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Molecular of ROMK Channel Function

Award Number: R01DK054231
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: 08/01/1998
PERIOD OF PERFORMANCE END DATE: 12/31/2027

Group Awards By:

View Award Description

Molecular of ROMK Channel Function - ROMK (Kir 1.1, the product of the KCNJ1 gene) channels in the distal nephron are exquisitely regulated to adjust renal potassium excretion and maintain potassium balance. Still, the underlying mechanisms have been a great mystery. Here we overcome this major conceptual roadblock, building on our recent discoveries of a mechanism we call the potassium switch. We identified two new elements of the switch pathway that regulate ROMK: structural remodeling of the connecting tubule (CNT), and a plasma potassium sensing signaling pathway in the CNT, composed of Kidney Specific (KS)-WNK1, WNK4, and ERK. To carry these breakthrough observations toward a completely new understanding of how potassium balance is achieved, we will use a stepwise multidisciplinary approach, combining molecular genetics, genomics, cellular biology, innovative imaging, state-of-the-art physiological phenotyping in novel mouse models, and mathematical modeling to: 1) Rigorously explore the physiology of newly developed inducible cell-specific ROMK knockout to determine if the regulated expression of ROMK in DCT2 and CNT controls potassium homeostasis, 2) Investigate the adaptive expansion of the CNT as a normal homeostatic mechanism that preserves potassium balance in the face of increased dietary potassium consumption. 3) Test if switch activation of the cell- fate determinants, Jagged 1-Notch 1/2, are required for proper remodeling of the CNT. 4) Explore a potassium-sensing signaling pathway that downregulates ROMK in potassium deficiency via KS-WNK1/WNK4/ERK5 phosphorylation of the clathrin adaptor, ARH, which targets ROMK for endocytosis. The pathway provides a molecular mechanism to explain how ROMK channels are regulated in hypokalemia and dietary potassium deficiency and pathologically misregulated in a human disease of familial hyperkalemia that is induced by gain-of-function mutations in the kidney-specific WNK1. The studies should provide novel insights into the molecular basis of renal K+ handling and K+ homeostasis in health and disease while illuminating novel drug targets for the treatment of common hyperkalemic disorders.


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 = $688,972 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	1/6/2026	NON-COMPETING CONTINUATION	$688,972
														Subtotal = $688,972

Issue Date FY: 2025 ( Subtotal = $622,620 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	22	1/1/2025	NON-COMPETING CONTINUATION	$622,620
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	12/31/2024	COMPETING CONTINUATION	$0
														Subtotal = $622,620

Issue Date FY: 2024 ( Subtotal = $724,020 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	1/15/2024	COMPETING CONTINUATION	$723,720
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	21	2/28/2024	COMPETING CONTINUATION	$300
														Subtotal = $724,020

Issue Date FY: 2022 ( Subtotal = -$296 )
2022	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	8/30/2022	NON-COMPETING CONTINUATION	-$296
														Subtotal = -$296

Issue Date FY: 2020 ( Subtotal = $506,175 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	20	4/1/2020	NON-COMPETING CONTINUATION	$506,175
2020	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	18	4/13/2020	NON-COMPETING CONTINUATION	-$30,077
2020	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	19	2/6/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$195,423
2020	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	19	4/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$30,077
2020	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	18	2/5/2020	NON-COMPETING CONTINUATION	-$1
2020	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	1/30/2020	NON-COMPETING CONTINUATION	-$195,422
														Subtotal = $506,175

Issue Date FY: 2019 ( Subtotal = $482,370 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	3/19/2019	NON-COMPETING CONTINUATION	$482,370
														Subtotal = $482,370

Issue Date FY: 2018 ( Subtotal = $482,370 )
2018	2018	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	4/30/2018	NON-COMPETING CONTINUATION	$482,370
														Subtotal = $482,370

Issue Date FY: 2017 ( Subtotal = $454,299 )
2017	2017	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	16	6/7/2017	COMPETING CONTINUATION	$495,647
2017	2014	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	11/2/2016	NON-COMPETING CONTINUATION	-$41,348
														Subtotal = $454,299

Issue Date FY: 2014 ( Subtotal = $308,138 )
2014	2014	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	5/21/2014	NON-COMPETING CONTINUATION	$308,138
														Subtotal = $308,138

Issue Date FY: 2013 ( Subtotal = $343,273 )
2013	2013	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	5/24/2013	NON-COMPETING CONTINUATION	$343,273
														Subtotal = $343,273

Issue Date FY: 2012 ( Subtotal = $355,723 )
2012	2012	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	7/24/2012	SUPPLEMENT FOR EXPANSION	$47,585
2012	2012	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	5/23/2012	NON-COMPETING CONTINUATION	$308,138
														Subtotal = $355,723

Issue Date FY: 2011 ( Subtotal = $308,138 )
2011	2011	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	6/7/2011	NON-COMPETING CONTINUATION	$308,138
														Subtotal = $308,138

Issue Date FY: 2010 ( Subtotal = $375,000 )
2010	2010	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	5/28/2010	COMPETING CONTINUATION	$375,000
2010	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	6/7/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $375,000

Issue Date FY: 2009 ( Subtotal = $212,504 )
2009	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	2/26/2009	NON-COMPETING CONTINUATION	$21,251
2009	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	11/19/2008	NON-COMPETING CONTINUATION	$191,253
														Subtotal = $212,504

Issue Date FY: 2008 ( Subtotal = $212,504 )
2008	2008	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	000	9	12/3/2007	NON-COMPETING CONTINUATION	$212,504
														Subtotal = $212,504

Issue Date FY: 2007 ( Subtotal = $216,840 )
2007	2007	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	000	8	11/23/2006	NON-COMPETING CONTINUATION	$216,840
														Subtotal = $216,840

Issue Date FY: 2006 ( Subtotal = $223,316 )
2006	2006	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	000	7	12/5/2005	NON-COMPETING CONTINUATION	$223,316
														Subtotal = $223,316

Issue Date FY: 2005 ( Subtotal = $228,690 )
2005	2005	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	000	6	1/6/2005	COMPETING CONTINUATION	$228,690
														Subtotal = $228,690

Issue Date FY: 2002 ( Subtotal = $415,115 )
2002	2002	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	001	4	5/24/2002	SUPPLEMENT FOR EXPANSION	$51,674
2002	2002	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Kidney Diseases, Urology and Hematology Research	000	5	6/21/2002	NON-COMPETING CONTINUATION	$363,441
														Subtotal = $415,115

Grand Total All Awards = $8,087,917

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Molecular of ROMK Channel Function

Award Number: R01DK054231

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: 08/01/1998

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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