# Determining the role of afadin in tubular development and maintenance in the kidney

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $51,752

## Abstract

Project Summary/Abstract
Chronic kidney disease (CKD) poses an important global disease burden with limited therapeutic options. Novel
therapeutic strategies to improve renal function include implanting patient-derived kidney organoids onto the
native kidneys. However, an inability to connect organoid tubules with the host’s kidney tubules presents a major
problem that remains to be solved. Currently, the molecular mechanisms driving interconnection between tubules
and their lumens are poorly understood. Filling this gap in knowledge is critical to advance work with implantable
renal replacement tissues. Our previous studies have shown that mice lacking afadin, a cytoskeletal scaffolding
protein, from renal epithelial tubules, have a defect in lumen continuity. The goal of this project is to determine
how lumen connection/fusion occurs within tubules and determine the molecular mechanism by which afadin
promotes lumen fusion and maintenance in renal epithelia. We hypothesize that lumen fusion requires cellular
rearrangements and that these are facilitated by afadin-mediated regulation of cell-cell contacts. Here, I propose
to use well-defined in vitro and in vivo models to: (1) Determine the mechanism of lumen fusion after the onset
of de novo lumenogenesis, (2) Identify the afadin domains required for lumen fusion, and (3) Determine the role
of afadin in lumen maintenance in vitro and in an in vivo inducible knockout mouse model. The knowledge
obtained from these studies will enable a better design of epithelial structures that have the ability to form and
maintain a continuous lumen for future use as implantable therapeutics.

## Key facts

- **NIH application ID:** 10543403
- **Project number:** 5F31DK129031-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Isabel A Alejandra Lopez-Garcia
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543403

## Citation

> US National Institutes of Health, RePORTER application 10543403, Determining the role of afadin in tubular development and maintenance in the kidney (5F31DK129031-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10543403. Licensed CC0.

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