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A temporospatial analysis of epithelial integrity following vocal fold injury

Award Number: R03DC011355
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2011
PERIOD OF PERFORMANCE END DATE: 06/30/2016

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A temporospatial analysis of epithelial integrity following vocal fold injury - DESCRIPTION (provided by applicant): Mucosal remodeling due to vocal fold irritation, infection or injury causes poor voice quality which can result in significant psychosocial and financial costs to the individual. The biological mechanisms underlying vocal fold mucosa remodeling are not known. However, compromised epithelial integrity is implicated in acute and chronic mucosal remodeling in other airway tissue; when epithelium is damaged, its role as a physical and biochemical barrier protecting underlying tissue from insults from the external environment is lost. Rapid and complete restoration of a fully developed epithelium following injury is therefore critical to promote mucosal defense and healing. Our long-term goal is to identify the role of vocal fold epithelial cells in modulating mucosal remodeling in response to injury in order to improve prevention and management of voice disorders. The overall objective of this proposal is to develop a detailed timeline of molecular, cellular and functional changes in epithelium during the acute and chronic phases of wound repair. Concurrent examination of cellular and extracellular changes in lamina propria will permit a holistic analysis of vocal fold mucosal wound healing. We will implement a prospective, double-blind, randomized, controlled experimental study in an animal model to examine cellular and molecular changes in vocal fold epithelium following acute injury. Immuno-histochemistry using transmission electron microscopy and light microscopy and permeability assays will be performed to assess restoration of intercellular and cell-substrate junctions, determine epithelial barrier integrity, and examine the distribution of epidermal growth factor receptors (EGFR) and two growth factors that regulate EGFR activation (EGF and TGF2) in epithelium at critical time points following injury. Chronic aberrant or incomplete epithelial regeneration of cell junctions, persistent 'leakiness' or atypical distribution of EGFR will indicate that vocal folds are at risk for ongoing inflammation, perpetuation of mucosal remodeling, and development or recurrence of vocal fold pathologies post injury. Results of the proposed study will have a significant impact on the field of laryngology, because knowledge of cellular and molecular changes in epithelium during wound healing, when integrated with our understanding of remodeling in the lamina propria following injury, will allow development of a holistic model of mucosal repair; provide a basis for examining epithelial-mesenchyme interactions in wound healing; and add to the knowledge base needed to develop novel cytoprotective interventions to hasten and optimize mucosal repair following surgery as well as following other mechanical, chemical, and biological insults.


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: 2017 ( Subtotal = $0 )
2017	2013	SACRED HEART UNIVERSITY INCORPORATED	5151 PARK AVE	FAIRFIELD	CT	06825	GREATER BRIDGEPORT	USA	Research Related to Deafness and Communication Disorders	000	4	1/9/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = -$18,935 )
2015	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	3	12/22/2014	NON-COMPETING CONTINUATION	-$142,975
2015	2013	SACRED HEART UNIVERSITY	5151 PARK AVENUE	FAIRFIELD	CT	06825	GREATER BRIDGEPORT	USA	Research Related to Deafness and Communication Disorders	001	4	12/22/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$124,040
2015	2013	SACRED HEART UNIVERSITY INCORPORATED	5151 PARK AVENUE	FAIRFIELD	CT	06432		USA	Research Related to Deafness and Communication Disorders	002	4	4/20/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = -$18,935

Issue Date FY: 2013 ( Subtotal = $142,975 )
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	3	6/17/2013	NON-COMPETING CONTINUATION	$142,975
														Subtotal = $142,975

Issue Date FY: 2012 ( Subtotal = $150,500 )
2012	2012	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	2	6/26/2012	NON-COMPETING CONTINUATION	$150,500
														Subtotal = $150,500

Issue Date FY: 2011 ( Subtotal = $150,500 )
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	1	6/30/2011	NEW	$150,500
														Subtotal = $150,500

Grand Total All Awards = $425,040

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A temporospatial analysis of epithelial integrity following vocal fold injury

Award Number: R03DC011355

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2011

PERIOD OF PERFORMANCE END DATE: 06/30/2016

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