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High dimensional atlas of circulating neutrophils as reporters of solid organ functional status

Award Number: R01ES034235
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/21/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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High dimensional atlas of circulating neutrophils as reporters of solid organ functional status - High dimensional atlas of circulating neutrophils as reporters of solid organ functional status Chronic solid organ diseases (CSODs) collectively account for the majority of deaths in the United States. A central goal in modern medicine is to improve our ability to predict and detect CSODs in order to initiate successful therapeutic interventions early or to install appropriate early preventive measures. Several approaches have been devised to facilitate early detection of disease, including genetic testing and screening modalities such as imaging and laboratory tests. However, considerable number of CSODs lay silent and escape even the most watchful clinical eyes, only appearing when it is too late to reverse the pathophysiology of the disease. The identification of a non-invasive, accessible, sensitive, and comprehensive reporter system that simultaneously appraises the status of many solid organs would widen the window of opportunity for therapeutic intervention before overt disease occurs. Cellular injury and damage, which precede all organ-based disease, trigger an immune response that may be transcriptionally encoded into surveilling immune cells. The blood circulation accesses all solid organs and therefore provides an excellent portal into organ status. Specifically, neutrophils, the most abundant immune cells in humans, infiltrates nearly all organs under homeostasis. Contrary to their reputation as mere non-specific anti-microbial combatants, neutrophils have evolved as heterogeneous, functionally versatile cells that participate in organ homeostasis and mediate CSODs. The advent of high-dimensional approaches such as single-cell cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNA-seq) have revealed numerous previously unknown neutrophil subpopulations with distinct transcriptional features. Moreover, tissue-infiltrating neutrophils assume specific organ-defined signatures. Unique from other immune cells, neutrophils do not establish permanent residence in the tissues they sojourn. This feature coupled with the neutrophils' short half-life yet significant transcriptional malleability renders them excellent candidates to serve as sentinels and reporters of organ status. In short, neutrophils that have infiltrated organs potentially return into the systemic circulation with vital organ-specific codes that may predict homeostatic state compared to perturbed, diseased states. This proposal will capitalize on these features of neutrophils to create a comprehensive atlas of their transcriptomics signatures, such that any tissue-specific dysregulation would be detected as an alteration in these transcriptional signatures. If successful, we envision a clinical world where blood analysis of neutrophil transcriptomic features would unveil lurking disease far before symptoms develop, prompting early intervention.


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: 2025 ( Subtotal = $415,836 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Trans-NIH Research Support	000	6	6/12/2025	NON-COMPETING CONTINUATION	$415,836
														Subtotal = $415,836

Issue Date FY: 2024 ( Subtotal = $400,882 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Trans-NIH Research Support	000	5	6/17/2024	NON-COMPETING CONTINUATION	$400,882
														Subtotal = $400,882

Issue Date FY: 2023 ( Subtotal = $426,302 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Trans-NIH Research Support	000	4	7/25/2023	NON-COMPETING CONTINUATION	$426,302
														Subtotal = $426,302

Issue Date FY: 2022 ( Subtotal = $435,274 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Trans-NIH Research Support	002	3	7/4/2022	NON-COMPETING CONTINUATION	$435,274
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Trans-NIH Research Support	001	2	4/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$388,748
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Trans-NIH Research Support	000	1	4/20/2022	NEW	-$388,748
														Subtotal = $435,274

Issue Date FY: 2021 ( Subtotal = $388,748 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Trans-NIH Research Support	000	1	9/17/2021	NEW	$388,748
														Subtotal = $388,748

Grand Total All Awards = $2,067,042

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High dimensional atlas of circulating neutrophils as reporters of solid organ functional status

Award Number: R01ES034235

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/21/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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