CIRM awards more than $28 million to Scripps Research faculty members

The two distinct awards will support collaborative research projects into pollution’s impact on autism as well as risk genes in psychiatric disorders.

October 14, 2024

LA JOLLA, CA—Two Scripps Research faculty members and their multi-investigator teams were recipients of the latest round of funding from the California Institute for Regenerative Medicine (CIRM), with awards totaling more than $28 million to support large, collaborative research into environmental causes of autism as well as genetic psychiatric disorders.

Stuart Lipton, MD, PhD, professor, Step Family Foundation Endowed Chair in the Department of Molecular Medicine, and founding co-director of the Neurodegeneration New Medicines Center at Scripps Research, and his team were awarded about $17.5 million to study the impacts of air pollution on the human brain and how it contributes to the development of autism via a chemical reaction he discovered called protein S-nitrosylation (or SNO).

Xin Jin, PhD, associate professor in the Department of Neuroscience and the Dorris Neuroscience Center, and her team—alongside colleagues at the Salk Institute and University of California San Diego—were awarded more than $11 million to uncover how different cell types and epigenetic networks are impacted by risk genes implicated in human neuropsychiatric disorders.

Both awards are part of CIRM’s ReMIND-L initiative, a multi-collaborative initiative designed to accelerate the discovery of mechanisms underlying neuropsychiatric disorders leading to the identification and validation of novel targets and biomarkers. The goal is to provide new avenues and rigorous foundations for future translational and clinical investigations. To achieve this, the ReMIND Program will catalyze innovative, cross-disciplinary collaborations and support broad knowledge-sharing among research scientists and other stakeholders.

CIRM has provided billions in funding to support stem cell, genetic research, and development programs in its portfolio. Through the agency’s research, infrastructure, and education programs, CIRM aims to transform the field of regenerative medicine.

Pollution’s influence on autism and intellectual disability

Lipton’s four-year grant will support his research into air pollution effects—including vehicle exhaust, tobacco smoke, and wildfires—and its impact on a chemical reaction referred to as “SNO.” This reaction results from exposure to air pollution, in which nitrogen and oxygen atoms combine with a sulfur atom on a wide variety of proteins and disrupt their function, resulting in brain damage. This work, in collaboration with Scripps Research professor John Yates, III, will utilize mass spectrometry to discover proteins involved in SNO reactions that may play a role in the development of autism and intellectual disability. By further exploring these proteins, Lipton hopes to reveal key disease targets for new medicines.

“By awarding arguably the largest grants ever funded to study these effects of air pollution, CIRM is making a huge investment into chemical biology at Scripps Research and also human health—in this case, to study climate change’s impact on these major diseases that affect both the young and old,” says Lipton.

Lipton has a track record of developing FDA-approved drugs for neurological diseases, such as memantine (marketed as Namenda®, NamendaXR®, and Namzaric®) and other congeners (GoCovri®). His lab is using this chemistry to create novel treatments for autism-spectrum disorder as well as a range of intellectual and developmental disabilities. His lab focuses on researching basic molecular signaling pathways to protect synapses and prevent neuronal injury in aging and neurodegenerative diseases. Along these lines, the National Institute on Aging (NIA) of the NIH recently made a companion award for Lipton to study the chemical biology of air pollution in Alzheimer’s disease and related dementias.

Studying risk genes of psychiatric disorders

Jin’s four-year grant involves the development and application of state-of-the-art functional genomic analysis to seek mechanisms and to design therapeutic agents that address the root cause of psychiatric disorders. By approaching both the basic mechanisms of these disorders and the development of therapeutics, she and her team hope to transform how we understand and ultimately treat these conditions.

“This ReMIND-L award will enable exciting collaboration networks in Southern California and help us make meaningful progress toward our goal of developing novel therapeutics,” Jin says. “We’re grateful to CIRM for recognizing the importance of alleviating serious mental health disorders and the devastating impacts these conditions can have on families across the country.”

Jin’s work at Scripps Research focuses on developing cutting-edge technologies to uncover different genes, cells and brain regions that are involved in neurological conditions. Using these tools and a gene editing method she pioneered called in vivo Perturb-seq, she is on the forefront of mapping the brain’s genome. This work was recently highlighted in a study in Cell, where Jin and her team demonstrated the ability to profile tens of thousands of cells simultaneously via Perturb-seq and CRISPR screening methods—enabling the study of hundreds of genes in hundreds of diverse cell types in just days.

About the California Institute for Regenerative Medicine (CIRM)

At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of today’s most promising stem cell technologies.

CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of regenerative medicine closer to reality. For more information go to www.cirm.ca.gov.

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