# Environmental Epigenomics and Precision Environmental Health

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $918,277

## Abstract

Abstract
Toxicant exposures early in life adversely affect health outcomes in both animal models and humans, in part
due to epigenetic mechanisms. Accumulating studies also indicate that exposures' impact on the epigenome
can be tissue and even cell specific. Yet, toxicoepigenetic animal studies are often conducted with single
tissues in bulk and/or limited epigenomic targets (e.g. DNA methylation). Additionally, epigenetic epidemiology
analysis of toxicants is almost always restricted to biologically available, “surrogate” (e.g. blood) samples.
Using a combination of toxicological and epidemiological approaches, the first of two overarching goals of this
Revolutionizing Innovative, Visionary Environmental Health Research (RIVER) application is to advance the
understanding of the effects of representative perinatal exposures (e.g. metals including lead and endocrine
active compounds including phthalates) on the epigenome and longitudinal health risks. To accomplish this, we
will use human physiologically relevant mouse models and longitudinal human birth cohort samples alongside
targeted and unbiased approaches to evaluate DNA methylation, non-coding RNA, chromatin structure, and
gene expression in both sexes in multiple tissues, incorporating single cell approaches when relevant.
Ultimately, we seek to identify tissue-specific epigenomic signatures of exposures contributing to disease
susceptibility as well as regions of the epigenome that may be interrogated with the use of surrogate tissues.
While precision modification of the epigenome holds great promise to modify environmentally induced changes
and reduce disease risk, it is currently out of reach using common available global (e.g. azacytidine) and
targeted (e.g. TALENs, CRISPR) systems. Thus, our second overarching goal is to advance the development
of a suite of tools, based on the PIWI-interacting RNA (piRNA) system to transform precision environmental
health, while avoiding drawbacks of current technology. In mice, we have shown that piRNA and associated
processing machinery are present and active in somatic tissues, especially the brain, in contrast to prior belief
that the piRNA suppression system was restricted to the germ-line. Evidence from our viable yellow agouti
(Avy) mouse experiments supports piRNA-based DNA methylation induction in vivo. Thus, we propose to use
this class of RNA to develop precision environmental health tools to target specific genes and loci for stable,
mitotically heritable, silencing in somatic cells. First, we will evaluate piRNA/PIWIL machinery across somatic
human tissues to prioritize cell types with high endogenous piRNA machinery for epigenetic editing. Then, we
will develop synthetic piRNAs to target DNA methylation in vitro in exposed rodent and human cell lines. The
research will expand the repertoire of human epigenome editing tools resulting in therapeutics to treat a broad
array of environmental and epigenetic diseases including imprinted gene...

## Key facts

- **NIH application ID:** 10162591
- **Project number:** 5R35ES031686-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Dana Dolinoy
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $918,277
- **Award type:** 5
- **Project period:** 2020-05-11 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162591

## Citation

> US National Institutes of Health, RePORTER application 10162591, Environmental Epigenomics and Precision Environmental Health (5R35ES031686-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10162591. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*