# DREAM Mediated Transcription Acts as a Biomarker for Pollutant Induced Calcium Signaling Disruption

> **NIH NIH SC3** · CALIFORNIA STATE UNIVERSITY LONG BEACH · 2023 · $108,413

## Abstract

Summary/Abstract
Chemicals such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and triclosan
alter cellular Ca2+ signaling acting through L-type voltage-sensitive Ca2+ channels (CaV1) and/or ryanodine
receptors (RyR), which regulate the entry of Ca2+ from external sources or the release of Ca2+ from internal
stores, respectively. These channels alone are central to the function of a vast number of cellular signaling
processes and chemical disruption of these targets is correlated with altered dendritic growth, altered
neuromuscular health, and altered learning and memory in exposed model organisms. The list of toxicants, and
their receptor targets, that lead to such Ca2+ signaling disruption (CSD; used for disruption and disrupting) is
currently unknown. However, based on structural similarities to known CSD compounds, we hypothesize that a
large number of chemicals currently in use or in the environment are capable of CSD representing a need for
high-throughput tools able to screen individual chemicals and complex environmental mixtures. Recent work has
identified the downstream regulatory element antagonistic modulator (DREAM) which is the only Ca2+ sensor
identified to date that binds specifically to DNA and regulates transcription in a Ca2+-dependent manner. Thus
the DREAM protein acts as a direct connection between changes in intracellular Ca2+- and gene transcription
Our preliminary work demonstrates that select CSD compounds can alter DREAM mediated transcription in
model cell lines representing a unique opportunity to establish a CSD screening assay.
Here, we take a multi-tiered approach to extend our understanding of DREAM, in-light-of pollutant responses,
by screening known and predicted CSD chemicals for their ability to drive DREAM transcription in luciferase
transfected cell lines and evaluating the extent of DREAM mediated transcription or altered phenotypes in CSD
exposed wildtype and DREAM knockout zebrafish. The proposed work will establish gene transcription as a toxic
outcome due to CSD and lead to the development and validation of important cellular and animal tools able to
cost and time effectively evaluate large numbers of compounds for CSD activity. This work has vast implications
on the health of exposed organisms as DREAM is known to contribute to such processes as learning and
memory, pain reception and endocrine signaling in the hypothalamus, pituitary and the thyroid gland and has
been associated with Huntington’s disease, a
myotrophic lateral sclerosis
and type II diabetes. Understanding
the role of CSD in these physiological and pathophysiological states would aid in pollutant associated risk
assessment.

## Key facts

- **NIH application ID:** 10565950
- **Project number:** 5SC3GM132033-04
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY LONG BEACH
- **Principal Investigator:** Erika B Holland
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $108,413
- **Award type:** 5
- **Project period:** 2020-04-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10565950

## Citation

> US National Institutes of Health, RePORTER application 10565950, DREAM Mediated Transcription Acts as a Biomarker for Pollutant Induced Calcium Signaling Disruption (5SC3GM132033-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10565950. Licensed CC0.

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