Michelle Theus, an associate professor of molecular and cellular neurobiology in the Department of Biomedical Sciences and Pathobiology within the Virginia-Maryland College of Veterinary Medicine, recently secured two grants totaling nearly $4.5 million from the National Institute of Health (NIH) for research related to traumatic brain injuries.
The funding came through the National Institute of Neurological Disorders and Stroke (NINDS), an institute within NIH that provides support for health-related brain research and development. Theus is the principal investigator on these two grants and two other previously secured NIH grants, along with being one of multiple principal investigators on a grant from the CURE Epilepsy foundation studying the effects of traumatic injury and stroke on brain function.
Each grant supports a specified project to be performed by a named investigator(s) in the investigator’s specific area of interest. Although funding at this level is an accomplishment for any researcher, Theus is modest about her success.
“I don’t know how much credit to take for it,” Theus said. “With [COVID-19], we’ve all been restricted to our home offices. I think being solely focused on writing grants has enabled my success. So, maybe I should give [COVID-19] credit for that.
“But I’m delighted once again to have the recognition from NINDS. I’m grateful they agree that this is a fruitful endeavor.”
One grant, totaling $2.01 million, will be used to study new mechanisms that promote entry of certain white blood cells into the immune-privileged brain and how this creates a neurotoxic environment that disrupts the blood brain barrier: a barrier that prevents immune cell entry and helps keep the brain safe and prevents proper functioning of neurons.
Theus has assembled an outstanding team of partners that include Virginia Tech Professor Chang Lu, post-doctoral fellows Elizabeth Kowalski, Erwin Kristobal Gudenschwager Basso, Eman Soliman, and John Leonard, as well as graduate student Jatia Mills.
“When that barrier is lost, and neurotoxic immune cells enter and do what it is they’re programed to do, the brain is not a conducive environment for that response,” she said. “Our goal is to devise innovative ways to re-tool their program, to limit their overzealous nature in a manner that enables the brain to heal as a consequence of head trauma.”
The other grant, totaling $2.47 million, allows for the study of age-dependence on the immune response. Exciting new findings from her group show that immune cell transfer from juvenile animals into adult animals exposed to traumatic brain injury resulted in substantial protection. Her long-term goal is to learn how to recondition the adult or aged immune system as a therapeutic tool to limit brain damage by taking advantage of the youthful program.
As part of her overall translational approach to science, Theus will begin to glean information from her research with animals by partnering with Biraj Patel and Eric Marvin, two clinicians in the Virginia Tech Carilion School of Medicine, to apply the work to human patient samples. She currently holds one Institutional Review Board for the upcoming proposals.
“If we understand the most efficient way to reprogram peripheral immune cells to respond within the brain-injured environment, this may open new avenues for therapy that could include preventative measures for our combat troops, or professional athletes,” Theus said.
Theus’s interest in studying traumatic brain injuries stems from both personal and professional experiences. A close childhood friend fell while hiking at a quarry park and has been dealing with the aftermath his whole life. Professionally, her research training at institutes such as the Cleveland Clinic and The Miami Project to Cure Spinal Cord Paralysis at the University of Miami has ingrained in her the broader impacts of basic science research.
At the end of this study, she and her team hope to find a pathway that enables a young immune system to respond in a way that appropriately promotes brain repair and limits damage in both middle-aged adults and seniors.
“My team is ready and poised to do this work,” Theus said. “We have much work ahead, and we’re looking forward to having a lot of fun while doing it.”