# Developmental Exposures, Stem Cell Reprogramming, and Breast Cancer Disparties

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $457,207

## Abstract

ABSTRACT
The overall goal of this project is to define how interactions between breast stem cells and environmental
stressors drive the biological basis of racial disparities in triple negative breast cancers (TNBCs). TNBC
incidence in African American women is two to three-fold higher than in European Americans. The biological
mechanisms underlying this striking disparity are not well understood. Our preliminary data identifies
widespread racial disparities in exposure to a multitude of environmental toxicants including phthalates and
parabens. The breast cancer windows of susceptibility hypothesis states that environmental exposures in
utero, or during puberty and pregnancy, disproportionately increase breast cancer risk. Exposures during
windows of susceptibility could modify risk by the increasing the number of stem cells, altering stem cell
epigenetic reprogramming, or by otherwise changing stem cell biology. Using single cell RNA expression
profiling, we have identified a rare breast stem cell population with hybrid epithelial/mesenchymal
characteristics and an RNA expression pattern resembling TNBCs. What factors regulate these cells, including
the influence of race/ethnicity or environmental exposures, are unknown. The objective of this proposal to
dissect the role of stem cells and the environment in the biology of TNBC racial disparities. We will
experimentally challenge normal human breast stem cells isolated from epidemiologically well characterized
women ex vivo with prototypical toxicants and toxicants prioritized because of racial exposure disparities. Our
central hypothesis is that differences in normal stem cell biology, attributable to either genetic or environmental
factors (or a gene-environment interaction), underlie TNBC disparities. We will test this hypothesis with three
Specific Aims: (1) Test for differences in normal breast stem cell biology in African American and European
American women by single cell RNA sequencing, three-dimensional ex vivo culture, and epigenomic profiling.
(2) Define the disparities in exposure to environmental toxicants between African American and European
American women in a nationally representative dataset. (3) Test for differential effects of environmental
toxicants on African American and European American breast stem cells. This interdisciplinary study will use
state-of-the-art techniques which integrate basic breast stem cell biology with exposure assessment,
environmental epidemiology, and toxicology. We expect that the findings from this study will provide significant
impact for reduction of TNBC incidence and mortality by defining the factors that cause TNBC disparities,
providing actionable targets for precision breast cancer prevention.

## Key facts

- **NIH application ID:** 10076830
- **Project number:** 5R01ES028802-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Justin Adam Colacino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,207
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076830

## Citation

> US National Institutes of Health, RePORTER application 10076830, Developmental Exposures, Stem Cell Reprogramming, and Breast Cancer Disparties (5R01ES028802-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10076830. Licensed CC0.

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