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The Single Cell Landscape of Early Human Diabetic Nephropathy

Award Number: K08DK126847
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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The Single Cell Landscape of Early Human Diabetic Nephropathy - Project Summary/Abstract Diabetic kidney disease is the leading cause of end-stage renal disease and a major contributor to morbidity and mortality. We have successfully performed single nucleus RNA sequencing (snRNAseq) and single nucleus ATAC sequencing (snATACseq) on five healthy control and eight diabetic kidney samples to measure the cell-type-specific transcriptional and chromatin conformational profile of early human diabetic kidney disease. The differentially expressed transcripts in the diabetic proximal tubule showed upregulation of gluconeogenic genes and enrichment of pathways involved in corticosteroid signaling. This proposal aims to integrate snRNAseq and snATACseq to determine whether there are changes in chromatin accessibility in the enhancer and promoter regions of corticosteroid-sensitive genes that regulate gluconeogenesis. We will subsequently validate our in vivo findings with an in vitro model of diabetic injury and a diabetic mouse model. This proposal builds on the principal investigator’s previous research experience and clinical training. Currently, Dr. Parker Wilson is spending 25% of his time on the renal and molecular pathology clinical services with the remaining 75% allocated to basic research in Dr. Benjamin Humphreys’ laboratory. Dr. Wilson has an established mentoring relationship with Dr. Humphreys and has published his analysis of snRNAseq data from human diabetic kidney as a first author in PNAS. In addition, Dr. Wilson has a recently-accepted co-first author manuscript describing multimodal snRNAseq and snATACseq integration in the healthy adult kidney in Nature Communications. These findings provide the foundation for this application, which will focus on expanding Dr. Wilson’s scientific skills in single cell methods, bioinformatics analysis and models of diabetic kidney injury. The career development goals will be achieved through mentoring by Dr. Humphreys and an advisory committee with expertise in regulation of chromatin conformation, bioinformatics and diabetic nephropathy. Dr. Wilson will undertake didactic coursework in research ethics, scientific communication and grant writing, molecular biology and advanced computer programming to further his existing knowledgebase. The work will take place at Washington University, which has a strong history of mentoring successful physician-scientists. Completion of this career development award will build a solid foundation for Dr. Wilson as he pursues independence and R01-level funding.


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 = $167,940 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/19/2025	NON-COMPETING CONTINUATION	$167,940
														Subtotal = $167,940

Issue Date FY: 2025 ( Subtotal = $167,940 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/13/2024	NON-COMPETING CONTINUATION	$167,940
2025	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	1/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$18,340
2025	2022	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	1/23/2025	NEW	-$18,340
														Subtotal = $167,940

Issue Date FY: 2024 ( Subtotal = $167,940 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/12/2023	NON-COMPETING CONTINUATION	$167,940
														Subtotal = $167,940

Issue Date FY: 2023 ( Subtotal = $167,940 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	3/21/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$167,940
2023	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/21/2023	NEW	$0
														Subtotal = $167,940

Issue Date FY: 2022 ( Subtotal = $167,826 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/8/2021	NEW	$167,826
														Subtotal = $167,826

Grand Total All Awards = $839,586

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The Single Cell Landscape of Early Human Diabetic Nephropathy

Award Number: K08DK126847

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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