# CRISPR screens of population relevant genes governing toxicant resilience

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $653,678

## Abstract

People vary considerably in their response to and in the effects of exposure to chemical toxicants and
biological toxins. As a result, the risk of adverse outcomes associated with exposure for different individuals
and populations can be widely divergent. Gene by environment (G x E) interactions likely underlie a significant
component of these risk differences. However, we remain largely ignorant of both the key genetic factors and
the mechanistic association with specific toxins/toxicants. As a result, our capability to mitigate risk by the
identification of susceptible individuals and populations to enable effective preventive efforts remain sorely
limited. Current approaches to identify G x E interactions rely on genetic association studies which generally
lack sufficient power to identify significant associations, due to the large number of genetic variants and small
populations of exposed individuals. We propose, in a fundamentally different approach, to first systematically
identify the common human variants which impact the functional response to a specific toxicant/toxin to
delineate key candidate G X E interactions for targeted consideration in relevant individuals and populations.
We will focus on functional interrogation of 1490 genes, the ToxVar set, which contain an aggregate frequency
of loss of function mutations of >0.1% in all human populations assessed to date and previously identified as
interacting with one or more toxicant/toxins. We contend that these commonly functionally compromised
genes are most likely to impact human response to a toxin/toxicant in a significant proportion of people. We
will simultaneously query the impact of functional disruption in each of these 1490 genes on the cellular
response to a toxicant using coupled CRISPR screening and single cell toxicologically relevant gene
expression targets (scTRGETs). We will evaluate the ToxVar-scTRGET approach to identify functionally
relevant and commonly variant genes involved in cellular response to selected toxicants of high human
relevance in increasingly physiologically relevant cell models.

## Key facts

- **NIH application ID:** 10573193
- **Project number:** 5R01ES033625-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** CHRISTOPHER D VULPE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $653,678
- **Award type:** 5
- **Project period:** 2022-02-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10573193

## Citation

> US National Institutes of Health, RePORTER application 10573193, CRISPR screens of population relevant genes governing toxicant resilience (5R01ES033625-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10573193. Licensed CC0.

---

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