# Modeling Nephrotic Syndrome in Drosophila Nephrocytes

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $347,625

## Abstract

PROJECT SUMMARY/ABSTRACT:
Nephrotic syndrome (NS) is one of the most frequent causes of End-Stage Renal Disease (ESRD) in children
and young adults, but effective treatment is lacking, particularly for Steroid-Resistant Nephrotic Syndrome
(SRNS). Rapid advances in DNA sequencing technology have led to the identification of large numbers of
genetic variants that are potential causal factors for SRNS. However, lack of in vivo functional data for these
candidate SRNS genes and their variants make it difficult to validate their roles in causing the disease. An
animal model that carry the exact mutation found in patients for disease mechanism studies and testing of
potential targeted therapies is in great demand. We have established a low-cost, high-efficiency Drosophila
model system to generate essential functional data for candidate NS genes and variants, and to expedite the
identification of novel NS genes. This novel kidney disease model system exploits the remarkable molecular,
structural and functional equivalencies of Drosophila nephrocytes and human podocytes. We studied 40 known
NS genes in nephrocytes and found that 85% of these genes play conserved roles in kidney cells from flies to
humans. We also discovered underlying disease mechanisms by generating personalized fly NS models in
which endogenous fly genes were functionally replaced by human homologs carrying patient-derived
mutations. We also developed drug testing platform using these fly NS models, and successfully reversed the
renal phenotype using targeted therapy informed by disease mechanism. In this renew proposal, we will use
the powerful genetic tools in Drosophila to identify new renal genes involved in autophagy and cytoskeleton
regulation. We will identify new nephrocyte cytoskeleton markers and components. We will also develop new
personalized Drosophila models for candidate NS genes and novel genetic variants for known NS genes, as
well as using the fly models to test potential targeted therapies. Our studies will provide the kidney disease
research community with a low-cost high-efficiency model system to functionally validate NS associated genes
and genetic variants, to identify novel NS genes, and to develop mechanism-based targeted therapies.

## Key facts

- **NIH application ID:** 10457321
- **Project number:** 5R01DK098410-10
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** ZHE HAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,625
- **Award type:** 5
- **Project period:** 2014-04-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457321

## Citation

> US National Institutes of Health, RePORTER application 10457321, Modeling Nephrotic Syndrome in Drosophila Nephrocytes (5R01DK098410-10). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10457321. Licensed CC0.

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