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Integrating Real-Time Multi-System Cytokine Signaling in Chronic Disease

Award Number: R35GM142833
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Integrating Real-Time Multi-System Cytokine Signaling in Chronic Disease - Project Summary/Abstract Over the next five years, my laboratory aims to study time-resolved systemic inflammation across multiple chronic diseases. Though pro-inflammatory cytokine signaling is common amongst chronic diseases, it is unclear what cytokines are active at various timepoints throughout disease initiation and progression. It is also unclear what cytokines are functional in the inflection from acute to chronic-phase inflammatory signaling. Current methods of research evaluation are not amenable to rapid kinetics (enzymatic immunoassays) or quantitative multiplexing (molecular imaging techniques). We plan to use a fluorescent carbon nanosensor-based platform I have previously developed, modified to rapidly detect pro-inflammatory cytokines in a multiplexed manner. The multiplexed cytokine nanosensor will be encapsulated within an injectable hydrogel matrix for minimally-invasive implantation and rapid measurement. We will use this sensor platform to create a cytokine signal detection network for both circulating and in situ cytokine signals in rodent models of chronic diseases. The nanosensor network will initially be validated in healthy mice using exogenous cytokine injection. We will ensure the sensor detects multiple cytokines simultaneously, at disease-relevant concentrations, is functional for months, and exhibits no specificity issues. The encapsulating hydrogel matrix will be designed to allow passage of proteins but retention of the sensor based on size, and will undergo minimal biofouling. Following technology validation, we will use the nanosensor network to measure local and circulating cytokine levels in at least eight models of chronic disease, including: cardiovascular disease, cancer, neurodegenerative disease, and autoimmune disease. Future work will be extended to infectious disease, chronic renal disease, musculoskeletal disease, and others. In each disease model, we will couple traditional assessments of inflammation and immune response, as evaluated by weekly blood draws coupled with enzymatic immunoassays. Local inflammation will also be evaluated at the time of sacrifice via single-cell transcriptomic sequencing and immunohistochemical staining. Kinetic cytokine measurements will be obtained via the nanosensor network, deployed in at least 7 locations in each animal, 2 local and 2 systemic, via hydrogel injection. Each will be measured daily for kinetic cytokine quantification prior to and immediately after disease initiation, during chronic progression, and during end-stage disease. Sensor measurement will be performed via whole-animal imaging and simple 3-second light excitation non-invasively from outside the animal. These sensors will provide real-time, long-term quantification of cytokine concentrations throughout disease progression. We expect to understand kinetic cytokine changes in the inflection from acute to chronic inflammatory responses and the pro-inflammatory contribution of multiple organs during disease development. We will investigate pro-inflammatory cytokine signatures for each disease at specific times in its development, providing scientists studying each field difficult-to-obtain dynamic data and further insight into the pathogenesis of chronic disease.


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 = $3,456 )
2026	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	5	12/17/2025	NON-COMPETING CONTINUATION	-$361,734
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	002	6	3/3/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	001	6	12/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$365,190
														Subtotal = $3,456

Issue Date FY: 2025 ( Subtotal = $392,500 )
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	5	6/2/2025	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2024 ( Subtotal = $413,562 )
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	4	5/20/2024	NON-COMPETING CONTINUATION	$392,500
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	4	5/21/2024	SUPPLEMENT FOR EXPANSION	$21,062
														Subtotal = $413,562

Issue Date FY: 2023 ( Subtotal = $726,326 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	002	3	7/31/2023	SUPPLEMENT FOR EXPANSION	$249,578
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	3	5/25/2023	SUPPLEMENT FOR EXPANSION	$84,248
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	3	5/24/2023	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $726,326

Issue Date FY: 2022 ( Subtotal = $455,686 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	2	5/6/2022	NON-COMPETING CONTINUATION	$392,500
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	2	8/31/2022	SUPPLEMENT FOR EXPANSION	$63,186
														Subtotal = $455,686

Issue Date FY: 2021 ( Subtotal = $392,500 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	1	7/29/2021	NEW	$392,500
														Subtotal = $392,500

Grand Total All Awards = $2,384,030

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Integrating Real-Time Multi-System Cytokine Signaling in Chronic Disease

Award Number: R35GM142833

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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