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Renal Circadian Clock Protein Regulation of Immune Activation

Award Number: K01DK135929
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Renal Circadian Clock Protein Regulation of Immune Activation - PROJECT SUMMARY/ABSTRACT: Kidney disease is a major contributor of death in the U.S. Chronic inflammation is common among individuals with chronic kidney disease. A diet high in salt or low in potassium is associated with increased inflammation and kidney injury. The renal handling of salt and potassium within distal segments of the nephron is linked to the circadian clock. Recently, distal segment cells have been linked to initiating tubulointerstitial inflammation. The research goal is to determine the mechanistic links between BMAL1 and activation of the immune system within distal segment cells of the kidney. Preliminary data identifies BMAL1 as a driver of inflammation in the kidney in response to a low K+/high salt diet, leading to kidney injury. Studies will use novel conditional knockout mouse models to reduce expression and re-express BMAL1 specifically in distal segment cells. The first aim will test the hypothesis that mice with decreased BMAL1 expression within distal segments display lower immune mediated kidney damage in response to low potassium with high salt diet. The second aim will test the hypothesis that BMAL1 within distal segments stimulates pro-inflammatory cytokine production in mice fed a low K+/high salt diet. To test these hypotheses, experiments to determine the localization and extent of renal injury, cytokine/chemokine production, immune cell recruitment and activation in response to a low K+/high salt diet are planned. These studies will establish a novel line of investigation aimed at understanding the link between the clock gene BMAL1 and activation of the immune system in the kidney. The long term goal of this work is to The training plan was carefully designed to build upon career development skills of the project leader focused around research advancement, education, and service to the scientific community. The experiments and career development will take place at the University of Florida, a top ten public research university that provides an outstanding environment for conducting biomedical research. Together, data from this award will provide a foundation for identifying new targets to treat renal inflammation/injury in order to improve the quality of life in individuals with kidney disease. The mentored training plan will provide the project leader with necessary technical and professional skills training needed to become an independent investigator.


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 = $137,752 )
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/30/2026	NON-COMPETING CONTINUATION	$137,752
														Subtotal = $137,752

Issue Date FY: 2025 ( Subtotal = $137,752 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/28/2025	NON-COMPETING CONTINUATION	$137,752
														Subtotal = $137,752

Issue Date FY: 2024 ( Subtotal = $139,252 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/29/2024	NEW	$139,252
														Subtotal = $139,252

Grand Total All Awards = $414,756

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Renal Circadian Clock Protein Regulation of Immune Activation

Award Number: K01DK135929

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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