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Targeting kidney resident macrophage niche filling to slow cystic kidney disease

Award Number: F31DK137568
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 12/18/2025

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Targeting kidney resident macrophage niche filling to slow cystic kidney disease - PROJECT SUMMARY/ABSTRACT Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease in the world. It is characterized by large fluid-filled cysts that disrupt kidney function, eventually leading to end stage kidney disease. Previous literature indicates that kidney resident macrophages (KRM) are cyst-associated in human clinical samples and are also found in cystic regions of ADPKD mouse models. KRM accelerate ADPKD as depletion of KRM reduces cystic index and disease progression in mouse models of the disease. Together, these data suggest that targeting KRM may have a clinical impact in patients. Unfortunately, it is currently not feasible to give patients macrophage depleting agents for long periods as these compounds lack specificity, depleting macrophage populations in multiple tissues. This is an important point as macrophages perform critical functions as part of an organism’s innate immune defense. Additionally, ADPKD progresses slowly and patients experience gradual cyst growth and loss of kidney function over several decades of life, thereby requiring long- term intervention. These data highlight that alternative approaches for long-term, kidney-specific resident macrophage depletion are desperately needed. In this application, I propose to study niche filling as a means to achieve long term, kidney specific resident macrophage depletion. This will be achieved by determining the mechanism of KRM niche filling after temporary depletion and through identification of factors, such as Cx3cr1, that we propose are critical for KRM niche filling. The central hypothesis of this proposal is that following temporary depletion, the KRM niche is repopulated via the recruitment and differentiation of bone marrow- derived Ly6chi monocytes and that this process requires Cx3cr1. In Aim 1, I will map out the kinetics and mechanism of KRM niche after temporary depletion in a mouse model of ADPKD. In Aim 2, I will test if loss of Cx3cr1 in monocytes is able to delay KRM niche filling and the progression of cystic disease. My long-term goal is to understand the mechanism of KRM niche filling and translationally apply KRM-centric findings to clinical cases of ADPKD.


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 = -$10,556 )
2026	2025	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/5/2026	NON-COMPETING CONTINUATION	-$10,556
														Subtotal = -$10,556

Issue Date FY: 2025 ( Subtotal = $38,003 )
2025	2025	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/10/2025	NON-COMPETING CONTINUATION	$564
2025	2025	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/10/2025	NON-COMPETING CONTINUATION	$37,439
														Subtotal = $38,003

Issue Date FY: 2024 ( Subtotal = $37,439 )
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	5/3/2024	NEW	$1,280
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/27/2024	NEW	$36,159
														Subtotal = $37,439

Grand Total All Awards = $64,886

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Targeting kidney resident macrophage niche filling to slow cystic kidney disease

Award Number: F31DK137568

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 12/18/2025

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