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Role of bFGF low affinity receptors in childhood HIVAN

Award Number: R01DK049419
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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Role of bFGF low affinity receptors in childhood HIVAN - PROJECT SUMMARY/ABSTRACT Most of the 2.5 million children and adolescents living with HIV-1 (CALWH) worldwide reside in Sub-Saharan Africa. Those who carry two copies of the APOL1 risk alleles (RA) are at higher risk of developing HIV-chronic kidney diseases (HIV-CKD) if they are not treated continuously with modern anti-retroviral therapy (ART) throughout childhood. During the last grant cycle, we followed the outcome of ~ 200 CALWH in the Washington DC area for an average period of 5 years, and found that many developed HIV-CKD despite ART. We also found that children with high plasma and urine levels of the heparin binding cytokine Fibroblast Growth Factor-2 (FGF- 2), were at further risk of developing HIV-CKD, and that FGF-2 increased the renal recruitment and attachment of HIV+ cells in mice. Thus, we hypothesize that FGF-2 release into the circulation accelerates the progression of childhood HIV-CKD, acting in synergy with the APOL1-RA and other HIV proteins, by facilitating the renal recruitment of HIV-infected cells, as well as the infection and/or injury of renal cells despite ART. We further hypothesize that FGF-2 precipitates the detachment of viable podocytes and tubular epithelial cells (REc), and that the phenotype and transcriptome profiles of these cells can be used to distinguish CALWH undergoing HIVAN and/or other progressive HIV-CKD, and to follow their outcome in a non-invasive manner. This hypothesis will be tested in three aims. In aim 1, we will define how FGF-2 and APOL1-RA interact to precipitate HIV-CKDs in CALWH on ART, and define the clinical value of single cell urinary transcriptome profiles to distinguish CALWH undergoing HIVAN and/or other progressive HIV-CKD. In aim 2, we will determine how FGF-2 and APOL1-RA interact to modulate the infection, injury, and/or survival of HIV-infected cells cultured from children with HIV- CKD. In aim 3, we will use two new mouse models of childhood HIV-CKD, to determine how FGF-2 interacts with APOL1-RA and HIV-Nef to precipitate the detachment of podocytes/REc and accelerate the progression of HIV-CKD. In addition, we will identify the most relevant signaling pathways involved in these processes, and define how drugs that block the selected pathways affect the progression of HIV-CKD in young mice.


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 = $500,838 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	22	10/1/2023	NON-COMPETING CONTINUATION	-$37,804
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	22	8/23/2024	NON-COMPETING CONTINUATION	$538,642
														Subtotal = $500,838

Issue Date FY: 2023 ( Subtotal = $561,085 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	21	6/28/2023	NON-COMPETING CONTINUATION	$561,085
2023	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	20	6/23/2023	COMPETING CONTINUATION	$279,461
2023	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	6/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$279,461
														Subtotal = $561,085

Issue Date FY: 2022 ( Subtotal = $576,460 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	20	7/27/2022	COMPETING CONTINUATION	$0
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	4/25/2022	COMPETING CONTINUATION	$576,460
														Subtotal = $576,460

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	8/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = -$4,197 )
2020	2018	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	2/18/2020	NON-COMPETING CONTINUATION	-$214,048
2020	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	19	2/27/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$516,217
2020	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	19	2/19/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$209,851
2020	2018	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	18	2/27/2020	NON-COMPETING CONTINUATION	-$179,702
2020	2017	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	17	2/27/2020	NON-COMPETING CONTINUATION	-$336,515
														Subtotal = -$4,197

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	9/11/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $393,750 )
2018	2018	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	7/9/2018	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2017 ( Subtotal = $393,750 )
2017	2017	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	8/4/2017	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2016 ( Subtotal = $397,236 )
2016	2016	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	16	6/22/2016	NON-COMPETING CONTINUATION	$393,750
2016	2015	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	3/29/2016	COMPETING CONTINUATION	$3,486
														Subtotal = $397,236

Issue Date FY: 2015 ( Subtotal = $387,000 )
2015	2015	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	7/15/2015	COMPETING CONTINUATION	$387,000
														Subtotal = $387,000

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2012	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	9/1/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $284,061 )
2012	2012	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	8/21/2012	NON-COMPETING CONTINUATION	$284,061
														Subtotal = $284,061

Issue Date FY: 2011 ( Subtotal = $364,661 )
2011	2011	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	12/24/2010	SUPPLEMENT FOR EXPANSION	$40,503
2011	2011	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	8/9/2011	NON-COMPETING CONTINUATION	$324,158
														Subtotal = $364,661

Issue Date FY: 2010 ( Subtotal = $258,000 )
2010	2010	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	12	8/24/2010	COMPETING CONTINUATION	$258,000
2010	2008	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Kidney Diseases, Urology and Hematology Research	001	11	8/20/2010	NON-COMPETING CONTINUATION	$0
2010	2008	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Kidney Diseases, Urology and Hematology Research	000	11	3/10/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $258,000

Issue Date FY: 2008 ( Subtotal = $441,208 )
2008	2008	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Kidney Diseases, Urology and Hematology Research	000	11	2/20/2008	NON-COMPETING CONTINUATION	$296,531
2008	2008	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	2/25/2008	SUPPLEMENT FOR EXPANSION	$144,677
														Subtotal = $441,208

Issue Date FY: 2007 ( Subtotal = $443,683 )
2007	2007	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Kidney Diseases, Urology and Hematology Research	000	10	3/2/2007	NON-COMPETING CONTINUATION	$241,779
2007	2007	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	10	3/6/2007	SUPPLEMENT FOR EXPANSION	$141,100
2007	2007	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	3/5/2007	SUPPLEMENT FOR EXPANSION	$60,804
														Subtotal = $443,683

Issue Date FY: 2006 ( Subtotal = $249,000 )
2006	2006	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVENUE, NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Kidney Diseases, Urology and Hematology Research	000	9	3/20/2006	COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2002 ( Subtotal = $294,661 ) (Continued on the next page)
Grand Total All Awards = $6,627,336

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Role of bFGF low affinity receptors in childhood HIVAN

Award Number: R01DK049419

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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