# Unanticipated roles of C5aR1 Signaling Leading from Acute to Chronic Kidney Disease

> **NIH NIH K08** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $164,204

## Abstract

Project Summary: Chronic kidney disease (CKD) continues to be a significant factor in global morbidity and
mortality. Patients experiencing repetitive acute kidney injury (AKI) are predisposed to CKD. Despite
discoveries of novel biomarkers and increasing awareness of kidney health, the prevalence of CKD and end-
stage kidney disease (ESKD) continues to rise. To date, the lack of therapeutic options halting progression
from AKI to CKD still represents an unmet need. Our preliminary data suggest while activation of complement
component 5 receptor 1 (C5aR1) promotes renal tubular epithelial cell (RTEC) damage, C5aR1 signaling on
myeloid cells may confer renoprotective effects ameliorating AKI. This project will determine the roles of C5a-
C5aR1 axis activation in 1) RTEC cellular senescence and kidney fibrosis (Aim 1), and in 2) myeloid cells
responsible for AKI pathogenesis (Aim 2). These aims will test our central hypothesis that C5aR1 activation in
kidney resident macrophage (KRM) mitigates the acute phase of AKI, whereas C5a-C5aR1 signaling in RTEC
mediates their cellular senescence with subsequent CKD progression and fibrosis. Our findings will lay the
fundamental knowledge of the potential clinical use of complement-regulating therapies for kidney
diseases. Candidate and Training: The primary objective of this application is to support Dr. Mon-Wei (Sam)
Yu's career development into an independent basic scientist in the fields of complement biology and kidney
diseases by using novel murine models and immunological approaches. Dr. Yu's proposed training activities
are in four areas: 1) Establish innovative scientific questions and design appropriate experiments to answer
those questions; 2) Attain the necessary techniques, especially in the immunology field, to perform
experiments; 3) Gain training and experiences for big data analysis, and 4) Refine the skills for grantsmanship
and manuscript preparation. Environment: Division of Nephrology at Mount Sinai Hospital and the Icahn
School of Medicine at Mount Sinai (ISMMS) are fully committed to junior faculty career and scientific
development. Dr. Paolo Cravedi and Dr. John Cijiang He (Division Chief) are renowned experts in complement
and tubular biology with a strong K Award trainees track record.

## Key facts

- **NIH application ID:** 10817002
- **Project number:** 5K08DK132501-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Mon-Wei Yu
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $164,204
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817002

## Citation

> US National Institutes of Health, RePORTER application 10817002, Unanticipated roles of C5aR1 Signaling Leading from Acute to Chronic Kidney Disease (5K08DK132501-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817002. Licensed CC0.

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