# The role of neutral ceramidase in acute kidney injury and its progression to chronic kidney disease.

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $501,565

## Abstract

Summary:
The long-term goal of this proposal is to develop novel therapeutics for a serious unmet medical need, namely
acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) for which there are no treatments
other than supportive care. The mechanisms of kidney injury and its progression to CKD are largely unknown
and this proposal aims to fill some of these knowledge gaps. The short-term goal of this proposal is to validate
a novel target for treating AKI and its progression to CKD for future drug development. This target is neutral
ceramidase (NCD), an enzyme involved in metabolism of the sphingolipid ceramide. The proposal is based on
a strong foundation of supporting preliminary data that indicates that mice lacking NCD are protected in models
of AKI and CKD and in vitro data indicating that deletion or inhibition of NCD increases autophagy and protects
cells from a variety of cellular stresses. Thus, this proposal will test the hypothesis that deletion or inhibition of
NCD confers protection from AKI and injury-induced CKD via upregulation of autophagy. We will test this
hypothesis with three interrelated but independent specific aims that will (1) determine the mechanism of
protection of kidney cells in vitro from cellular stress when NCD is deleted or inhibited; (2) determine the role of
NCD in AKI; and (3) determine the role of NCD in kidney injury progression to CKD. Data obtained in this proposal
will provide many scientific and translational advances that are essential for achieving our long-term goal of
developing therapeutics for this unmet medical need.

## Key facts

- **NIH application ID:** 10084295
- **Project number:** 5R01DK124112-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** LEAH J SISKIND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $501,565
- **Award type:** 5
- **Project period:** 2020-01-10 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084295

## Citation

> US National Institutes of Health, RePORTER application 10084295, The role of neutral ceramidase in acute kidney injury and its progression to chronic kidney disease. (5R01DK124112-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10084295. Licensed CC0.

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