# Epitranscriptomic mechanism of environmental stress response and tumorigenesis

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $1,230,000

## Abstract

Abstract
 All organisms including humans are constantly exposed to various environmental agents that cause damage
to the DNA as well as other biomolecules, and thus threaten genomic integrity and cellular homeostasis, leading
to the development of various diseases such as cancer. During the past few years, supported by NIEHS funding,
my lab has carried out several screening studies, leading to exciting discoveries on the role of RNA modifications
in DNA repair, cellular homeostasis, and tumorigenesis induced by UV irradiation and arsenic, two known
carcinogenic agents. These results focus particularly on the most abundant internal mRNA methylation, N6-
methyladenosine (m6A) mRNA methylation. However, the major challenge is that how environmental agents
interact with the epitranscriptome in disease pathogenesis remains poorly understood. Based on the discoveries
made in our published work and our unpublished findings, I propose to test this overarching hypothesis:
environmental insults dysregulate the epitranscriptomic machinery and thus impair genomic integrity and cellular
homeostasis, leading to tumorigenesis. The focus of my R35 application is to determine the epitranscriptomic
mechanism of environmental stress response and tumorigenesis in biochemical systems, cells, and mouse
xenograft/orthotopic/genetic tumor models. As the research program evolves, we will then establish the
relevance of these discoveries in human samples. Furthermore, we will also expand our investigation to explore
how RNA modifications are modulated by other environmental carcinogenic agents, in skin cells and in epithelial
cells of other tissue origins that are targeted by these carcinogens. We will employ the novel m6A methylome
sequencing technology developed by our collaborator’s lab, as well as other sequencing technologies to map
the environmental epitranscriptome. In addition, we will continue to create new genetic mouse models to
investigate the role of RNA modifications in environmental tumorigenesis. My broad research program will pursue
the following goals: (i) establish the mechanism by which m6A RNA methylation regulates tumorigenesis
following UVB radiation and arsenic exposure; (ii) discover new enzymes that regulate m6A mRNA methylation
in environmental stress response and tumorigenesis; (iii) explore the roles of other RNA modifications in
environmental stress response and tumorigenesis; and (iv) identify new molecules that modulate RNA
modifications as probes/therapeutics. The resultant discoveries can vastly expand our knowledge to further
establish the role of environmental epitranscriptomics in stress response and cancer, and open up new
opportunities to develop new epitranscriptomics-based probes/therapeutics to improve prevention and therapy
for cancer as well as other diseases.

## Key facts

- **NIH application ID:** 10880649
- **Project number:** 5R35ES031693-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Yu-Ying He
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,230,000
- **Award type:** 5
- **Project period:** 2023-08-01 → 2031-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880649

## Citation

> US National Institutes of Health, RePORTER application 10880649, Epitranscriptomic mechanism of environmental stress response and tumorigenesis (5R35ES031693-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880649. Licensed CC0.

---

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