# Pax2 Interacting Proteins in Development and Disease

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $584,724

## Abstract

ABSTRACT
This competitive renewal application investigates how critical genes and pathways that determine renal
epithelial cell differentiation, growth, and survival contribute to normal renal physiology and recovery from
acute kidney injury. During previous funding periods, we have made significant breakthroughs in defining the
mechanisms of Pax2 protein function in development and disease. Interactions between Pax proteins and
epigenetic writers can imprint epithelial specific fates during development. In adults, the related gene Pax8 is
expressed in all epithelial cells, whereas Pax2 is restricted to collecting ducts in the inner and outer medulla.
How these two proteins function redundantly to control urine concentration and water resorption in the medulla
will be defined using genetic, whole genomic, and cell biological methods. Preliminary data strongly indicate
an essential role of Pax2/8 for the expression of urea, water, and ion channels. Furthermore, the function of
Pax2 and Pax8 in recovery form acute renal injury will be examined in targeted mutants and animal model of
ischemia reperfusion and nephrotoxicity. We propose that Pax genes are central to driving recovery in
proximal tubules by promoting dedifferentiation of surviving cells, re-entry into mitosis, and resetting of
epigenetic marks essential for maintaining a renal cell phenotype. Whole genome and transcriptome analyses,
coupled to single cell methods, will delineate specific genes and pathways activated and repressed by Pax
proteins during recovery such that novel potential targets for therapy may be illuminated.

## Key facts

- **NIH application ID:** 10404077
- **Project number:** 5R01DK054740-22
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gregory R Dressler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $584,724
- **Award type:** 5
- **Project period:** 1999-01-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404077

## Citation

> US National Institutes of Health, RePORTER application 10404077, Pax2 Interacting Proteins in Development and Disease (5R01DK054740-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10404077. Licensed CC0.

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