# Elucidating novel mechanisms in the pathogenesis of Alport syndrome

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $424,278

## Abstract

PROJECT ABSTRACT
Alport syndrome is the second most common cause of hereditary chronic kidney disease and is
caused by mutations in the type IV collagen genes encoding 3, 4 and 5 chains. X-linked Alport
syndrome (XLAS) accounts for most cases and is caused by mutations of the 5 chain. Therapies
to slow the progression of XLAS are limited and affected males invariably progress to end stage
kidney disease. The disease is known to affect glomeruli: the 3, 4 and 5 (IV) chains are
deposited by podocytes into the glomerular basement membrane, and patients with Alport
syndrome have structural defects in the glomerular basement membrane that causes hematuria
and proteinuria. Despite this, there are major gaps in our understanding of disease pathogenesis.
It is known that other cell types in the kidney produce 3, 4 and 5 chains, but to date, their
function and the role they play in tubule function and disease pathogenesis has been unexplored.
Based on preliminary studies, we hypothesize that 5 from non-glomerular cells is required for
normal cell function and shape, and that the non-glomerular cell abnormalities contribute
substantially to the clinical presentation and pathogenesis of XLAS. We therefore propose to 1)
identify the glomerular and non-glomerular contributions to XLAS pathogenesis and progression,
2) establish the function(s) of 5 in tubular cells, including elucidating signaling pathways that
underlie its role in tubular cells. Together, these studies will generate resources to study type IV
collagen function and will greatly advance knowledge of the pathogenesis of XLAS. We expect
they may also pave the way for future studies that lead to the development of novel therapeutic
strategies.

## Key facts

- **NIH application ID:** 11028068
- **Project number:** 1R01DK141873-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DENISE K MARCIANO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $424,278
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11028068

## Citation

> US National Institutes of Health, RePORTER application 11028068, Elucidating novel mechanisms in the pathogenesis of Alport syndrome (1R01DK141873-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11028068. Licensed CC0.

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