Thursday, November 21, 2024 11/21/2024

Studies on the structure of basement membranes

Award Number: R01DK018381
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

The collagen IVα345 (Col-IVα345) scaffold, the major constituent of the glomerular basement membrane (GBM), is a critical component of the kidney glomerular filtration barrier. In chronic kidney disease, affecting hundreds of millions of people worldwide, over two thousand genetic variants occur in the COL4A3, COL4A4, and COL4A5 genes that encode the α3, α4, and α5 chains of the Col-IVα345 scaffold. The chains are the autoantigens in Goodpasture’s (GP) autoimmune disease, mutated in Alport syndrome, and dysfunctional in diabetic nephropathy (DN). The rationale development of therapy hinges on gaining new understandings of pathogenic mechanisms. GP disease, a renal pulmonary disorder, continues to serve as the vanguard for unlocking these medical mysteries. Among our discoveries are: a) the crystal structure of the NC1 hexamer of the α345 collagen IV scaffold, b) discovery of the primordial chloride pressure and its constraint against neoepitope formation in Goodpasture’s disease3, c) discovery of functionality of the α345 NC1 hexamer in the assembly of the GBM as an ultrafilter of proteins, d) development of the collagen triple-helix mapping tool, e) capacity of NC1 domain to home in the assembly of basement membranes, and f) detrimental effect of high glucose on the BM modifying enzymes. These published discoveries, together with substantial amount of unpublished pilot data, provide the framework for four specific aims. Our overarching hypothesis is: Col-IVα345 tethers macromolecules forming supramolecular complexes, perturbation of which, in genetic and acquired disorders, cause glomerulopathies. The achievement of the aims will yield new insights into the etiology of GP, the structure and assembly of collagen IV scaffolds and binding partners, and the molecular mechanisms of underlying DN. This knowledge is of fundamental importance for the rationale design of therapies that target the primary cause disease.


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 = $758,503 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	53	8/11/2024	COMPETING CONTINUATION	$758,503
2024	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	52	8/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $758,503

Issue Date FY: 2023 ( Subtotal = $746,708 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	52	4/18/2023	NON-COMPETING CONTINUATION	$746,708
														Subtotal = $746,708

Issue Date FY: 2022 ( Subtotal = $747,082 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	51	4/29/2022	NON-COMPETING CONTINUATION	$747,082
														Subtotal = $747,082

Issue Date FY: 2021 ( Subtotal = $747,830 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	50	3/30/2021	NON-COMPETING CONTINUATION	$747,830
														Subtotal = $747,830

Issue Date FY: 2020 ( Subtotal = $812,466 )
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	006	49	8/25/2020	COMPETING CONTINUATION	$0
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	49	3/5/2020	COMPETING CONTINUATION	$746,708
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	007	49	9/3/2020	SUPPLEMENT FOR EXPANSION	$65,758
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	49	8/4/2020	COMPETING CONTINUATION	$420,180
2020	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	48	2/21/2020	NON-COMPETING CONTINUATION	$0
2020	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	48	8/4/2020	SUPPLEMENT FOR EXPANSION	-$46,847
2020	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	48	2/21/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	48	8/4/2020	NON-COMPETING CONTINUATION	-$373,333
														Subtotal = $812,466

Issue Date FY: 2019 ( Subtotal = $741,902 )
2019	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	48	8/8/2019	NON-COMPETING CONTINUATION	$695,055
2019	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	48	8/28/2019	SUPPLEMENT FOR EXPANSION	$46,847
														Subtotal = $741,902

Issue Date FY: 2018 ( Subtotal = $878,858 )
2018	2018	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	47	6/7/2018	NON-COMPETING CONTINUATION	$878,858
														Subtotal = $878,858

Issue Date FY: 2017 ( Subtotal = $878,858 )
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	46	8/10/2017	NON-COMPETING CONTINUATION	$730,605
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	46	9/11/2017	SUPPLEMENT FOR EXPANSION	$148,253
														Subtotal = $878,858

Issue Date FY: 2016 ( Subtotal = $709,744 )
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	45	9/16/2016	NON-COMPETING CONTINUATION	-$709,275
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	006	45	9/17/2016	NON-COMPETING CONTINUATION	$709,275
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	45	9/12/2016	NON-COMPETING CONTINUATION	$704,786
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	45	9/15/2016	NON-COMPETING CONTINUATION	$4,489
2016	2015	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	44	7/12/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$74,069
2016	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	43	7/13/2016	COMPETING CONTINUATION	-$26,721
2016	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	43	5/24/2016	COMPETING CONTINUATION	-$46,879
														Subtotal = $709,744

Issue Date FY: 2015 ( Subtotal = $704,786 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	43	9/15/2015	COMPETING CONTINUATION	$704,786
														Subtotal = $704,786

Issue Date FY: 2014 ( Subtotal = $567,177 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	42	8/7/2014	NON-COMPETING CONTINUATION	$567,177
														Subtotal = $567,177

Issue Date FY: 2013 ( Subtotal = $563,742 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	41	8/8/2013	NON-COMPETING CONTINUATION	$563,742
														Subtotal = $563,742

Issue Date FY: 2012 ( Subtotal = $598,867 )
2012	2012	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	40	8/16/2012	NON-COMPETING CONTINUATION	$598,867
														Subtotal = $598,867

Issue Date FY: 2011 ( Subtotal = $731,157 )
2011	2011	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	39	8/26/2011	NON-COMPETING CONTINUATION	$666,390
2011	2011	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	38	3/4/2011	SUPPLEMENT FOR EXPANSION	$64,767
														Subtotal = $731,157

Issue Date FY: 2010 ( Subtotal = $737,042 )
2010	2010	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	38	9/7/2010	COMPETING CONTINUATION	$737,042
														Subtotal = $737,042

Issue Date FY: 2000 ( Subtotal = $375,000 )
2000	2000	UNIVERSITY OF KANSAS, MEDICAL CENTER	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	8/14/2000	COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 1999 ( Subtotal = $360,759 ) (Continued on the next page)
Grand Total All Awards = $12,010,098

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Studies on the structure of basement membranes

Award Number: R01DK018381

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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