# BAF complex inhibitors in neuronal development and functions

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, MERCED · 2022 · $204,124

## Abstract

PROJECT SUMMARY
Neurodevelopmental disorders (NDDs) are becoming more prevalent among our children at an alarming rate.
Recent genome-wide studies suggest a strong correlation between NDDs and loss-of-function mutations in
genes encoding subunits of the BAF (alias, mSWI/SNF) chromatin remodeling complex. Despite such strong
correlative evidence, the precise role(s) of the BAF complex in neurodevelopmental gene transcription remains
largely unexplored, in part, due to lack of efficient chemical/pharmacological tools to disrupt BAF function. In
response to the NIH funding opportunity titled, ‘Discovery of Cell-based Chemical Probes for Novel Brain
Targets’, this project will further develop and test a promising group of BAF inhibitors in maturing rat cortical
neurons and use these inhibitors to probe the function of these chromatin remodeling complexes in neuronal
activity-induced gene transcription, a key molecular driver of neuronal maturation. Specific aims of this project
are: 1) Chemically modify ‘hit’ molecule BAFi to increase potency in neuronal cells, and 2) Determine the role
of BAF complex in neurodevelopmentally important activity-induced gene transcription. The project will be
conducted simultaneously in two laboratories with long standing expertise in –respectively– development of
small molecule inhibitors of chromatin remodelers (the Dykhuizen laboratory at Purdue university; aim 1) and
activity-induced neuronal gene transcription (the Saha laboratory at University of California, Merced; aim 2).
Taken together, this study will generate valuable chemical tools to study BAF complex functions and deeper
insights into epigenetic mechanisms driving normal neurodevelopment, which will fill in the knowledge gap
between BAF mutations and their outcomes, such as NDDs.

## Key facts

- **NIH application ID:** 10528055
- **Project number:** 1R21MH128678-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Emily Carla Dykhuizen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,124
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528055

## Citation

> US National Institutes of Health, RePORTER application 10528055, BAF complex inhibitors in neuronal development and functions (1R21MH128678-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10528055. Licensed CC0.

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