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Deciphering macrophage versus neutrophil signaling and effector functions in immune responses in vivo

Award Number: R35GM147464
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: 07/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Deciphering macrophage versus neutrophil signaling and effector functions in immune responses in vivo - Project Summary/Abstract Immune responses are the result of a combined effort of multiple cell types. In innate immune responses the activity of both macrophages and neutrophils is important in targeting pathogens, resolving tissue damage, and maintaining homeostasis. My laboratory uses the larval zebrafish model to determine the differential role and functions of these two innate cell types in inflammatory responses. The overarching goal of my research program is to identify specific signaling pathways, including signals, receptors, and effector mechanisms, that are required for the function of macrophages versus neutrophils. During human disease, the function of just a subset of these cells may go awry, yet common treatments target broad pathways that inhibit multiple cell types and therefore cause harmful side effects. Identification of discrete mechanisms used by single cell types in inflammatory disease will provide targets for future precision therapies. We have developed an experimental system in larval zebrafish using the fungal pathogen A. fumigatus that separates the function of macrophages and neutrophils. Over the next five years, we propose to combine this system with genetic targeting tools and chemical inhibitors to interrogate the requirement of intracellular killing mechanisms, cell death pathways, Toll-like receptors, and C-type lectin receptors in macrophage versus neutrophil functions against A. fumigatus and in response to PAMPs and DAMPs. In future research, we will expand our experimental model to interrogate the role of these genes and pathways in other inflammatory scenarios, such as sterile inflammation during auto-inflammatory disease. Altogether, this research will delineate complete pathways differentially required for innate immune cell function.


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 = $381,250 )
2025	2025	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Biomedical Research and Research Training	000	4	5/26/2025	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2024 ( Subtotal = $381,250 )
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Biomedical Research and Research Training	000	3	5/21/2024	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2023 ( Subtotal = $367,337 )
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Biomedical Research and Research Training	001	2	7/5/2023	SUPPLEMENT FOR EXPANSION	$31,837
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Biomedical Research and Research Training	000	2	5/17/2023	NON-COMPETING CONTINUATION	$335,500
														Subtotal = $367,337

Issue Date FY: 2022 ( Subtotal = $335,500 )
2022	2022	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Biomedical Research and Research Training	000	1	7/6/2022	NEW	$335,500
														Subtotal = $335,500

Grand Total All Awards = $1,465,337

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Deciphering macrophage versus neutrophil signaling and effector functions in immune responses in vivo

Award Number: R35GM147464

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: 07/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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