# Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Injury

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $1,199,999

## Abstract

OVERALL: PROJECT SUMMARY/ABSTRACT
The Columbia University George M. O’Brien Urology Cooperative Research Center is made up of Columbia’s
leading Urologists, Microbiologists, Geneticists, Developmental and Cell Biologists dedicated to solving the
central problems of Benign Urology. Our focus builds on the work conducted in prior cycles and proposes to
identify solutions to clinical diseases at the juncture between clinical urology, epithelial biology and microbiology.
Our faculty include the leading clinical and scientific minds at Columbia, including Chairs and Professors of
Urology, Nephrology, Pathology & Cell Biology, Genetics & Development and Medicine. Together our faculty
provide the expertise to identify the root causes of urologic disability in three scientific groups. Dr Gharavi has
identified major risk loci for vesiculoureteral reflux and is now correlating developmental phenotypes with both
changes in the urinary microbiome and lower urinary tract symptoms. Dr Gharavi’s tools include large datasets
such as the Lower Urinary Tract Symptoms Research Network (LURN), the UK Biobank and the eMERGE
consortium. This effort establishes the field of personalized genomics in benign urology. Dr Mendelsohn
evaluates signaling pathways downstream of Pparg, a nuclear receptor that turns out to be a major regulator of
cell type specific differentiation in the urothelium, as well as the inflammatory response to injury and infection.
The work identifies an off-the-shelf drug that can be a potential treatment for urothelial repair. Dr Barasch focuses
on epithelial metabolism identifying a central mechanism of defense against UTI called “nutritional immunity”. He
discovered NGAL a protein that blocks iron capture by bacteria, and now has identified a highly active pathway
of heme metabolism that produce CO gas. His tools include novel methods of RNA isolation from small amounts
of cells, novel probes and chelators of CO, of heme and iron and reporter bacteria and mice. Dr Uhlemann
focuses on the evolutionary basis of drug-resistant microorganisms deciphering their molecular mechanisms of
virulence. The Microbial Genomics Biomedical Core not only directs all microbiological studies in the O’Brien but
also serves as a national resource for microbiome and metagenomic analyses and as a biorepository for drug-
resistant UTI isolates. The excitement of our group is encapsulated in the interactions of each component of
research from gene discovery to therapeutic applications including both human and mouse models. In this new
cycle, we will continue to contribute to urological sciences by generating new genomics datasets (to be shared
on dbGAP and GEO), gene lists, animal models (deposited at JAX), bacterial gene editing plasmids and reagents
that can be shared with the urology community. We will continue to collaborate with urology experts in Wisconsin,
Missouri, Maryland. We will fund new Opportunity Pool recipients, building on the roster of 6 new investigat...

## Key facts

- **NIH application ID:** 10487483
- **Project number:** 5U54DK104309-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JONATHAN M. BARASCH
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,199,999
- **Award type:** 5
- **Project period:** 2014-09-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487483

## Citation

> US National Institutes of Health, RePORTER application 10487483, Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Injury (5U54DK104309-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10487483. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*