry, a novel approach showing early promise against other cancers.
“Chris is a phenomenal student who’s really changed the course of our lab,” said Ashish H. Shah, M.D., assistant professor of neurological surgery and one of Ramsoomair’s mentors. “He’s highly dedicated to his work and has already brought lots of innovation to the table in his young career.”
Viral Mimicry
Rather than relying solely on the immune system’s natural ability to detect and eliminate cancer, viral mimicry strategies aim to “trick” the immune system into recognizing cancer cells as if they were virally infected — prompting a more robust immune response.
By reprogramming DMG tumors to act more like a virally infected cell, Ramsoomair will seek to activate the immune system, turning a “cold” tumor into a “hot” one that’s easier for the body to attack.
Ramsoomair’s research focuses on a protein called ADAR, which edits a type of RNA known as double-stranded RNA, or dsRNA. This form of RNA is usually associated with viruses but can be elevated in DMG also; it acts as a warning signal to the immune system. Under normal conditions, ADAR keeps the immune response in check by editing dsRNA so it doesn’t trigger unnecessary inflammation. In these tumors, however, ADAR becomes overactive. It edits the dsRNA so thoroughly that the immune system no longer sees it as a threat, allowing the cancer to remain hidden.
Early findings from Ramsoomair and his team suggest that when ADAR is turned off in patient-derived tumor cells, the effect is striking. The unedited dsRNA builds up and mimics a viral infection, which awakens the immune system. At the same time, the tumor cells start displaying more surface signals that make them easier for immune cells to detect and destroy. By removing ADAR’s suppressive influence, the cancer effectively loses its invisibility cloak.
By turning the tumor’s own biology against itself, Ramsoomair hopes to transform what was once an invisible enemy into a visible target for the immune system. In doing so, he may help shift the future of care for children with this heartbreaking diagnosis.
“Everyone in the Medical Scientist Training Program is extremely proud of Chris’s achievement,” said its co-director Alessia Fornoni, M.D., Ph.D., assistant dean for research training and development, and a professor of medicine and molecular and cellular pharmacology. “He is an outstanding choice for this prestigious award.”
Tags: brain cancer, brain tumors, cancer research, Medical Scientist Training Program, National Cancer Institute, Sylvester Comprehensive Cancer Center