# Administrative supplement for R01 ES028738

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, MERCED · 2020 · $64,475

## Abstract

Project summary (from the parent R01)
Neurodevelopmental disorders (NDDs) are becoming more prevalent among our children at an alarming rate.
Studies suggest that NDDs may be caused by inadvertent early-life exposure to environmental toxins and
pollutants, especially the ones that are abundant indoors. We will study neurodevelopmental roles of one such
group of persistent environmental pollutants, polybrominated diphenyl ethers (PBDEs). This family of
organohalogenated flame-retardants is used in several household products worldwide, with PBDE-47 being the
most abundant in our environment. Our central hypothesis is that chronic exposure to PBDE-47 and its
metabolites disrupts neurodevelopment by dysregulating epigenetic mechanisms that orchestrate
neurodevelopmental gene transcription. This proposal will test our central hypothesis via three specific aims. 1.
We will determine if chronic exposure to environmentally relevant concentrations of PBDE-47 alters cortical
neurodevelopment. Experiments to test this possibility will be conducted in rat and human neuronal progenitor
cells (rNPCs and hNPCs) differentiating in vitro and in rats in vivo. Here, differentiating NPCs will be chronically
exposed to environmentally relevant doses of PBDE-47 and its metabolites and neuronal maturation will be
subsequently assessed electro-physiologically and functionally. 2. We will determine mechanisms of global
gene deregulation due to chronic exposure to PBDE47. Genome-wide assays (RNA-seq, ChIP-seq, and
CAP-seq) will be employed to test our hypothesis. 3. We will determine if chronic exposure to PBDE-47
and its metabolites alters the BAF (mammalian SWI/SNF) chromatin remodeling complex and thereby
chromatin permissiveness and gene transcription during neurodevelopment. Here, we will test the effects of
chronic PBDE exposure on functions of the BAF complex, a chromatin-remodeling complex that is highly
relevant for neurodevelopment-related gene transcription. We will mainly focus on a key BAF complex
component, BAF170 (SMARCC2). BAF170 is a candidate autism gene and is a ‘hit’ in our preliminary
screening of PBDE-impacted genes. We will use RNAi and CRISPR-based technology to understand the role
of BAF170 in neurodevelopmental gene expression, especially when challenged with PBDE-47 exposure.
Taken together, this study will provide deeper insights into epigenetic mechanisms driving neurodevelopment
and how persistent environmental pollutants may modulate NDD risks by interfering with these mechanisms.
Note: Supplemental support is requested for the bold section.

## Key facts

- **NIH application ID:** 10150422
- **Project number:** 3R01ES028738-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Ramendra N Saha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,475
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150422

## Citation

> US National Institutes of Health, RePORTER application 10150422, Administrative supplement for R01 ES028738 (3R01ES028738-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150422. Licensed CC0.

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