# Regulation of acute kidney injury to Candida albicans by b-catenin/TCF pathway

> **NIH NIH R21** · AUGUSTA UNIVERSITY · 2021 · $231,000

## Abstract

Summary: Candida albicans infection is the third most common infection in hospitalized patients, with a
mortality rate ranging between 14.5%–49%. Disseminated candidiasis causes kidney failure resulting in
severe morbidity of the immunocompromised host such as those with acquired immune deficiency syndrome
or cancer, organ or bone marrow transplant patients, or patients taking immunosuppressant drugs an extended
period of time. Prevention and treatment of disseminated candidiasis are an important clinical problem, and
currently, there are no approved vaccines against any fungal pathogens. However, the cellular and molecular
mechanisms underlying renal failure caused by pathogenic Candida albicans infection remain largely unknown.
The immune system plays an important role in protecting against disseminated candidiasis. Immune activating
pathways in renal antigen-presenting cells (APCs) play a critical role in inducing robust immune responses in
the kidney against C. albicans. In contrast, the anti-inflammatory pathways in APCs suppress immune
responses in the kidney against C. albicans and increasing susceptibility to kidney damage and failure. Thus,
identifying the signaling pathways that program APCs towards an immunogenic state versus a regulatory state
will help identify new targets for therapeutic manipulation of immune cells that augments kidney immunity
against Candida albicans and protects against infection-associated-kidney damage and failure. We have
identified a new and previously unsuspected role for β-catenin and TCF4 as a key molecular anti-inflammatory
pathway in APCs that is critical for suppressing immune responses against disseminated candidiasis, causing
increased susceptibility to kidney damage and failure. This application aims to delineate the molecular
mechanisms by which β-catenin and TCF4 metabolically program renal APCs against disseminated
candidiasis and its impact on kidney function.

## Key facts

- **NIH application ID:** 10373167
- **Project number:** 1R21AI156103-01A1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Santhakumar Manicassamy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373167

## Citation

> US National Institutes of Health, RePORTER application 10373167, Regulation of acute kidney injury to Candida albicans by b-catenin/TCF pathway (1R21AI156103-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10373167. Licensed CC0.

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