# Transcriptional Programming in the Maintenance and Commitment of Nephron Progenitors

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $46,036

## Abstract

PROJECT ABSTRACT
Approximately 4.9 million adults in the US suffer from kidney disease. Current therapies do not provide curative
treatments for end state renal disease. Regenerative nephrology holds promise for developing novel therapeutic
strategies. The functional unit of the kidney is the nephron, which is derived from a distinct progenitor cell
population during embryonic development. A delicate balance of nephron progenitor cell (NPC) self-renewal and
differentiation is required to generate a species-appropriate number of nephrons during the course of kidney
development. The transcriptional regulator Six2, and transcriptional mediators of the Wnt/β-catenin signaling
pathway, Lef/Tcf factors, play critical roles balancing the maintenance and commitment of NPCs. In this, Six2 is
essential for NPC self-renewal and interacts with Lef/Tcf factors. β-catenin accumulation acts to switch the code
of Lef/Tcf factor engagement at differentiation targets from a repressor to activator transcriptional signature. The
overarching hypothesis tested in this proposal is that β-catenin accumulation switches the Lef/Tcf regulatory
signature from an OFF to ON state. In AIM 1, I will perform loss of function experiments to unravel the mechanism
of action of β-catenin concentration dependent Tcf/Lef factor engagement resulting in transcriptional changes.
In AIM 2, I will perform multi-protein proteomic analysis to define multiprotein complexes surrounding β-catenin
with immunoprecipitation and mass spectrometry-based affinity proteomics Mechanistic understanding of
Wnt/β-catenin signaling in concert with identified binding partners will facilitate the derivation of nephron-like cell
types in vitro and ultimately regenerative therapies for renal diseases.

## Key facts

- **NIH application ID:** 10212379
- **Project number:** 5F31DK122777-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Helena Bugacov
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212379

## Citation

> US National Institutes of Health, RePORTER application 10212379, Transcriptional Programming in the Maintenance and Commitment of Nephron Progenitors (5F31DK122777-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212379. Licensed CC0.

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