Friday, October 3, 2025 10/3/2025

SLE-AWARE: SLE-- A Window into APOL1 Regulation andExpression

Award Number: K23AI163359
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/20/2021
PERIOD OF PERFORMANCE END DATE: 01/15/2024

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SLE-AWARE: SLE-- A Window into APOL1 Regulation andExpression - PROJECT SUMMARY/ABSTRACT Background: Approximately 13% of African Americans (AA), who suffer disproportionately from kidney and cardiovascular disease, carry two copies of the Apolipoprotein L1 (APOL1) gene risk variants (RV). These RVs contribute to renal and cardiovascular mortality, yet no therapies address gene mechanism. In cell culture and animal models, inflammatory cytokines increase APOL1 expression and worsen APOL1 high-risk genotype (HRG) related injury. The degree to which immune activation and resultant increased APOL1 expression synergizes with APOL1 genotype to precipitate human disease, such as lupus nephritis, is not understood. We will test the overarching hypothesis that APOL1 HRG SLE patients experience worsened disease features both due to SLE inflammatory mediators which induce gene expression and to protein coding changes carried on the variant allele. Importantly, an unprecedented number of biologic therapies are available to pharmacologically modulate immune pathways. Therefore understanding the relative contribution of specific immune pathways to APOL1 HRG associated disease may offer new treatment opportunities in this sensitive population. Preliminary Data: In our unique, AA SLE cohort and Ghanaian replication cohort, our group reproducibly identified APOL1 HRG associated traits including hypertension, renal dysfunction, and early atherosclerosis. Both in SLE monocytes and primary monocyte cell cultures, we identified SLE-relevant immune stimuli that induce APOL1 expression. We showed that HRG monocytes in response to high APOL1 expression exhibit mitochondrial dysfunction. These findings have clinical implications as they support a strategy aimed at reducing immune activation to mitigate APOL1 expression and resultant HRG associated disease features. Methods: To understand APOL1 immune regulation, we will analyze SLE patient monocyte transcriptional profiles by RNA-seq to assess immune pathway activation. APOL1 genotype, APOL1 transcriptional expression, and immune pathway scores will be tested for association with clinical outcomes, independently and in interaction models. We will determine whether increased APOL1 expression synergizes with risk genotype, and which immune system pathways reflected in the RNA-seq data are associated with APOL1 expression. We will validate the human transcriptional analysis using in-vitro monocyte cell culture models. Objectives and Career Development: This proposal leverages unique clinical and laboratory resources, and highly collaborative environment between experts in statistical genetics, functional genomics, immunology, cardiology, and rheumatology. It will lay the groundwork to propose future larger-scale studies designed to target specific immune pathways in APOL1 HRG patients. Furthermore, it will allow the PI to become an expert in the functional genomics of autoimmune disease and related kidney and vascular comorbidities, genetic modeling in complex clinical traits, and innovative laboratory and computational techniques. Thus, this will provide a framework for the PI’s independent translational career.


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: 2025 ( Subtotal = $428,131 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	6	8/8/2025	NON-COMPETING CONTINUATION	$197,640
2025	2023	THE HOSPITAL FOR SPECIAL SURGERY FUND, INC.	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	001	4	9/8/2025	NON-COMPETING CONTINUATION	$230,491
														Subtotal = $428,131

Issue Date FY: 2024 ( Subtotal = $197,640 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	5	7/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$197,640
2024	2023	THE HOSPITAL FOR SPECIAL SURGERY FUND, INC.	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	000	4	7/30/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $197,640

Issue Date FY: 2023 ( Subtotal = $197,640 )
2023	2023	HOSPITAL FOR SPECIAL SURGERY FUND, INC., THE	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	001	4	8/16/2023	NON-COMPETING CONTINUATION	$197,640
2023	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	5/15/2023	NEW	$0
														Subtotal = $197,640

Issue Date FY: 2022 ( Subtotal = $197,640 )
2022	2022	HOSPITAL FOR SPECIAL SURGERY FUND, INC., THE	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	002	3	8/18/2022	NON-COMPETING CONTINUATION	$197,640
2022	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	6/27/2022	NEW	-$147,305
2022	2021	HOSPITAL FOR SPECIAL SURGERY FUND, INC., THE	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	004	2	8/26/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$10,094
2022	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	005	1	8/31/2022	NEW	$0
2022	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	003	1	8/26/2022	NEW	$10,094
2022	2021	HOSPITAL FOR SPECIAL SURGERY FUND, INC., THE	535 E 70TH ST	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	001	2	6/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$147,305
														Subtotal = $197,640

Issue Date FY: 2021 ( Subtotal = $199,260 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	9/20/2021	NEW	$199,260
														Subtotal = $199,260

Grand Total All Awards = $1,220,311

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SLE-AWARE: SLE-- A Window into APOL1 Regulation andExpression

Award Number: K23AI163359

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/20/2021

PERIOD OF PERFORMANCE END DATE: 01/15/2024

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