# Modulating purine metabolism to treat kidney injury in sepsis.

> **NIH NIH K08** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $129,299

## Abstract

Project Summary/Abstract
Candidate and environment: Takashi Hato, MD is Assistant Professor of Medicine in the Division of
Nephrology at Indiana University School of Medicine. The applicant's long-term goal is to become a physician
scientist with a focus on the discovery of targeted therapies for acute kidney injury. The primary goal of his K08
proposal is to provide insight into the role of purine metabolism in sepsis-induced acute kidney injury. The
applicant plans on extending the work in his future studies with the ultimate goal to harness this metabolic
pathway to control energy and second messenger system for renal protection. Dr. Pierre Dagher, Professor of
Medicine, is an accomplished physician scientist specializing in acute kidney injury. Dr. Dagher has been the
applicant's primary mentor since his nephrology fellowship training and will serve as the primary mentor during
the course of this award.
Research: Sepsis remains the leading cause of death in hospitalized patients. The survival rate further
deteriorates when sepsis is complicated by acute kidney injury. There is a critical need to identify novel
therapeutic approaches to treat sepsis and its grave sequelae. For this proposal, Dr. Hato and his team have
performed unbiased metabolomics and transcriptomics analyses and found that purine metabolism is severely
deranged in the septic kidneys. Sepsis resulted in significant depletion of purine nucleosides, most notably
guanosine. Their preliminary work also revealed that exogenous guanosine supplementation could modulate
multiple genes involved in the purine metabolism pathway and limit kidney injury. The beneficial role of
guanosine in sepsis is largely unknown. It is therefore the primary goal of this application to investigate the
mechanisms of guanosine-mediated renal protection. They hypothesize that the protective effects of guanosine
are medicated by positive reprograming of renal purine metabolism at the gene level. A combination of tools
will be used including intravital microscopy, in vivo siRNA technology, microdissection and isotope tracing to
investigate the mechanisms of guanosine action at the cellular and molecular levels without compromising in
vivo significance.

## Key facts

- **NIH application ID:** 10155474
- **Project number:** 5K08DK113223-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Takashi Hato
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $129,299
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155474

## Citation

> US National Institutes of Health, RePORTER application 10155474, Modulating purine metabolism to treat kidney injury in sepsis. (5K08DK113223-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155474. Licensed CC0.

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