# Understanding Lrig1+ in vocal fold epithelium and organoid biology

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $540,430

## Abstract

Project Summary/Abstract:
Voice dysfunction impairs the quality of life of affected patients and treating these disorders is associated with
substantial and far-ranging social, psychological, and economic costs. Vocal fold (VF) inflammatory lesions
cause common voice disorders related to disrupted epithelial homeostasis accompanied by inflammatory
infiltrates and changes in the lamina propria. In studies of the epithelium from elsewhere in the body, cell types
that originate hyperplasic changes are epithelial stem cells. These cells have the capability to self-renew and
give rise to the progeny of differentiated daughter cells which is regulated by the local microenvironment and
cell-autonomously via Notch signaling. Inactivation of Notch1 in the presence of inflammatory cytokines can
lead to epithelial hyperplasia, which can be modeled using in vitro organoids. The overall objective of this
proposal is to provide a comprehensive characterization of VF epithelial stem cells, their requirements for self-
renewal and differentiation under physiological conditions and in response to stress factors, namely injury and
mechanical load, while also creating VF organoids to elucidate molecular mechanisms that underline aberrant
epithelial remodeling as seen in benign inflammatory VF lesions. To achieve our goal we will genetically label
epithelial stem cells targeting the Lrig1 gene that has been linked to stemness properties in majority of epithelia
and our preliminary data show that Lrig1 is also expressed in human and murine VF epithelial cells. In Aim 1,
we will perform transcriptome profiling of murine and human VF Lrig1 cells and measure Lrig1 cell responses
to mechanical load during homeostasis. We will delineate the mechanistic role of murine Lrig1 cells in
homeostasis, and genetically inactivate Notch1 in murine Lrig1 cells to determine its effect on proliferation and
differentiation in vivo. In Aim 2, we will induce VF epithelial injury in a murine model, perform transcriptome
profiling of murine Lrig1 cells and measure their responses to mechanical load during epithelial recovery. We
will determine the functional role of murine Lrig1 cells and Notch1 signaling in re-epithelization. In Aim 3, we
will determine differentiation potential of murine and human VF Lrig1 cells using in vivo subrenal graft assay
and in vitro organoids. We will utilize VF organoids to model Notch-mediated epithelial hyperplasia using
genetic, pharmacologic approaches, and inflammatory cytokines. We will create a reliable culture system that
will improve our understanding of VF epithelial cell biology related to VF inflammatory lesions in the context of
personalized medicine.

## Key facts

- **NIH application ID:** 10872155
- **Project number:** 5R01DC020734-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Vlasta Lungova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $540,430
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872155

## Citation

> US National Institutes of Health, RePORTER application 10872155, Understanding Lrig1+ in vocal fold epithelium and organoid biology (5R01DC020734-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10872155. Licensed CC0.

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