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Neutrophil migration and inflammation

Award Number: R35GM119787
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: 08/11/2016
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Neutrophil migration and inflammation - Inflammation presents as swelling, redness, heat, and lost-of-function and is essential for the restoration of tissue homeostasis after injury and infection. Neutrophils are the major effector cells of acute inflammation that combat infection, promote wound healing and resolution of inflammation, while contributing to collateral tissue injury. In addition, neutrophils are exploited as vehicles that cross tissue barriers to deliver cargos to inflammation sites. A better understanding of the neutrophil-intrinsic mechanisms that regulate neutrophil migration will have broad translational importance in the prevention and treatment of a wide range of inflammation-related diseases. The challenges associated with studying neutrophils are a limited set of genetic tools and the plasticity of the cells in vivo. To address these challenges, the PI uses zebrafish, a genetically tractable vertebrate model with a well-conserved innate immune system. Findings on neutrophil intrinsic genes that regulate neutrophil migration generated in the zebrafish model are then validated in primary human or murine neutrophils. MicroRNAs are small RNA molecules of 22-24 nt that regulate homeostasis in health and disease. MicroRNA “mimics” and “inhibitors” are emerging as next-generation therapeutics because of their ability to modulate a network of genes. In addition, microRNAs are being used as tools to discover novel regulators of biological processes. A critical gap remains understanding how microRNAs regulate neutrophil function: despite the prominent microRNA profiling studies in neutrophils and in various diseases, microRNA functional studies are scarce. The PI’s lab has been at the forefront of addressing this unmet need by characterizing microRNAs and their targets in neutrophil migration. Building on their recent progress, the first project is to continue charactering microRNAs in regulating neutrophil migration with two sub aims: (1.1) identify microRNA targets as novel regulators of neutrophil migration and inflammation, and (1.2) characterize how RORα regulates neutrophil migration. A separate project is to characterize mechanisms delineating the role of mitochondria in neutrophil migration. Mitochondria fission promotes migration in many cell types, including lymphocytes, presumably by increasing mitochondria localization and ATP production at sites of high energy demand. On contrary, neutrophils possess a highly fused mitochondrial network and primarily use glycolysis for ATP generation, suggesting additional roles of mitochondria outside the realm of ATP. Specifically, the PI seeks to (2.1) characterize how MFN2 regulates neutrophil migration. The hypothesis is that MFN2-mediated mitochondrial-ER contact regulates Rac activation and neutrophil adhesion and migration. The PI will continue to (2.2) identify additional mitochondrial related genes as novel regulators of neutrophil migration and inflammation. An increased understanding of neutrophil migration and inflammation will open multiple fronts in cell biology and immunology. Additionally, as a result of this work, previously underexplored therapeutic possibilities to treat inflammatory diseases will come to light.


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 = $419,512 )
2025	2025	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	001	10	7/11/2025	NON-COMPETING CONTINUATION	$419,512
2025	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	9	11/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $419,512

Issue Date FY: 2024 ( Subtotal = $419,512 )
2024	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	9	7/2/2024	NON-COMPETING CONTINUATION	$419,512
														Subtotal = $419,512

Issue Date FY: 2023 ( Subtotal = $424,068 )
2023	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	001	8	7/31/2023	SUPPLEMENT FOR EXPANSION	$4,556
2023	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	8	7/28/2023	NON-COMPETING CONTINUATION	$419,512
														Subtotal = $424,068

Issue Date FY: 2022 ( Subtotal = $474,175 )
2022	2022	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	003	7	7/21/2022	SUPPLEMENT FOR EXPANSION	$54,663
2022	2022	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	002	7	7/19/2022	NON-COMPETING CONTINUATION	$419,512
2022	2021	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	001	6	6/13/2022	COMPETING CONTINUATION	$52,703
2022	2020	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	5	6/13/2022	SUPPLEMENT FOR EXPANSION	-$52,703
														Subtotal = $474,175

Issue Date FY: 2021 ( Subtotal = $469,619 )
2021	2021	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	001	6	6/11/2021	COMPETING CONTINUATION	$419,512
2021	2021	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	002	6	8/23/2021	SUPPLEMENT FOR EXPANSION	$50,107
2021	2020	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	5	6/2/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $469,619

Issue Date FY: 2020 ( Subtotal = $609,178 )
2020	2020	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	5	7/24/2020	NON-COMPETING CONTINUATION	$369,178
2020	2020	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	001	5	8/5/2020	SUPPLEMENT FOR EXPANSION	$240,000
														Subtotal = $609,178

Issue Date FY: 2019 ( Subtotal = $369,178 )
2019	2019	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	4	7/23/2019	NON-COMPETING CONTINUATION	$369,178
														Subtotal = $369,178

Issue Date FY: 2018 ( Subtotal = $502,118 )
2018	2018	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	001	3	9/19/2018	SUPPLEMENT FOR EXPANSION	$132,940
2018	2018	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	3	7/27/2018	NON-COMPETING CONTINUATION	$369,178
														Subtotal = $502,118

Issue Date FY: 2017 ( Subtotal = $369,178 )
2017	2017	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	2	7/25/2017	NON-COMPETING CONTINUATION	$369,178
														Subtotal = $369,178

Issue Date FY: 2016 ( Subtotal = $369,178 )
2016	2016	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	8/11/2016	NEW	$369,178
														Subtotal = $369,178

Grand Total All Awards = $4,425,716

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Neutrophil migration and inflammation

Award Number: R35GM119787

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: 08/11/2016

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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