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Anti-inflammatory activity of hydrogels designed to capture extracellular inflammasomes

Award Number: R21AI178831
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Anti-inflammatory activity of hydrogels designed to capture extracellular inflammasomes - PROJECT SUMMARY/ABSTRACT Multiprotein complexes known as inflammasomes form in innate immune cells to trigger inflammation upon detection of pathogens or tissue damage. Abnormal inflammasome activation leads to chronic inflammation, which is the culprit of numerous life-threatening diseases such as cancer, diabetes, cardiovascular disorders, and the cytokine storm in SARS-CoV-2 infection. Inflammasome assembly is controlled by protein-protein interactions as it requires the self-association and oligomerization of multiple copies of three proteins: sensors to detect danger signals, a protease to activate inflammatory factors, and the adaptor protein ASC to connect sensor and protease. Inflammasome formation leads to plasma membrane rupture and concomitant cell death, thus resulting in the release of proinflammatory cytokines and inflammasome particles to the extracellular environment. These extracellular inflammasomes are internalized by nearby cells to perpetuate and amplify the inflammatory response. Removing or sequestering extracellular inflammasomes will likely inhibit or reduce inflammation. Therefore, extracellular inflammasomes are potential therapeutic targets. Our laboratory’s extensive experience on the function and structure of the adaptor ASC, and its interactions with other inflammasome proteins, has led us to create hydrogels designed to form specific protein-protein interactions with inflammasomes; thus, they have the potential to broadly inhibit inflammation by effectively capturing and removing extracellular inflammasomes. This project focuses on identifying the hydrogelation factors leading to optimum biding of inflammasome particles in cell-free systems (Aim 1); and determining the anti-inflammatory efficiency of the hydrogels in the presence of activated innate immune cells (Aim 2). Our experimental plan will combine cell biology and biochemical approaches, including live/dead cell imaging, flow cytometry, immunoblotting, enzyme-linked immunosorbent assays and fluorescence spectroscopy. Overall, we expect to develop a hydrogel technology of broad applicability to reduce inflammation in the absence of drug loading by targeting the inflammasome, which is implicated in many inflammatory diseases.


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 = -$4,513 )
2026	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	000	2	12/18/2025	NON-COMPETING CONTINUATION	-$4,513
														Subtotal = -$4,513

Issue Date FY: 2024 ( Subtotal = $183,186 )
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	000	2	6/6/2024	NON-COMPETING CONTINUATION	$183,186
														Subtotal = $183,186

Issue Date FY: 2023 ( Subtotal = $222,189 )
2023	2023	UNIVERSITY OF CALIFORNIA, MERCED FOUNDATION	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	000	1	6/16/2023	NEW	$222,189
														Subtotal = $222,189

Grand Total All Awards = $400,862

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Anti-inflammatory activity of hydrogels designed to capture extracellular inflammasomes

Award Number: R21AI178831

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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