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 plans to use leverage stem cell and gene therapy advances better understand schizophrenia and autism as well as as other 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 apply advanced stem cell and brain organoid technologies to study how specific genetic mutations shape brain development. By uniting 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’s main goal is 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 combine 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 and cellular behavior in lab‑grown neurons.
Gene Yeo, PhD, and Anne Bang, PhD, of Sanford Burnham Prebys will apply high‑throughput screening to study the function of 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 investigate 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 methods, we will identify shared pathways and neurodevelopmental traits across hundreds of genes linked to schizophrenia and autism.
By integrating clinical observations, 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 currently lack. The Verge Center will use a data‑driven, gene‑first approach to define the molecular and cellular mechanisms that shape cognitive traits. This knowledge will clarify how specific neural processes in the developing brain influence mental health and 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, including mental health disorders. These conditions involve many genes and raise scientific questions at multiple levels, drawing on both basic and clinical neuroscience. Traditional funding models that support one investigator at a time do not allow for the rigorous integration of genetics, neuroscience, and clinical psychiatry. Coordinated, cross‑disciplinary collaboration across institutions is essential.orations across disciplines and institutions.
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.