# Role of Calpains in Podocyte Biology

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $368,500

## Abstract

Project Summary
Chronic kidney disease (CKD) often leads to irreversible deterioration of kidney function that often progresses
to End Stage Kidney Disease (ESKD). CKD has emerged as a serious public health issue and data obtained
from the USRDS reveals that the number 20 million patients in the United States suffer from CKD. As
glomerular diseases secondary to podocyte dysfunction account for greater than 80% of all CKD, an intensive
molecular and genetic approach to identify mechanisms for podocyte development, maintenance and repair
may provide new therapeutic targets Recent evidence suggests an important role of glomerular injury
exacerbated by calpain activation. Using a unbiased screen, we have identified Pfn1, as potentially a critical
gene to maintain the integrity of the glomerular filtration barrier. Loss of PFN1 in human podocytes resulted in
multinucleated cells, increased calcium, and calpain 2 activation. Therefore, In Aim 1, we will define the
fundamental mechanisms on how loss of Pfn1 contributes to podocyte dysfunction through characterizing the
new generated knockout mice. In Aim 2, we will characterize the role of Capn2 to stabilize podocyte function
and further investigate the link between Pfn1 and Capn2. Our mouse models of disease provide impetus to
further define the role of Pfn1 and Capn2 in the formation and maintenance an intact glomerular filtration
barrier.

## Key facts

- **NIH application ID:** 10609403
- **Project number:** 5R01DK083294-13
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Shuta Ishibe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $368,500
- **Award type:** 5
- **Project period:** 2010-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609403

## Citation

> US National Institutes of Health, RePORTER application 10609403, Role of Calpains in Podocyte Biology (5R01DK083294-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10609403. Licensed CC0.

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