# Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Urinary Tract Infection

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $1,200,000

## Abstract

OVERALL: PROJECT SUMMARY/ABSTRACT
The Columbia University George M. O’Brien Urology Cooperative Research Center brings together an
experienced group of investigators with a long track record of productive collaboration to address the causes of
the most common benign genitourinary disease, urinary tract infection (UTI). UTIs are prevalent in the United
States with 13.3% of women, 2.3% of men and 3.4% of children requiring medical intervention due to E. coli
infection of the urethra, bladder, ureter, and kidney. Since 2014, the Columbia O’Brien Research Center has
investigated the origins of common developmental defects of the pediatric genitourinary system that cause
urinary tract obstruction in human and mouse models. For the proposed renewal application, the Center will build
upon these efforts and employ a multidisciplinary approach to address the genetic, cellular, and metabolic events
that are important in maintaining urothelial homeostasis and that contribute to the body’s response to UTI. The
Center consists of three Research Projects, a new Microbial Genomics Biomedical Core (MGBC), and an
Administrative Core. Project 1 will determine the influence of the host genome and the urinary microbiome in
UTI, as well as genitourinary structural defects in humans. Project 2 will use mouse models to investigate how
the transcriptional regulation of urothelial differentiation differs between normal homeostasis and repair during
UTI. Project 3 will elucidate how a novel metabolic pathway, the “heme machine”, regulates UTI in the bladder.
The scientific aims for each of these projects are highly interconnected, and will require a dynamic exchange of
knowledge, seamless data sharing, and multidisciplinary, collaborative efforts to achieve success. To achieve
these aims, the three projects will be supported by the MGBC that will provide high-quality services for
biobanking, extended bacterial culture, microbial genomics (microbiome analyses, comparative genomics,
RNASeq), microbial genetics, and consultation for study design. Additionally, the Administrative Core will provide
the supporting framework for the Projects and MGBC in addition to integrating and overseeing all of the Center’s
activities including the Educational Enrichment Program and the Opportunity Pool Program. Over the past five
years, the Center has placed a major emphasis on educating the next generation of clinician-scientists in urologic
research, with annual retreats, seminar series, a summer student training program, and minority outreach
programs. We have also successfully used the Opportunity Pool mechanism to interact with other NIDDK-funded
centers and to attract new investigators to study important disorders in benign urology. Building on our
experience from the last five years and leveraging the infrastructure of Columbia’s top-tier biomedical research
institution, this proposed renewal will continue to foster multi- and interdisciplinary collaborations between basic,
translati...

## Key facts

- **NIH application ID:** 10022300
- **Project number:** 5U54DK104309-07
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JONATHAN M. BARASCH
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,200,000
- **Award type:** 5
- **Project period:** 2014-09-24 → 2021-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022300

## Citation

> US National Institutes of Health, RePORTER application 10022300, Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Urinary Tract Infection (5U54DK104309-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022300. Licensed CC0.

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