# Role of LRP1 in Podocyte Biology

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $421,844

## 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 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 Previous evidence has suggested the
importance of endocytic trafficking in podocytes, Using a unbiased screen, we have
unearthed Lrp1 within clathrin coated vesicles, and as a potentially important gene to
maintain the integrity of the glomerular filtration barrier. Loss of Lrp1 specifically in mice
podocytes resulted in proteinuria and progression of CKD. Therefore, In Aim 1, we will
define the fundamental mechanisms on how loss of Lrp1 contributes to podocyte
dysfunction through characterizing the newly generated knockout mice. In Aim 2, we will
determine how Lrp1 signaling plays a potential role in dsDNA repair by examining genes
critical for nonhomologous end joining Setd1a and Lig4, and test SP16, a FDA approved
Lrp1 agonist in the treatment of mouse models of glomerular injury.

## Key facts

- **NIH application ID:** 10871900
- **Project number:** 5R01DK093629-11
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Shuta Ishibe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,844
- **Award type:** 5
- **Project period:** 2012-09-27 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871900

## Citation

> US National Institutes of Health, RePORTER application 10871900, Role of LRP1 in Podocyte Biology (5R01DK093629-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10871900. Licensed CC0.

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