# Nephron Sub-segmental Omics and Quantitative 3D Imaging of Human Kidney.

> **NIH NIH UH3** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $679,109

## Abstract

There is a fundamental gap in understanding the mechanisms that determine progression in human kidney
disease. The long term goal is to characterize key cellular and molecular pathways regulating progression of
acute and chronic kidney diseases (AKI and CKD), to identify novel markers that assess disease progression,
and to develop specific therapeutic interventions targeting these pathways. The cross-talk between tubular
subsegments and immune cells in the kidney is an important determinant of fibrosis and disease progression.
Consequently, the objective of this application is to selectively examine the transcriptome of tubular
subsegments and to quantify and localize immune cell subtypes in relation to tubular subsegments and renal
structures in patients with AKI and CKD. The central hypothesis of this application is that the transcriptome of
kidney tubular subsegments and the abundance and distribution of immune cell subtypes are unique and
complimentary identifiers of disease progression in human kidney diseases. The rationale for the proposed
research is that once the unique molecular and cellular identifiers that correlate with disease progression and
long term outcomes are determined, they can be used to monitor efficacy of pharmacologic interventions,
identify animal models that best represent human disease for translational research, and reveal novel
approaches towards treating these conditions. The central hypothesis will be tested by pursuing three specific
aims: 1) Define the transcriptome expressed by the tubular subsegments from biopsies of patients with AKI
and CKD and correlate molecular signatures with clinical outcome. 2) Determine the abundance and
distribution of immune cell subtypes in the same set of patient biopsies. 3) Backmap key molecular pathways
to the renal biopsy in order to define molecular, cellular and structural correlations. Under the first aim, laser
microdissection of tubular subsegments will be performed on biobanked kidney biopsies from case-matched
patients with AKI and CKD that rapidly progressed and those that did not rapidly progress. Gene expression
analysis will be performed on RNA isolated from the tubular subsegments to discern the transcriptomic
signature of tubular subsegments. Under the second aim, advanced three-dimensional (3-D) tissue cytometry
will be performed on the biobanked kidney biopsies from the same case-matched patients described in the first
aim to quantify the immune cell composition, examine spatial cellular organization, and delineate detailed
morphologic differences in patients who rapidly progressed and those who did not rapidly progress. In the third
aim, we will stain for key molecular pathways in order to create a large-scale digital model of the human biopsy
that highlights molecular, cellular and structural correlations important for disease pathophysiology and
progression. The proposed research is significant, because it is the next step in a continuum of research that is
...

## Key facts

- **NIH application ID:** 10242708
- **Project number:** 5UH3DK114923-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Tarek Maurice Ashkar
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $679,109
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242708

## Citation

> US National Institutes of Health, RePORTER application 10242708, Nephron Sub-segmental Omics and Quantitative 3D Imaging of Human Kidney. (5UH3DK114923-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242708. Licensed CC0.

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