# Genomic and functional investigations of the transcriptional regulatory network of salivary gland morphogenesis and stem cell fate choices in defined genetic models

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $377,567

## Abstract

PROJECT SUMMARY
 The intricate and dynamic balance between self-renewal, proliferation and differentiation of
stem/progenitor cells of the salivary gland (SG) must be tightly regulated to ensure proper morphogenesis,
homeostasis and regeneration. Alterations to normal SG function, clinically often manifested with
hyposalivation, are associated with diseases such as Ectodermal Dysplasias, Sjögren’s Syndrome and with γ-
irradiation therapy of oral cancer patients. Currently, treatment options for hyposalivation remain limited.
Therefore, identifying crucial transcriptional and signaling networks that govern stem/progenitor cell function of
the SG are much needed to facilitate targeted stem cell and regenerative-based therapies. ΔNp63, a stem cell
enriched transcription factor, plays a critical role in epithelial regenerative function as evident from the
phenotype of ΔNp63-null animals which exhibit developmental arrest and agenesis of epithelial-rich organs
including the SG. However, our current knowledge of the molecular mechanisms by which ΔNp63 directs gene
expression programs necessary for the commitment, maintenance and differentiation of the stem/progenitor
cell population in the SG is lacking. Thus, identifying the p63-driven regulatory networks, particularly in the
global and genomic context, is a key step towards a better understanding of the biology of SG stem/progenitor
cells and ultimately in directing new strategies in treating SG dysfunction. To address these knowledge gaps,
we will utilize multiple versatile mouse models to study two major independent areas of interest. First, we will
use conditional knockout mouse models to examine the role of ΔNp63 in SG morphogenesis and in adult
tissue maintenance and repair (Aim1). Such systematic studies are much needed as they will identify for the
first time, the functional role of p63 in SG development and in orchestrating stem/progenitor cell differentiation
programs. Second, we will use p63 knockout mouse models and lineage tracing experiments to determine the
contribution of p63+ stem and progenitor cells during SG regeneration and in response to irradiation induced
damage. Furthermore, we will define p63 dependent SG cellular identities and the defined cellular and
molecular signature that is associated with regeneration and in response to irradiation by performing single cell
RNA-sequencing (Aim2). These studies will better elucidate the role of ΔNp63 in SG organogenesis, and adult
gland maintenance, and elucidate its contribution towards SG regeneration and in response to irradiation
induced injury. Importantly, our genetic and genomic studies will also uncover novel ΔNp63-pathways
dependent and independent biomarkers and drivers of the distinct cell states associated with regeneration and
radiosensitivity. Long term, knowledge garnered from our proposed mechanistic studies will have clinical and
therapeutic implications for human patients who suffer from SG dysfunction diseases.

## Key facts

- **NIH application ID:** 9875451
- **Project number:** 5R01DE027660-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Rose-Anne Romano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,567
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875451

## Citation

> US National Institutes of Health, RePORTER application 9875451, Genomic and functional investigations of the transcriptional regulatory network of salivary gland morphogenesis and stem cell fate choices in defined genetic models (5R01DE027660-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9875451. Licensed CC0.

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