Bottom left to right: Alysson Moutri, PhD; Lilia Iakoucheva, PhD; Sébastien Jacquemont; Trey Ideker, PhD
A team of UC San Diego researchers with support of a $12.5 million grant from the California Institute for Regenerative Medicine (CIRM) plans to use gene therapy advances to understand schizophrenia and autism and central nervous system disorders.
Led by principal investigator Jonathan Sebat, PhD, the team includes several scientists from UC San Diego’s Verge Center. The grant is part a CIRM program known as Research using Multidisciplinary, Innovative approaches in Neuro Diseases (ReMIND).
CIRM connected with Dr. Sebat to learn more about the research. Some of his responses have been edited for clarity and brevity.
What is the question that this project is hoping to address?
Dr. Sebat: Our new UC San Diego Verge Center will use a data‑driven approach to uncover the mechanisms behind psychiatric traits. Researchers will use advanced stem cell and brain organoid technologies to study how specific genetic mutations shape brain development. By bringing together experts in genetics, neuroscience, and clinical psychiatry from UC San Diego and partner institutions, the center will coordinate four major projects: clinical research, high‑throughput screening, organoid studies, and data science. These efforts build on strong existing programs focused on the genetics of psychiatric disorders.
What do you want to achieve through this research?
Dr. Sebat: The Verge Center aims to understand how genes linked to schizophrenia and autism converge on shared molecular pathways, cellular functions, and neurocognitive traits.
Our approach integrates genetics, neuroscience, and data science. Stem cell experts will use scalable platforms to study neural functions for more than 100 genes and copy number variants (CNVs). Clinical neuroscience teams will examine how these genetic factors affect cognition, psychiatric traits, and brain activity. Data scientists will merge cellular, clinical, and genetic data to identify core pathways and neurodevelopmental processes that shape early brain development.
Clinical teams led by Carrie Bearden, PhD, at UCLA and Sébastien Jacquemont, MD, at the University of Montreal will use large clinical, neurocognitive, and neuroimaging datasets from patients with specific gene mutations. They will also collect patient samples, convert them into stem cells and neurons, and link clinical features to molecular behavior in lab‑grown neurons.
Gene Yeo, PhD, and Anne Bang, PhD, at Sanford Burnham Prebys will apply high‑throughput screening to study more than 100 genes in brain cells. They will test how loss‑of‑function or gain‑of‑function mutations affect neurons derived from stem cells.
Lilia Iakoucheva, PhD, and Alysson Muotri, PhD, will study how genetic risk factors for autism and schizophrenia influence brain development using brain organoids—three‑dimensional models that mimic human brain structure and activity.
Trey Ideker, PhD, and I will analyze data on genes, pathways, and neuron function. Using statistical and machine‑learning tools, we will identify shared pathways and neurodevelopmental traits across hundreds of genes tied to schizophrenia and autism.
By integrating clinical data, genetic analysis, and functional studies of neurons and organoids, the center aims to reveal the biological mechanisms that drive these conditions. These discoveries could lead to better diagnostics and new treatments for psychiatric disorders.
How might this research change the way this disease is considered or studied by other scientists?
Dr. Sebat: To build evidence‑based psychiatric medicine, we need a clear mechanistic understanding of psychosis, depression, and anxiety. Something we still lack. The Verge Center uses data‑driven, gene‑first approach. We’ll define the molecular and cellular mechanisms that shape cognitive traits. This will show how specific neural processes in the developing brain influence mental health. It will guide the creation of new pharmacologic therapies.
Why is research for neuropsychiatric disorders and diseases affecting the Central Nervous System (CNS) is so important?
Dr. Sebat: Mental health is critical to the well-being of people from all walks of life. Like other health conditions, susceptibility to psychiatric disorders has a biological basis. Research in genetics and neuroscience is needed to have a basic understanding of how brain function relates to psychiatric traits and how this knowledge can be applied in mental health care.
How might the ReMIND program impact the work of CIRM?
Dr. Sebat: One of CIRM’s mandates is to advance research on brain diseases. This includes mental health disorders. These conditions involve many genes and raise scientific questions across multiple levels. Those issues span basic and clinical neuroscience. Traditional funding models cannot integrate genetics, neuroscience, and clinical psychiatry in a rigorous way. Coordinated, cross‑disciplinary collaboration across institutions is essential.
What has been CIRM’s impact over the last 20 years?
Dr. Sebat: As a neuroscience researcher in San Diego, I’ve seen firsthand how stem cell technologies have transformed the field. I’m also keenly aware of the central role CIRM has played in driving that progress.
Learn more about the ReMIND program at cirm.ca.gov/remind.
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