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Decoupling the Mechanobiology of Neutrophil Extracellular Traps (NETs) in Tumor Metastasis

Award Number: SC2GM136523
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: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Decoupling the Mechanobiology of Neutrophil Extracellular Traps (NETs) in Tumor Metastasis - Arvind Chandrasekaran Abstract Mechanical rigidity of a tumor microenvironment (TME) and the surrounding stroma is an important physical parameter that affects cellular functions. Increased Extracellular Matrix (ECM) stiffness is beginning to be considered as a driving factor in tumor initiation, contributing significantly in mediating the transition from dormant to malignant states. However, understanding of the initial mechanisms leading to the pre-pathological amplification in matrix rigidity is still evolving. Neutrophils form the most abundant cell population of the innate immune system, representing 50– 60% of circulating white blood cells and are the first line of defense during inflammation and infection. Under certain conditions, activated neutrophils undergo a form of programmed cell death by releasing decondensed chromatin, histones and DNA into their surrounding ECM, forming three- dimensional protein web structures called Neutrophil Extracellular Traps (NETs). Recent evidences suggest that NETs that are formed around a tumor could be directly associated with tumor metastasis progression. However, the exact mechanisms and the signaling pathways of NETs interactions with the tumor cells and the stroma are still under research. The primary objective of this project proposal is to decipher the mechanobiological implications of NETs, i.e regulation of the mechanical properties of the tissues (such as stiffness and porosity) due to the formation of NETs, specifically in the context of tumor metastasis. The fundamental hypothesis of this proposal is that NETs accumulating around a tumor bind to the proteins present in the ECM, and stiffen the matrix sufficiently enough to induce downstream biological effects related to tumor growth and invasion. The long-term goal of this project is to understand the mechanobiological organization and regulation of NETs in disease processes. A better comprehension of this concept could have paradigm-shifting implications with respect to the development of suitable therapeutic interventions, not just within the context of tumor metastasis but also towards the pathogenesis of other infectious and autoimmune 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 = -$20,971 )
2026	2022	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	000	3	12/2/2025	NON-COMPETING CONTINUATION	-$20,971
														Subtotal = -$20,971

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	000	3	5/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $144,000 )
2022	2022	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST DOWDY BLDG STE 418 221 DOWDY ADM BLDG	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	001	3	6/15/2022	NON-COMPETING CONTINUATION	$14,400
2022	2022	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST DOWDY BLDG STE 418 221 DOWDY ADM BLDG	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	000	3	4/13/2022	NON-COMPETING CONTINUATION	$129,600
														Subtotal = $144,000

Issue Date FY: 2021 ( Subtotal = $144,000 )
2021	2021	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST DOWDY BLDG STE 418 221 DOWDY ADM BLDG	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	000	2	5/12/2021	NON-COMPETING CONTINUATION	$144,000
														Subtotal = $144,000

Issue Date FY: 2020 ( Subtotal = $124,748 )
2020	2020	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST DOWDY BLDG STE 418 221 DOWDY ADM BLDG	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	000	1	6/26/2020	NEW	$124,748
														Subtotal = $124,748

Grand Total All Awards = $391,777

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Decoupling the Mechanobiology of Neutrophil Extracellular Traps (NETs) in Tumor Metastasis

Award Number: SC2GM136523

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: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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