# Specifying the Renal Epithelial Phenotype in Development and Disease

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $52,358

## Abstract

ABSTRACT
Specifying the Renal Epithelial Phenotype in Development and Disease.
This application investigates the genetic and biochemical control of renal function in adults, with particular
emphasis on urine concentration and the function of Pax proteins. The Dressler Lab has developed genetically
engineered mouse lines and epithelia cell derivatives that can delete either Pax2, Pax8, or both genes and
their protein products. These Pax proteins are critical for the development of the nephrons, but their functions
in adult terminally differentiated epithelia has not been studied. Preliminary data show a significant effect on
water, urea, and sodium transporters in adult kidneys upon deletion of both Pax proteins. These data suggest
a transcriptional or maintenance role for Pax genes in renal epithelial cells that will be characterized at multiple
levels. How Pax proteins impact promoters and enhancers, modify and maintain patterns of histone
methylation, and activate or repress target gene transcription will be studied in vivo and in cell culture models.
Direct targets of Pax proteins will be identified by chromatin precipitation and bioinformatic analyses. Whether
the related proteins Pax2 and Pax8 have redundant functions in the collecting ducts and renal medulla will be
determined by individual single and double mutants. How Pax proteins specify the genomic landscape by
recruiting histone methyltransferase complexes will also be studied in cell cultures that can delete either or
both proteins in response to tamoxifen. These studies will determine fundamental regulatory mechanisms
governing renal function and epithelial cell specification, and can identify new pathways for intervention to
address both chronic and acute renal disease.

## Key facts

- **NIH application ID:** 10112101
- **Project number:** 5F32DK121469-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ann Laszczyk
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $52,358
- **Award type:** 5
- **Project period:** 2020-03-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112101

## Citation

> US National Institutes of Health, RePORTER application 10112101, Specifying the Renal Epithelial Phenotype in Development and Disease (5F32DK121469-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10112101. Licensed CC0.

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