# KLF4 and WNT5A in esophageal epithelial differentiation and stratification

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $365,344

## Abstract

PROJECT SUMMARY
In this application entitled “KLF4 and WNT5A in esophageal epithelial differentiation and stratification,” we seek
to define the molecular pathways of esophageal epithelial differentiation and stratification and the perturbations
of these pathways that lead to esophageal diseases. The PI is an experienced investigator and expert in the
Krüppel-like factors (KLFs), animal models of disease, and esophageal squamous cell biology, and he is
supported by a superb research team, a collegial intellectual environment, and exceptional resources and
facilities. The proposed research is highly significant, addressing the NIH mission of “seeking fundamental
knowledge about the nature and behavior of living systems” and offering the potential for translation to
esophageal disorders such as defective wound healing after injury (e.g. radiation, infection, eosinophilic
esophagitis) and diseases such as esophageal squamous cell cancer (ESCC), which together account for
considerable morbidity, mortality, and healthcare burden in the United States and throughout the world. In
complementary approaches, we will employ novel mouse models, innovative two-dimensional and three-
dimensional culture systems, and next generation sequencing approaches to test the hypothesis that KLF4 is
a key regulator of esophageal epithelial differentiation and stratification and that studies of differentiation and
stratification in normal epithelia provide the foundation for insights into how these processes are disrupted
during diseases such as ESCC. To address this hypothesis, we will pursue the following interrelated Specific
Aims: (1) We will define the pathways of normal differentiation and stratification through mechanistic studies of
KLF4 and WNT5A (a) functional interactions and (b) via CDC42 and other downstream targets; and (2) We will
delineate the molecular underpinnings of ESCC through functional studies of KLF4 and WNT5A in vitro and in
vivo. The PI and his team have expertise in all techniques proposed in this application, and all models are
currently in hand. In sum, we anticipate that these studies will provide substantial insight into the regulatory
pathways of esophageal epithelial differentiation, stratification, and carcinogenesis, offering the potential for
eventual translation of this knowledge to human esophageal diseases.

## Key facts

- **NIH application ID:** 10130516
- **Project number:** 5R01DK119314-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JONATHAN P KATZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $365,344
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130516

## Citation

> US National Institutes of Health, RePORTER application 10130516, KLF4 and WNT5A in esophageal epithelial differentiation and stratification (5R01DK119314-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10130516. Licensed CC0.

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