# Resolving complex alternative splicing of psychiatric disease genes using single-cell approaches

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $841,691

## Abstract

PROJECT SUMMARY
Schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorder (ASD) are common and debilitating
neurodevelopmental disorders that together affect more than 5 million Americans. Despite more than fifty years
of research, no cures exist and the standard of treatment remains unsatisfactory. Dysregulation of alternative
splicing in the human brain has been implicated in SZ. Among genes with critical brain functions, many have a
large number of exons, resulting in complex splicing patterns that can vary between neuronal subtypes;
however, the isoform repertoires of most of these complex genes have not been resolved in a cell-type specific
manner. Recent advances in long read sequencing have provided an unprecedented opportunity to resolve
complex alternative splicing. Thus, to better understand the clinical impact of changes of alternative splicing in
psychiatric diseases, it is critical to evaluate how isoform repertoire impact neuronal maturation and synaptic
function in a cell-type specific manner. Here, we propose to catalog and functionally characterize the
complexity of human isoform repertoires of SZ-associated genes using a single-cell long-read sequencing
based approach, and to study how genetic variations influence alternative splicing and impact neuronal
maturation and synaptic function in a subtype specific manner. This project will provide comprehensive
catalogs of cell-specific full isoform repertoires of SZ genes that will broadly facilitate SZ research. It will also
deepen the understanding of how genetic variations and alternative splicing contribute to SZ, help better
predict the clinical outcome and identify novel therapeutic interventions. The single cell approach used in this
project is generally applicable to study other mental disorders such as BD and ASD.

## Key facts

- **NIH application ID:** 10838481
- **Project number:** 5R01MH125579-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Kristen Jennifer Brennand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $841,691
- **Award type:** 5
- **Project period:** 2021-08-05 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838481

## Citation

> US National Institutes of Health, RePORTER application 10838481, Resolving complex alternative splicing of psychiatric disease genes using single-cell approaches (5R01MH125579-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10838481. Licensed CC0.

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