# Monitoring Endoplasmic Reticulum Stress Caused by Chronic Exposure to Chemicals

> **NIH NIH P42** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $385,806

## Abstract

ABSTRACT: PROJECT 5
 Hazardous waste sites contain complex mixtures of a wide variety of toxic chemicals that contaminate and
linger in the environment. The acute toxicities of numerous Superfund (SF) chemicals have been extensively
investigated; however, further studies are needed to determine their chronic effects on human health. Several SF
chemicals (e.g. naphthalene, PCBs, and CCl4), which are found in environmental samples from the Yurok Tribe
of the Klamath River basin, and in California air, have been shown to induce endoplasmic reticulum (ER) stress
in cultured cells. Furthermore, in animal models, long-term exposure to CCl4 leads to ER stress in tissues,
resulting in fibrosis and organ damage. Thus, the central hypothesis for this project is that chronic exposure to
xenobiotics leads to ER stress that then contributes to chronic inflammation, tissue fibrosis and eventual organ
failure.
 Based on the novel concept that the magnitude of ER stress is proportional to the amount of chronic
exposure to chemicals, and monitoring ER stress will help predict resulting biological effects, the long term goal
of this project is to develop a high-content and medium throughput bioassay to test the potential of SF chemicals
to induce ER stress (Aim IIIA), and a biomarker of ER stress-associated biological effects for bio-fluid analysis
(Aim IIIB). Toward these objectives, cell-based assays (Aim I) will be used to understand the mechanisms by
which exposure to environmental toxins leads to ER stress. In addition, in animal models (Aim II, with Project 4),
Project 5 will evaluate the effects of chronic exposure to hazardous chemicals on ER stress, and test if seric
oxylipids are surrogate biomarkers for ER stress (with Cores A and B). The methodology developed and data
obtained from the cell cultures and animal models will be directly translated in developing biomarker assays
(Aim IIIA and B; with Projects 2 and 3, and Cores A and B). Finally, research findings will be utilized to serve
the community at large by testing field samples collected from the Klamath River basin, the Central Valley and
the Sierra Nevada foothills in California, and at or around SF-sites across the U.S. (Aim IIIC with Project 1,
Cores B, C and D), as well as transferring to the scientists of the Yurok Tribe Environmental Program (with
Core E).
 Accordingly, the overall goals of this project are to: 1) test lipid mediators as potential diagnostic biomarkers
for the magnitude of ER stress response that often contributes to organ damage, 2) develop fast, inexpensive
and reliable new cell-based bioassays to detect, assess and quantitate the effects of hazardous substances on
ER stress, 3) provide new mechanistic insights into the effects of chronic exposure to SF chemicals on ER stress
and fibrotic diseases, 4) develop biomarkers assays for bio-fluids for the quantification of tissue-specific effects of
xenobiotics on ER stress, and 5) translate our findings by assessing risk on hu...

## Key facts

- **NIH application ID:** 10179387
- **Project number:** 5P42ES004699-33
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Fawaz George Haj
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,806
- **Award type:** 5
- **Project period:** 1997-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179387

## Citation

> US National Institutes of Health, RePORTER application 10179387, Monitoring Endoplasmic Reticulum Stress Caused by Chronic Exposure to Chemicals (5P42ES004699-33). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179387. Licensed CC0.

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