# Utilizing a human stem cell model of the esophagus to understand racial disparities during injury repair

> **NIH NIH K99** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $91,284

## Abstract

PROJECT SUMMARY/ABSTRACT
African Americans (AA) and European Americans (EA) have a similar prevalence of gastro-esophageal reflux
disease (GERD). Nonetheless, when compared to EA, AA show a lower incidence of esophagus damage,
metaplasia, and esophageal adenocarcinoma. Population genetics and molecular studies have implicated
specific genes for these differences in human tissue; however, a lack of racially diverse human esophagus
models hinders further investigation into the mechanisms and potential treatment options. We developed an
ancestrally diverse stem cell/organoid biobank of human esophagus and a high-content, image-based
screening assay to interrogate bile-acid injury response. Results showed that AA esophageal cells responded
significantly differently than EA-derived cells, mirroring tissue profiling and clinical findings. Furthermore, we
have previously reported that a key enzyme, glutathione-transferase theta-2 (GSTT2), is responsible for
inactivating reactive oxygen species, thus reducing DNA damage, and is highly expressed in the AA
esophagus. Utilizing the ancestrally diverse stem cell model, we show key associations of GSTT2 low levels
with higher injury, consistent with primary human tissue response to injury. However, a direct role of GSTT2 in
this response and mechanism/drugs to maintain epithelial homeostasis and fitness to esophageal cells
remains to be elucidated. Hypothesis: Esophageal tissue from African Americans respond differently to gastric
acid/bile injury due to higher expression of detoxifying enzyme GSTT2, and compounds that can stabilize
GSTT2 will protect cells against injury. The three specific aims to be investigated in this proposal will involve
primary tissue and stem cell-derived in vitro cultures to validate the molecular profiles and differences in injury
response between EA and AA cells at the single-cell level (Aim 1), with genetic manipulation of GSTT2 to
determine direct mediation of protection against injury (Aim 2), and a high-throughput unbiased
characterization of injury response coupled with a drug screen to determine compounds that will inhibit
bile/acids injury (Aim 3). Dr. Ferrer-Torres’ primary research goals in the K99.R00 program is to develop high
throughput techniques that will allow her to study ancestrally diverse populations and their response to injury.
Therefore, the K99 phase has been planned to train in stem cell genetic modifications and high-content
phenotypic-based drug discovery. For this mentored phase, Dr. Ferrer-Torres will work with Dr. Jason Spence
and co-mentor by Dr. Jonathan Sexton. The mentored K99 program has been designed for Dr. Ferrer-Torres’
gain expertise in these areas. In addition, Dr. Jules Lin and Dr. Marcia Cruz-Correa will serve as advisory
postdoctoral committee members and advisors for clinical immersions. This will be carried out utilizing the
exceptional resources available at the University of Michigan. This will impulse Dr. Ferrer-Torres’ goals and
hel...

## Key facts

- **NIH application ID:** 10514960
- **Project number:** 1K99DK133804-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Daysha Ferrer Torres
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $91,284
- **Award type:** 1
- **Project period:** 2022-06-22 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514960

## Citation

> US National Institutes of Health, RePORTER application 10514960, Utilizing a human stem cell model of the esophagus to understand racial disparities during injury repair (1K99DK133804-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10514960. Licensed CC0.

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