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Genetic modifiers of Sickle Cell Kidney Disease

Award Number: K23HL157554
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Genetic modifiers of Sickle Cell Kidney Disease - Project Summary/Abstract This proposal presents a five-year research career development plan focused on prospectively studying the role of genetic polymorphisms in the development and progression of chronic kidney disease in sickle cell disease (SCD). The candidate, an assistant professor of pediatrics and attending nephrologist at the University of Tennessee Health Science Center at Memphis, has devised a research development plan that will provide mentorship, training and research experience to expedite her development into an independent clinician scientist in the field of genetic epidemiology. To achieve the candidate’s long-term goal of becoming an expert in genomic contributions to the development and progression of chronic kidney disease in individuals with sickle cell disease, the candidate and her mentorship team have devised the following development plan: 1) intensive, personal mentorship from an experienced team; 2) focused training on techniques in epidemiology and genomic analysis methods; and 3) an innovative research plan using a large and extensively phenotyped patient cohort with genomic data to study kidney disease manifestations. The candidate’s research development plan outlines a focused route to obtain the knowledge, skills and experience necessary to make a lasting impact in the field sickle cell disease-associated kidney disease. Compared with whites, African Americans have an increased risk for chronic kidney disease, resulting in irreversible end stage kidney disease and increased mortality. This racial disparity in kidney disease raised the possibility of genetic contributors and drove studies showing an association between the apolipoprotein L1 gene (APOL1) and development of CKD. Although APOL1 is a significant risk factor for the development of kidney disease in SCD, it does not fully account for the increased risk. This proposal will further address the role of APOL1 as well as other known genetic variants associated with CKD in SCD. The candidate will test two related hypotheses: a) -a3.7, HMOX1, BCL11A and APOL1 alleles act independently to modify the onset and progression of kidney disease in SCD and will have improved predictive power when considered together in a genetic risk profile (GRP) and analyzed longitudinally; and b) known genetic modifiers of CKD discovered in the general African American population also influence the development of kidney disease in SCD. This proposal will generate a multi-gene genetic risk profile to identify patients at increased risk for development and progression of kidney disease and will set the stage for future clinical studies investigating novel disease- modifying therapies.


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 = $166,559 )
2026	2026	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Blood Diseases and Resources Research	000	5	2/24/2026	NON-COMPETING CONTINUATION	$166,559
														Subtotal = $166,559

Issue Date FY: 2025 ( Subtotal = $168,179 )
2025	2025	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Blood Diseases and Resources Research	000	4	3/3/2025	NON-COMPETING CONTINUATION	$168,179
														Subtotal = $168,179

Issue Date FY: 2024 ( Subtotal = $168,557 )
2024	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Blood Diseases and Resources Research	000	3	2/2/2024	NON-COMPETING CONTINUATION	$168,557
														Subtotal = $168,557

Issue Date FY: 2023 ( Subtotal = $168,557 )
2023	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Blood Diseases and Resources Research	000	2	1/25/2023	NON-COMPETING CONTINUATION	$168,557
														Subtotal = $168,557

Issue Date FY: 2022 ( Subtotal = $176,846 )
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Blood Diseases and Resources Research	000	1	1/27/2022	NEW	$176,846
														Subtotal = $176,846

Grand Total All Awards = $848,698

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Genetic modifiers of Sickle Cell Kidney Disease

Award Number: K23HL157554

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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