A team of researchers from the UCSF Broad Stem Cell Center, UCLA, and the UC Santa Cruz Genomics Institute is developing new stem cell-based treatments for neuropsychiatric disorders.
Investigating Metabolic Drivers of Neuropsychiatric Disorders
The research aims to identify neurovascular mechanisms underlying neuropsychiatric disorders. Led by co-PIs Aparna Bhaduri, PhD (UCLA), Heather Christofk, PhD (UCLA), Elizabeth Crouch, MD, PhD (UCSF), Harley Kornblum, MD, PhD (UCLA), Mohammed Mostajo-Radji, PhD (UCSC), and William Zeiger, MD, PhD (UCLA), the project focuses on how metabolism influences brain development and contributes to conditions such as schizophrenia and autism spectrum disorder (ASD).
Neuropsychiatric disorders affect one in five people in the U.S., often emerging during adolescence. Current treatments primarily manage symptoms rather than addressing the root biological causes. This research aims to bridge that gap by uncovering metabolic factors that drive neurodevelopmental disruptions. “We hope that these studies will pave the way for identifying biomarkers for early detection and developing novel therapeutic strategies, including dietary interventions and targeted treatments for neuropsychiatric disorders,” explains Dr. Crouch.
Leveraging Advanced Stem Cell Models
The research team will use stem cell-derived 3D brain organoid models generated from patient samples to analyze metabolic differences between healthy and affected brains. Their innovative framework integrates neurovascular modeling, enabling them to examine how neural cells interact under both normal and pathological conditions. “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,” Dr. Mostajo-Radji said. “This project brings together experts throughout the state to test interventions that could be easily translated into treatments.”
The team, comprised of experts in metabolism, computational biology, and neurodevelopmental disorders, 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. Dr. Mostajo-Radji, an expert in organoid models and a member of the Braingeneers group, will focus on electrophysiological measurements of the brain tissue models.
Impact and Future Directions
This research will provide critical insights into how neurovascular metabolism influences human brain development and contributes to neurodevelopmental disorders. The research team plans to openly share data in accessible formats and collaborate with other groups in the field to maximize the impact of their findings.