Novel transcription factors for regeneration of functional outer hair cells after noise injury
Abstract
This project extends research completed on a previous grant (N000141210191) where the investigator was able to regenerate hair cells (HCs) from supporting cells (SCs) in vivo in mouse cochleae at neonatal, juvenile and adult ages. The PI achieved these by genetic manipulations of key transcription factors such as Atoh1 specifically in cochlear SCs. However, the SC-to-HC conversion is inefficient and the regenerated HCs were immature and non-functional.Under this proposal, the PI will test whether additional transcription factors are needed to promote efficient HC conversion and maturation. The PI proposes to test 51 novel transcription factors they recently identified by comparing the gene expression profiles of the newly converted HCs and endogenous OHCs and SCs. Most of these 51 novel candidate genes are not conserved in HC regeneration in chicken, fish or mammalian utricle. The PI will first test pools of these transcription factors in neonatal mouse cochlear explant culture and identify those that increase the conversion rate or promote OHC maturation. He proposes to confirm selected transcription factors in vivo for HC regeneration by creating and characterizing transgenic mouse models which will also be subject to noise injury. The strategy resembles the Nobel prize winning strategy used by others for cellular conversion. Proposed studies will identify novel transcription factors that can promote regeneration of functional auditory sensory cells after noise injury. These novel factors will serve as therapeutic targets to restore hearing loss and provide insights for regenerative medicine in hearing research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 08, 2016
- Source ID
- N000141612315
Entities
People
- Jian Zuo
Organizations
- Office of Naval Research
- United States Navy