# The Contribution of Ribonuclease 7 to Urinary Tract Anitbacterial Defense

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2022 · $484,792

## Abstract

ABSTRACT
Urinary tract infections (UTIs), including pyelonephritis, are among the most common and serious infections encountered
in clinical practice. No proven treatment options exist to prevent UTI. New strategies are needed to augment the ability of
host defenses to prevent UTI and minimize UTI-associated morbidity. A growing body of evidence, from our laboratory
and others suggests that antimicrobial peptides (AMP), an essential component of the innate immune response, protect the
urinary tract from invasive bacterial infection. Our research team has identified Ribonuclease 7 (RNase 7) as a potent and
highly abundant human AMP that shields the urothelium from uropathogenic E. coli (UPEC). Our published data suggest
that RNase 7 is an ideal AMP to develop as a UTI therapeutic because: (A) it has potent antibacterial activity; (B) it is
highly abundant in the urinary tract; (C) it is produced by cell types that are targeted by UPEC; and (D) it has minimal
toxicity. Our emerging data suggest that RNase 7 induction shields the urothelium from UPEC, while suppressed RNase 7
production renders it susceptible to pathogens. Together, these findings provide strong support to our central hypothesis
that RNase 7 is biologically necessary to maintain urine sterility and prevent UTI. Our current understanding of RNase
7's effects on innate defenses is limited in vivo because its expression is absent in the laboratory mouse and restricted to
higher order vertebrates and humans. To fill this key knowledge gap, we developed two novel humanized RNase 7 mouse
models. These models will be used to complete our overall objective of this application, which is to further investigate the
essential contributions of RNase 7 to urine sterility. To test our central hypothesis, we will evaluate how cell-specific
RNase 7 expression impacts UTI risk in vivo using a novel Rosa26 knock-in mouse (Aim 1). In Aim 2, we will investigate
the molecular mechanisms that regulate RNase 7 expression using a novel humanized transgenic mouse that expresses
RNase 7 under the control of its own promoter. In Aim 3, we will evaluate how human genetic polymorphisms affect
RNase 7 expression and antimicrobial activity. Completion of the proposed Aims will further define the necessary
contributions of RNase 7 to urine sterility and may provide the foundation to develop RNase 7 as a novel therapeutic that
improves UTI outcomes. Given the clinical impact of UTI, in an era of emerging antibiotic resistant uropathogens,
identifying mechanisms to develop RNase 7 as a new UTI therapy may have significant benefits to public health.

## Key facts

- **NIH application ID:** 10348147
- **Project number:** 5R01DK115737-05
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** John David Spencer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $484,792
- **Award type:** 5
- **Project period:** 2018-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348147

## Citation

> US National Institutes of Health, RePORTER application 10348147, The Contribution of Ribonuclease 7 to Urinary Tract Anitbacterial Defense (5R01DK115737-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10348147. Licensed CC0.

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