# Bidirectional control of Chd2 haploinsufficiency

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $521,059

## Abstract

ABSTRACT
Major advances have been made in mapping the genetic basis of epilepsy and other neurodevelopmental
disorders (NDDs). In many cases, a candidate gene mutation has been identified, but there is no robust
understanding of the neuronal causes for the particular disorder. Mutations in genes encoding chromatin
regulators are commonly identified in human NDDs, with intellectual disability, autism and/or epilepsy often co-
occurring in the same individual. Our recent work showed that mice with germline heterozygous mutations in
Chd2 exhibit pathological changes across genomic, anatomical, electrophysiological and behavioral domains.
Here, we propose studies to bidirectionally control Chd2 dosage in the developing or adult brain. Our approach
involves a combination of sophisticated cellular, molecular, pharmacologic and electrophysiological
approaches in conditional Chd2+/- mice and human-derived neurons. If successful, our results will provide
important new information about the effects of chromatin regulators in driving NDD-associated pathologies in
vivo and would provide critical proof-of-concept for the therapeutic potential of pharmacologically increasing
Chd2 expression that could be rapidly translated into a new targeted therapy for Chd2 haploinsufficiency.

## Key facts

- **NIH application ID:** 10758254
- **Project number:** 5R01NS126399-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Robert F Hunt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $521,059
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758254

## Citation

> US National Institutes of Health, RePORTER application 10758254, Bidirectional control of Chd2 haploinsufficiency (5R01NS126399-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10758254. Licensed CC0.

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