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Covid 19 cytokine storm

Award Number: R01DK129522
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Covid 19 cytokine storm - Abstract The COVID 19 pandemic has been associated with the development of proteinuria in up to 40% of hospitalized patients. This cardinal manifestation of kidney disease is most likely related to effects of the extensive cytokine storm in these patients on glomeruli, the filtering units of the kidney. Using five years of experience with studying cytokine storms related to Common Cold induced relapse of some forms of human kidney disease, we developed four novel “cytokine cocktail” models of the COVID 19 cytokine storm. These cytokine cocktails contain components of the Innate and Adaptive immune response in a specific additive sequence and induce acute albuminuria in mice. Also included in the cocktails is soluble Angiotensin Converting Enzyme 2 (sACE2), a circulating form of the receptor for COVID 19 in humans. The presence of heightened kidney disease in mice that are hypomorphs for the podocyte expressed transcriptional factor Zhx2 may provide a partial genetic basis for greater severity of disease in select populations. Using cytokine depletion and cytokine receptor blockage, we noted that it is possible to developed treatment strategies to treat COVID related kidney disease. In Specific Aim 1, we will conduct mechanistic studies in the podocyte related to the effect of cytokine cocktail on the Interleukin 4 receptor, Interleukin 13 receptor, Tumor Necrosis Factor α receptor, and transmembrane ACE2. In vivo studies using knockout mice and in vitro studies using cultured podocytes will be conducted. In Specific Aim 2, we will investigate mechanisms involved in the pathogenesis of COVID 19 related glomerular disease, especially collapsing glomerulopathy. Mice deficient in glomerular endothelial Integrin β5 expression, podocyte Zhx2 expression, or both will be used. Combination of Integrin β5 expression deficient mice with those also deficient in podocyte cytokine receptors and Tumor Necrosis Factor α receptor will be used to study paracrine and autocrine feedback loops. In Specific Aim 3, we will conduct systematic current cytokine depletion and receptor blockage strategies, and also use them in combination to develop a novel therapeutic paradigm for the treatment of COVID 19 related glomerular disease. It is likely that these depletion strategies will benefit other end organ damage caused by the COVID 19 cytokine storm.


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 = -$13,882 )
2026	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/19/2026	NON-COMPETING CONTINUATION	-$13,882
														Subtotal = -$13,882

Issue Date FY: 2024 ( Subtotal = $556,406 )
2024	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/18/2024	NON-COMPETING CONTINUATION	$556,406
														Subtotal = $556,406

Issue Date FY: 2023 ( Subtotal = $626,464 )
2023	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/1/2023	NON-COMPETING CONTINUATION	$626,464
														Subtotal = $626,464

Issue Date FY: 2022 ( Subtotal = $626,089 )
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/2/2022	NON-COMPETING CONTINUATION	$626,089
2022	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/2/2021	NEW	$0
														Subtotal = $626,089

Issue Date FY: 2021 ( Subtotal = $562,646 )
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/9/2021	NEW	$562,646
														Subtotal = $562,646

Grand Total All Awards = $2,357,723

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Covid 19 cytokine storm

Award Number: R01DK129522

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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