Thursday, November 21, 2024 11/21/2024

Manipulating Macrophage Phenotype to Accelerate Recurrent Laryngeal Nerve Repair

Award Number: R01DC017171
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

PROJECT SUMMARY/ABSTRACT Vocal fold paralysis (VFP) occurs when the recurrent laryngeal nerve (RLN) is injured, most commonly during surgery of the neck. Bilateral injury to the RLN can result in potentially life-threatening airway obstruction and the need for tracheostomy. The RLN can regenerate some of its axons, but in many patients with paralysis some form of intervention is required to correct the airway obstruction and voice changes. This is most frequently achieved through reinnervation of the laryngeal muscles to restore function. Current practice is to wait 6-24 months before any intervention is performed as spontaneous recovery can occur. This delay before repair allows chronic changes in the nerve distal to the site of injury to occur and results in poor recovery. The overall goal of this proposal is to accelerate recovery after RLN injury and reduce the consequences of prolonged denervation before nerve graft. Previous work has focused mainly on events that occur late in the repair and remodeling process. Little is known about how manipulating events in the early stages of repair can be used to improve recovery. We have recently shown that modifying the type of macrophages accumulating at the graft site early after injury increases Schwann cell migration in the regenerative bridge and improves recovery. Our preliminary data show that when graft is delayed the phenotype of macrophages at the repair site is altered. We hypothesize that changes in the function of senescent Schwann cells (SC) in the distal nerve stump are responsible for this change. In this proposal we will evaluate how macrophage and SC function and gene expression are altered after delayed graft. We will determine gene expression, phagocytosis and migration for both cell types and determine the consequences of these changes on tissue remodeling using a variety of techniques including protein expression, the formation of a polarized microvasculature, axon extension and the number of axons reaching their target. Our preliminary data also demonstrate that an exogenous anti-inflammatory ligand can alter macrophage phenotype and promote axon extension and the formation of neuromuscular junctions. We will then test the neuroprotective ability of this ligand to rescue the changes we have identified in delayed repair and then confirm these changes are mediated by macrophages. Finally, we test the ability of manipulation of macrophage phenotype to accelerate recovery after acute injury using a translational animal model. The ability to accelerate recovery following RLN injury, by intervening intra-operatively, would reduce the consequences of delayed repair and improve recovery for patients with VFP.


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 = -$182,324 )
2025	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	5	11/7/2024	NON-COMPETING CONTINUATION	-$182,324
														Subtotal = -$182,324

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	5	10/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $392,500 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	5	6/14/2022	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2021 ( Subtotal = $392,500 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	4	6/18/2021	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2020 ( Subtotal = $392,500 )
2020	2020	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	3	6/23/2020	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2019 ( Subtotal = $392,500 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	2	6/20/2019	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2018 ( Subtotal = $392,500 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Related to Deafness and Communication Disorders	000	1	7/10/2018	NEW	$392,500
														Subtotal = $392,500

Grand Total All Awards = $1,780,176

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Manipulating Macrophage Phenotype to Accelerate Recurrent Laryngeal Nerve Repair

Award Number: R01DC017171

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer