# Bridging the gap of late gestation human nephrogenesis using a non-human primate model

> **NIH NIH K08** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $165,780

## Abstract

Project Summary
Premature infants have low nephron number (endowment) and are at high risk for chronic kidney disease (CKD)
and end stage renal disease as adults. Most nephrons are added late in gestation through a poorly understood
process called lateral branch nephrogenesis (LBN). As direct study of late gestation human kidney development
is difficult, the non-human primate model (rhesus macaque) was recently identified as a suitable model to bridge
this knowledge gap. The long-term goal is to apply the molecular findings of LBN in the non-human primate
model towards development of therapeutic methods aimed at extending nephrogenesis in preterm infants. The
central hypothesis is that a shift in the signaling milieu involving components of the developing kidney (nephron
progenitor cells (NPC), ureteric bud (UB), and stroma) results in sustaining LBN over multiple weeks in late
gestation. The rationale for this proposed research is that the genetically tractable non-human primate model
system can be used to test hypotheses and apply therapeutic interventions aimed at improving human nephron
endowment. The central hypothesis will be tested by using the latest molecular technologies to understand the
molecular mechanism sustaining LBN in the non-human primate, including single-cell RNA sequencing, laser
capture microdissection with RNA sequencing, single-nucleus RNA sequencing, and single-nucleus ATAC
sequencing. Preliminary morphologic study on the postnatal day two marmoset kidney identified a single ureteric
stalk with lateral branches consistent with LBN, suggesting the common marmoset could be used as a genetically
tractable primate model. Expected outcomes include assembly of the largest primate late gestation developing
kidney molecular dataset and identification of genes and pathways enriched and regulatory networks active
during LBN, as well as identification of a genetically tractable model to study LBN to understand why prematurity
leads to early cessation of nephrogenesis in humans, and how to extend it. These results are expected to have
a positive impact on the current understanding of late gestation human nephrogenesis by identifying molecular
pathways and potential therapeutic interventions for those born prematurely. In addition to the aims outlined in
this proposal, career development plans include didactic training in molecular biology and bioinformatics through
the Certificate program in Bioinformatics, wet-lab experience with the latest molecular technologies and multi-
omic platforms, and career advancement through a selected advisory committee for transition to independence
and submission of R01 during the K08 award period.

## Key facts

- **NIH application ID:** 10909239
- **Project number:** 5K08DK131259-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Meredith Schuh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $165,780
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909239

## Citation

> US National Institutes of Health, RePORTER application 10909239, Bridging the gap of late gestation human nephrogenesis using a non-human primate model (5K08DK131259-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10909239. Licensed CC0.

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