# Epithelial cell-cell junction remodeling in response to cell- and tissue-scale forces

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $246,130

## Abstract

PROJECT SUMMARY / ABSTRACT
The overarching goal in my lab is to identify mechanisms that promote maintenance, reinforcement, and
remodeling of cell-cell adhesion and barrier function in response to cell-scale and tissue-scale forces. Epithelial
cell-cell junctions including adherens junctions, tight junctions, and tricellular junctions adhere epithelial cells to
one another, transmit forces between cells, and generate barrier function that selectively regulates what can
pass in the paracellular space between cells. Each of these cell-cell junctions is connected to a contractile apical
actomyosin array, and the connections between junctional proteins and the cytoskeleton are highly dynamic.
Cells sense their mechanical environment as mechanical forces challenge cell-cell junctions – from cell-scale
forces like a dividing cell pulling on its neighbors, to tissue-scale forces like morphogenesis sculpting the
organism. Epithelial cells modulate their cell-cell junctions and connections to the actin cytoskeleton to ensure a
stable yet adaptable architecture. My group seeks to understand how signaling proteins like Rho GTPases,
RhoGEFs & RhoGAPs, scaffolding proteins, mechanosensitive proteins, calcium, and the cytoskeleton work
together to create a strong but flexible epithelial barrier. We use developing Xenopus laevis embryos as a model
for the vertebrate epithelium, an array of innovative molecular tools for live microscopy of key molecular players,
a live imaging barrier assay developed in our lab, and several approaches to mechanically challenge the
epithelium either globally or locally. The major research themes of this R35 MIRA are: 1) “Rho flare-mediated
tight junction remodeling” where we will address the question: What are the signaling pathways that promote
tight junction repair when tight junctions are damaged as cells change shape? 2) “Mechanics of epithelial
cytokinesis” where we will address the question: How do cells neighboring the dividing cell contribute to
maintenance of adhesion and barrier function during epithelial cytokinesis? 3) “Tension transmission & signaling
at tricellular junctions” where we will address the question: How are tricellular junctions reinforced and remodeled
when mechanically challenged? By pursuing these research goals over the next five years, my group will
discover novel mechanisms that promote maintenance, reinforcement, and remodeling of cell-cell junctions and
their cytoskeletal connections in response to physiological mechanical forces.

## Key facts

- **NIH application ID:** 10840638
- **Project number:** 1R35GM153204-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ann Louise Miller
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,130
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840638

## Citation

> US National Institutes of Health, RePORTER application 10840638, Epithelial cell-cell junction remodeling in response to cell- and tissue-scale forces (1R35GM153204-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10840638. Licensed CC0.

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