Bottom row, left to right | William Zeiger, MD, PhD (UCLA), Heather Christofk, PhD (UCLA), Harley Kornblum, MD, PhD (UCLA)
A team of researchers from the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF and UCLA, along with the UC Santa Cruz Genomics Institute, has been awarded a $10.3 million foundational research grant from the California Institute for Regenerative Medicine (CIRM). The funding will support the development of new stem cell-based treatments for neuropsychiatric disorders.
Investigating Metabolic Drivers of Neuropsychiatric Disorders
The grant, part of CIRM’s ReMIND (Research using Multidisciplinary, Innovative approaches in Neuro Diseases) initiative, 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. CIRM’s ReMIND initiative, established through Proposition 14, directs at least $1.5 billion of its $5.5 billion in bond funding toward the research and development of treatments for diseases affecting the brain and central nervous system. “CIRM remains deeply committed to accelerating stem cell and gene therapies for patients in need,” said Rosa Canet-Avilés, PhD, Chief Science Officer at CIRM. “We are excited to support these groundbreaking projects, advancing research from discovery to clinical impact.”
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.
To learn more about the multidisciplinary project award, explore the following articles:
- UCLA scientists awarded $21.8 million in CIRM grants to advance novel stem-cell based therapies
- New grant funds effort to uncover therapeutic targets for neuropsychiatric disorders
- CIRM awards nearly $100 million to boost discovery, translational, and clinical disease research
- CIRM awards $67.5 million to address neuropsychiatric diseases through its ReMIND program
- California’s stem cell agency approves new plan to invest $110M into basic research in neuropsychiatric diseases