A $10.3 million grant from the California Institute for Regenerative Medicine (CIRM), the state’s stem cell agency, will fund a multi-UC effort to better understand neuropsychiatric disorders.
One in five people in the U.S. experience a neuropsychiatric disorder, with many cases starting in adolescence. Current treatments focus on managing symptoms, but there’s an urgent need to develop more effective therapies to address the root biological causes of these disorders.
The project team, which includes UC Santa Cruz Genomics Institute Research Scientist Mohammed Mostajo-Radji along with researchers from UC Los Angeles and UC San Francisco, aims to fill this gap by investigating the role of metabolism in human brain development and neuropsychiatric disorders at key developmental stages.
This work immediately paves the way for innovative, targeted therapies that include dietary interventions and new drugs to transform care.
“There’s quite a bit of evidence linking some types of Autism spectrum disorders to issues in metabolism, which would mean that potential treatments may be hiding in plain sight,” Mostajo-Radji said. “This project brings together experts throughout the state to test interventions that could be easily translated into treatments.
Mostajo-Radji and collaborators will work with 3D brain organoids — miniature models of brain tissue grown in the lab — grown from cells from patients with schizophrenia and autism spectrum disorder. They will use these models to compare how metabolism drives development in a healthy versus disrupted environment.
The team, comprised of experts in metabolism, computational biology, and neurodevelopmental disorders, has also created an innovative technological framework that models neurovascular interactions and has the flexibility to mix and match neural and vascular cells from control or affected individuals — a system that will help pinpoint which cell types are affected by these conditions and how.
Mostajo-Radji, an expert in organoid models and a member of the Braingeneers group, will focus on electrophysiological measurements of the brain tissue models.
“At the Braingeneers group, we have made major advances in assessing and modeling neuronal circuits,” Mostajo-Radji said. “We have developed protocols to make very good organoid models, and have created tools to both standardize the data analysis and assess the effects of perturbations in these organoids. Now, we are bringing these advances to test an incredibly cool question that can lead to making a big impact in society. We are extremely thankful to the people of California and CIRM for making this project possible.”
To maximize the impact of their findings, the research team plans to openly share data in accessible formats and collaborate with other groups in the field.
This project’s funding comes after CIRM awarded a $12.3 million grant to a team of researchers at UC Santa Cruz, UCSF, and UC Berkeley to study the genetic roots of autism, which was complemented with an additional $1.8 million grant from the UC Office of the President.
“CIRM remains deeply committed to accelerating stem cell and gene therapies for patients in need,” said Rosa Canet-Avilés, Chief Science Officer at CIRM. “We are excited to support these groundbreaking projects, advancing research from discovery to clinical impact.”
