Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Defining the renal urothelium progenitor and its regulation during development and repair

Award Number: K01DK126991
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Defining the renal urothelium progenitor and its regulation during development and repair - PROJECT SUMMARY/ABSTRACT Congenital urinary tract obstruction (UTO) is a leading cause of chronic kidney disease and end stage renal disease in children. Current management strategies cannot prevent chronic kidney disease progression. Recently published data from my F32-funded postdoctoral studies identify renal urothelial remodeling as a protective adaptation to UTO. Both congenital and acquired UTO trigger the formation of Uroplakin (Upk) expressing urothelial cells (UC) that synthesize a bladder-like urothelial plaque. Depletion of urothelial plaque in mice with congenital UTO accelerates renal parenchymal loss, functional impairment, and death – attesting to key roles for Upk-UCs in preventing obstructive nephropathy. A greater understanding of renal urothelial development and repair may lead to therapies aimed at attenuating obstructive kidney disease. Fundamental knowledge gaps exist, however, in our understanding of the formation of Upk-UCs during development and UTO. I have recently demonstrated that Keratin 5 (K5)-expressing UCs differentiate into Upk-UCs during development and following UTO. This application takes direct aim at the hypothesis that K5-UCs are progenitors whose fate is governed by an intrinsic molecular program that varies over time and in response to injury. The anticipated outcome of this research is to establish molecular mechanisms that govern K5-UC progenitor activity, and to determine the contributions of K5-UC progenitors during development and following UTO. In Aim 1, I will investigate whether temporally restricted K5-UC progenitor activity is cell-intrinsic using organoid assays; examine the role of Notch signaling in the regulation of K5-UC fate; and define molecular programs that regulate urothelial development and repair. In Aim 2, I will investigate the significance of the K5-UCs by evaluating the impact of depletion and expansion of K5-UCs on urothelial development and repair during UTO. The studies proposed in this application will reveal the cellular and molecular basis of Upk-UC formation – with the hypothesis that K5-UCs form Upk-UCs in a Notch dependent manner. Successful completion of these aims will provide the foundation for the development of therapies that target K5-UCs for differentiation to attenuate obstructive kidney disease in patients with UTO. In fulfilling these Aims, I will develop critical skills in rare cell isolation, organoid development, signaling pathway analysis, bioinformatics, renal physiology and pathophysiology of obstructive nephropathy. Mastery of these skills, in combination with structured career development activities under the guidance of my mentors and research advisory team, will prepare me to successfully compete for R01 funding and launch my career as an independent scientist focused on developing therapies aimed at attenuating chronic kidney disease progression in children with UTO.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/8/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $145,295 )
2025	2025	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/18/2025	NON-COMPETING CONTINUATION	$145,295
														Subtotal = $145,295

Issue Date FY: 2024 ( Subtotal = $145,295 )
2024	2024	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/22/2024	NON-COMPETING CONTINUATION	$145,295
														Subtotal = $145,295

Issue Date FY: 2023 ( Subtotal = $145,295 )
2023	2023	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/25/2023	NON-COMPETING CONTINUATION	$145,295
														Subtotal = $145,295

Issue Date FY: 2022 ( Subtotal = $145,295 )
2022	2022	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/20/2022	NON-COMPETING CONTINUATION	$145,295
														Subtotal = $145,295

Issue Date FY: 2021 ( Subtotal = $146,795 )
2021	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/16/2021	NEW	$146,795
														Subtotal = $146,795

Grand Total All Awards = $727,975

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining the renal urothelium progenitor and its regulation during development and repair

Award Number: K01DK126991

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer