# Project 3: Mapping Proteome-Wide Reactivity of Superfund Chemicals Using Chemoproteomic Platforms

> **NIH NIH P42** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $197,172

## Abstract

PROJECT 3: SUMMARY/ABSTRACT
Many hazardous chemicals at Superfund sites have been linked to adverse health effects, but their
toxicological mechanisms remain poorly understood.
This project will apply innovative analytical technologies
to dissect and simplify the complexities associated with analyzing the toxicological mechanisms associated
with exposure to chemical mixtures and the Exposome. We have developed a chemical proteomic technology
termed reactivity-based protein profiling (RBPP) that enables the mapping of direct interactions of
reactive SRP chemicals with protein targets in complex biological systems. This is a novel and very
innovative technology that enables a comprehensive assessment of how chemicals interact with specific
molecular targets directly in complex mammalian physiology, which in-turn informs the types of downstream
biochemical and pathological effects that may result from chemical exposure. This technology and the
information revealed from using it will vastly expand our knowledge of: 1) novel toxicological mechanisms of
individual SRP chemicals; 2) common pathways that may be targeted by multiple SRP chemicals; and 3)
toxicological mechanisms that may arise from exposure to chemical mixtures and other factors in the
Exposome. We hypothesize that dissecting out the individual targets of chemicals and mapping
common pathways that are targeted across multiple chemicals will enable us to identify particularly
important toxicological mechanisms associated exposure to complex chemical mixtures. We have been
using RBPP to profile direct protein targets of many widely used environmental chemicals of concern. We have
found that several protein targets involved in fatty acid degradation, metabolism, and steroidogenesis are
directly and commonly inhibited by a strikingly large number of reactive environmental chemicals. These
commonly targeted pathways are likely to result in adverse health effects since inhibiting the burning of fat will
lead to accumulation of fat in tissues and inhibiting steroid hormone degradation will lead to accumulation in
both hormones like testosterone and cortisol which may have behavioral and tumor promoting effects. We
hypothesize that cumulative exposure to these reactive SRP chemicals and the inhibition of protein targets
involved in fat and steroid metabolism will directly impact lipid and steroid levels in vivo in mice and humans.
We propose to apply innovative analytical platforms to map proteome-wide targets of reactive SRP
chemicals to reveal novel toxicological mechanisms with a particular focus on understanding how
exposure to SRP chemical mixtures may synergize to impact fat and steroid metabolism. This project
will directly address Problems 1, 3, and 4 on addressing the problem of: 1) mixtures, 2) complexities of
chemicals operating through unique and overlapping mechanisms, and 3) identifying risks associated with
chemical exposure in vulnerable populations, through using our innovative R...

## Key facts

- **NIH application ID:** 10136016
- **Project number:** 5P42ES004705-33
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Daniel Nomura
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,172
- **Award type:** 5
- **Project period:** 1997-04-01 → 2022-08-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136016

## Citation

> US National Institutes of Health, RePORTER application 10136016, Project 3: Mapping Proteome-Wide Reactivity of Superfund Chemicals Using Chemoproteomic Platforms (5P42ES004705-33). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136016. Licensed CC0.

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