# GENERATING AN ATLAS OF THE DEVELOPING HUMAN URINARY OUTFLOW TRACT.

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $314,995

## Abstract

The urinary outflow tract includes the Ureteropelvic junction, Straight Ureter, Trigone, Bladder and Urethra;
structures critical for transport, storage and excretion of urine. Obstruction that blocks the flow of urine from the
kidneys to the bladder, or reflux can result in hydronephrosis, a defect commonly detected in antenatal
ultrasound that occurs in about 1% of the population. In the majority of individuals hydronephrosis will self-
resolve without causing renal damage, however in a small number of cases hydronephrosis persists and can
cause damage to the kidney and bladder. At present there is no way to distinguish between these outcomes.
Identifying mutations that lead to VUR and obstruction will be important for diagnosis and clinical management
of CAKUT, however understanding how and at which stages molecular pathways act will be essential
for validation and interpretation of new findings from genetic studies. In Aim 1, we will characterize the
process of ureter maturation in the developing human urinary tract and we will generate a temporal and spatial
Atlas of Gene expression. We will focus on genes that when mutated in mice or humans cause CAKUT in
collaboration with the Gharavi Lab. These studies will be performed as part of the GUDMAP Consortium,
and Aimed at producing an atlas of gene expression in the developing human urinary tract. The urinary
outflow tract is lined with a specialized epithelium called the urothelium that maintains a waterproof and toxin
resistant barrier that extends from the renal pelvis to the proximal urethra. The adult urothelium is one of the
most quiescent epithelia in the body, but can rapidly regenerate in response to acute injury from Urinary tract
infection (UTI) or exposure to toxins. However chronic injury caused by recurrent or persistent UTI, abnormal
sensory nerve stimulation or chemicals can permanently damage the urothelium most likely due at least in
part, to depletion of progenitor populations that normally produce superficial cells after injury. At present there
is now way to repair or regenerate the damaged urothelium The studies proposed here will produce a
molecular atlas of stromal/urothelial signaling pathways that are expressed during urothelial stratification and
define urothelial sub-populations at functionally distinct sites in the developing human urinary tract.
Understanding how urothelial cells are programmed and sustained, and how they regenerate will be
important for generating sub-populations from IPS cells and will be critical for developing new
strategies for treatment of patients with damaged bladders.

## Key facts

- **NIH application ID:** 9944541
- **Project number:** 5U01DK110803-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** CATHY Lee MENDELSOHN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $314,995
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944541

## Citation

> US National Institutes of Health, RePORTER application 9944541, GENERATING AN ATLAS OF THE DEVELOPING HUMAN URINARY OUTFLOW TRACT. (5U01DK110803-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944541. Licensed CC0.

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