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Cell Interactions in Development of the Mammalian Kidney

Award Number: R01DK054364
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/1998
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Cell Interactions in Development of the Mammalian Kidney - Project Summary / Abstract Approximately 1,000,000 Americans have end state renal disease and these numbers are increasing. Dialysis provides an essential but unsatisfactory palliative solution with high morbidity and high mortality. A kidney transplant can restore kidney function, but the number of transplants is insufficient for the patient population, and the numbers have not increased significantly over the last 20 years. Several groups have demonstrated the directed differentiation of kidney-like structures, kidney organoids, from mouse and human pluripotent stem cells. These advances highlight the need to generate an enhanced understanding of the critical processes underlying mammalian nephrogenic programs. Further, recent advances in our understanding of human kidney development from the McMahon group emphasize the importance of direct human studies. Consequently, we combine analysis across developing mouse and human kidney systems with human kidney organoids to examine key regulatory processes in the nephrogenic program. In Specific Aim 1, we will determine the epigenetic control mechanisms regulating normal mouse and human nephron progenitor states through extensive analysis of RNA-seq, ChIP-seq, ATAC-seq and HI-C datasets. The regulatory processes identified through these studies are interesting in their own right but serve also as a critical benchmark for in vitro efforts to generate normal nephron progenitor cells. In Specific Aim 2, we will determine the transcriptional mechanisms of Wnt/ß-catenin pathway mediated maintenance and commitment of nephron progenitor cells. Wnt signaling plays a central role in stem/progenitor regulation in a variety of organ systems. Recent advances in nephron progenitor culture and differentiation make the kidney an attractive model for unravelling the duality of Wnt pathway action on nephron progenitor cells. In Specific Aim 3, we will examine the role of canonical Wnt signaling in distal patterning of the developing nephron. In patterning the early nephron anlagen, several lines of evidence links Notch and Wnt signaling to proximal and distal fate-specification, respectively. We will examine the role of Wnt-signaling in distal development using human and optimized human pluripotent cell kidney organoid model system, genetically engineered to report on nephron patterning events. The anticipated research outcomes will identify critical regulatory mechanisms governing the maintenance, commitment and differentiation of stem/progenitor cell types of broad interest to researchers working across different organ systems. The studies will also enhance our understanding of human kidney development and educate effective therapeutic application of stem cell-derived kidney structures.


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: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	24	4/25/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $669,951 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	24	12/17/2021	NON-COMPETING CONTINUATION	$602,956
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	24	4/12/2022	NON-COMPETING CONTINUATION	$66,995
														Subtotal = $669,951

Issue Date FY: 2021 ( Subtotal = $669,951 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	12/29/2020	NON-COMPETING CONTINUATION	$602,956
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	23	2/2/2021	NON-COMPETING CONTINUATION	$66,995
														Subtotal = $669,951

Issue Date FY: 2020 ( Subtotal = $669,951 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	22	12/31/2019	NON-COMPETING CONTINUATION	$602,956
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	22	2/21/2020	NON-COMPETING CONTINUATION	$66,995
														Subtotal = $669,951

Issue Date FY: 2019 ( Subtotal = $687,177 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	21	3/28/2019	COMPETING CONTINUATION	$17,226
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	1/11/2019	COMPETING CONTINUATION	$669,951
														Subtotal = $687,177

Issue Date FY: 2007 ( Subtotal = $592,399 )
2007	2007	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	10	8/29/2007	NON-COMPETING CONTINUATION	$592,399
														Subtotal = $592,399

Issue Date FY: 2006 ( Subtotal = $592,723 )
2006	2006	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	9	8/17/2006	NON-COMPETING CONTINUATION	$592,723
														Subtotal = $592,723

Issue Date FY: 2005 ( Subtotal = $589,717 )
2005	2005	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	8	8/17/2005	NON-COMPETING CONTINUATION	$589,717
														Subtotal = $589,717

Issue Date FY: 2004 ( Subtotal = $572,950 )
2004	2004	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	7	8/23/2004	NON-COMPETING CONTINUATION	$572,950
														Subtotal = $572,950

Issue Date FY: 2003 ( Subtotal = $700,139 )
2003	2003	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	001	6	9/22/2003	SUPPLEMENT FOR EXPANSION	$113,890
2003	2003	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	6	9/19/2003	COMPETING CONTINUATION	$586,249
														Subtotal = $700,139

Issue Date FY: 2002 ( Subtotal = $412,970 )
2002	2002	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Kidney Diseases, Urology and Hematology Research	000	5	8/12/2002	NON-COMPETING CONTINUATION	$412,970
														Subtotal = $412,970

Issue Date FY: 2001 ( Subtotal = $401,214 )
2001	2001	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Kidney Diseases, Urology and Hematology Research	000	4	8/27/2001	NON-COMPETING CONTINUATION	$401,214
														Subtotal = $401,214

Issue Date FY: 2000 ( Subtotal = $389,803 )
2000	2000	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Kidney Diseases, Urology and Hematology Research	000	3	8/25/2000	NON-COMPETING CONTINUATION	$389,803
														Subtotal = $389,803

Issue Date FY: 1999 ( Subtotal = $378,723 )
1999	1999	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Kidney Diseases, Urology and Hematology Research	000	2	9/15/1999	NON-COMPETING CONTINUATION	$378,723
														Subtotal = $378,723

Issue Date FY: 1998 ( Subtotal = $377,228 )
1998	1998	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Kidney Diseases, Urology and Hematology Research	000	1	8/15/1998	NEW	$377,228
														Subtotal = $377,228

Grand Total All Awards = $7,704,896

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Cell Interactions in Development of the Mammalian Kidney

Award Number: R01DK054364

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/1998

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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