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Mentoring Patient Oriented Research in sensory disorders

Award Number: K24DC020986
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Mentoring Patient Oriented Research in sensory disorders - Abstract: Sensory hair cells are required for balance function. Vestibular hair cell degeneration causes balance dysfunction manifested as dizziness and vertigo. In mice, a limited degree of spontaneous regeneration occurs in the utricle, a vestibular organ detecting linear acceleration. Moreover, addition of the transcription factor Atoh1 robust enhances regeneration of hair cells in the mouse utricle, but regenerated hair cells mature only partially relative to native hair cells. In preliminary experiments, we have characterized a novel AAV-ATOH1 construct leading to regeneration of more mature hair cells in the mouse utricle. With the long-term goal of regenerating human hair cells to restore balance function, two major obstacles remain: 1) we have an incomplete understanding of the molecular signatures of human hair cells, supporting cells and hair cell precursors, 2) adult human inner ear tissues are not readily available to test promising therapeutics discovered in animal models. To overcome these obstacles, we have designed a surgical method to procure live utricles from deceased organ donors who typically have normal auditory and vestibular function. We have begun assembling their medical records, single-cell transcriptomes, and histologic sections of utricles. In parallel, we have procured utricles from vestibular schwannoma patients undergoing surgical resection. Here, we propose to increase the recruitment of organ donors and vestibular schwannoma patients and delineate and validate the transcriptomes of hair cells, supporting cells, and hair cell precursors in adult human utricles in these two cohorts (Aim 1). Furthermore, we will determine whether our novel AAV-ATOH1 enhances hair regeneration and maturation in cultured human utricles (Aim 2). Another goal of this award is to further my career as an investigator and mentor in patient- oriented research. To build on my previous experience in bench research and mentoring, this award is designed to protect my time and help me gain knowledge and skills to 1) study human hair cell regeneration and 2) mentor others pursuing patient-oriented research. In summary, we will apply state-of-the art technologies (single-cell RNA-sequencing, gene therapy, bioinformatic strategies) to study vestibular hair cell regeneration in live human utricles. We have assembled a team of collaborators and experienced mentors in patient-oriented research. At the end of this 5-year proposal, we will have 1) delineated transcriptomes of human hair cells, supporting cells, and hair cell precursors, 2) revealed whether novel AAV-ATOH1 enhances regeneration and maturation of human vestibular hair cells, and 3) enhanced my ability to perform and mentor others in patient-oriented research in sensory disorders.


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 = $194,837 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	4	4/6/2026	NON-COMPETING CONTINUATION	$194,837
														Subtotal = $194,837

Issue Date FY: 2025 ( Subtotal = $195,466 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	3	4/23/2025	NON-COMPETING CONTINUATION	$195,466
														Subtotal = $195,466

Issue Date FY: 2024 ( Subtotal = $196,075 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	2	4/16/2024	NON-COMPETING CONTINUATION	$196,075
														Subtotal = $196,075

Issue Date FY: 2023 ( Subtotal = $196,667 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	1	5/1/2023	NEW	$196,667
														Subtotal = $196,667

Grand Total All Awards = $783,045

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Mentoring Patient Oriented Research in sensory disorders

Award Number: K24DC020986

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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