UToledo Researcher Looks to Early Brain Development for Answers to Epilepsy

UToledo Researcher Looks to Early Brain Development for Answers to Epilepsy

A University of Toledo researcher is using lab-grown miniature brain models to better understand a rare genetic form of epilepsy that begins in infancy and has no cure.

Dr. Wei Niu, an assistant professor in the Department of Molecular, Cellular and Developmental Biology in UToledo's College of Natural Sciences and Mathematics, has studied the condition for nearly a decade. Known as Protocadherin-19 (PCDH19)-clustering epilepsy, it causes groups of seizures that can continue for days or weeks, often first triggered by fever. Niu's research focuses on how changes in the PCDH19 gene can affect early brain development and potentially contribute to the condition.

A recently announced $587,758 grant from the National Institute of Neurological Disorders and Stroke in the U.S. Department of Health and Human Services will support her research into the cellular and molecular mechanisms behind the condition and potential therapeutic strategies to mitigate it.

"There's a lot that has been done, but not enough to understand how this protein is contributing to the PCDH19 epilepsy," Niu said.

The condition can also be associated with developmental delays, autism and intellectual disabilities, although its severity varies among patients.

Niu is particularly interested in understanding how Protocadherin-19 influences the earliest stages of human brain development, a period that is difficult to study directly.

"It's impossible to track fetal brain development using human tissue, but we have this approach to grow a simplified miniature brain structure in a petri dish in a lab," she said.

Niu established her brain organoid laboratory at The University of Toledo three years ago with startup funding provided by the University. Her team has since collected preliminary data that formed the foundation for her new federal grant.

The three-year award will allow researchers to expand their use of miniature brain models, advanced imaging and next-generation sequencing. By comparing healthy and PCDH19-epilepsy brain organoid models, researchers will be able to examine differences at the level of individual cells and determine how those changes affect the developing brain.

The findings could help identify biological pathways involved in the condition and guide future efforts to develop treatments.

"Right now, there is no cure for PCDH19 epilepsy," Niu said. "The patients and families quite desperately need a cure because it's affecting them very early in the infant stage. That's the ultimate goal."

The funding will also support collaborative research with Dr. Jack Parent and his team in the Department of Neurology at the University of Michigan. In addition to advancing the research, Niu said the collaboration will create opportunities to train undergraduate students in interdisciplinary biomedical research.

Undergraduate students working with Niu will gain experience with human stem cell culture, brain organoid development, advanced microscopy and bioinformatics while learning how multiple research approaches can be used to investigate human brain development. Niu also hopes students will have opportunities to conduct summer research under Dr. Parent and learn more from his team of researchers.

"This is one of the impacts of this funding as well, to train undergraduate students in biomedical basic research," Niu said.

The emphasis on undergraduate participation supports The University of Toledo's focus on expanding experiential learning opportunities, giving students practical research experience that can help prepare them for graduate and medical programs.