Destruction of hair cells in the human ear results in irreversible loss of equilibrium or hearing sensitivity since our ears do not produce hair cells after birth. Recently, as an NIH Postdoctoral Fellow I demonstrated hair cell production occurring perpetually in the ears of sharks and rays. This results in the addition of new hair cells equal to 5 times the number in the human organ of Corti and is accompanied by a 500-fold increase in physiological sensitivity. In these ears, due to the persistence of hair cell production, hair cell damage may be reversible through regeneration at any age. Here in my first application for an NIH research grant I outline a plan to continue investigating this sensory epithelium growth and to test the regenerative abilities of perpetually growing ears. Ototoxic antibiotics and cryogenic surgery will be used to damage hair cells, then scanning EM will be used to evaluate the ear's ability to generate new hair cells. Regional rates of hair cell production and suspected links between hair cell age and ultrastructure will be measured with microautoradiography. Intracellular staining will be used to describe how terminal branches of statoacoustic neurons expand to contact epithelia that are increasing by thousands of hair cells per year. The regenerative capacity of peripheral statoacoustic neurites and the mechanisms that guide the perpetual growth of these terminals will be studied by denervating growing epithelia. Physiological response changes associated with growth will be investigated further by recording individually from neurons that contact large hair cells, and from others that contact smaller, apparently younger hair cells at the outer edges of growing epithelia. The characteristics of growing hair cell epithelia are common to many forms, including the embryonically developing ears of mammals and the perpetually growing ears of elasmobranchs. The information sought here is essential to understanding the limits and capacities of regeneration and self repair in hair cell epithelia. It pertains directly to possible recovery from sensory-neural hearing loss and balance disorders and to the development of normal and abnormal function in human ears.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Hearing Research Study Section (HAR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Schools of Medicine
United States
Zip Code
Thiede, Benjamin R; Corwin, Jeffrey T (2014) Permeation of fluorophore-conjugated phalloidin into live hair cells of the inner ear is modulated by P2Y receptors. J Assoc Res Otolaryngol 15:13-30
Mann, Zoƫ F; Thiede, Benjamin R; Chang, Weise et al. (2014) A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear. Nat Commun 5:3839
Burns, Joseph C; Corwin, Jeffrey T (2014) Responses to cell loss become restricted as the supporting cells in mammalian vestibular organs grow thick junctional actin bands that develop high stability. J Neurosci 34:1998-2011
Burns, Joseph C; Corwin, Jeffrey T (2013) A historical to present-day account of efforts to answer the question: ""what puts the brakes on mammalian hair cell regeneration?"". Hear Res 297:52-67
Burns, Joseph C; Collado, Maria Sol; Oliver, Eric R et al. (2013) Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes. J Comp Neurol 521:1430-48
Bermingham-McDonogh, Olivia; Corwin, Jeffrey T; Hauswirth, William W et al. (2012) Regenerative medicine for the special senses: restoring the inputs. J Neurosci 32:14053-7
Burns, Joseph C; On, Doan; Baker, Wendy et al. (2012) Over half the hair cells in the mouse utricle first appear after birth, with significant numbers originating from early postnatal mitotic production in peripheral and striolar growth zones. J Assoc Res Otolaryngol 13:609-27
Collado, Maria Sol; Burns, Joseph C; Meyers, Jason R et al. (2011) Variations in shape-sensitive restriction points mirror differences in the regeneration capacities of avian and mammalian ears. PLoS One 6:e23861
Collado, Maria Sol; Thiede, Benjamin R; Baker, Wendy et al. (2011) The postnatal accumulation of junctional E-cadherin is inversely correlated with the capacity for supporting cells to convert directly into sensory hair cells in mammalian balance organs. J Neurosci 31:11855-66
Goodyear, Richard J; Legan, P Kevin; Christiansen, Jeffrey R et al. (2010) Identification of the hair cell soma-1 antigen, HCS-1, as otoferlin. J Assoc Res Otolaryngol 11:573-86

Showing the most recent 10 out of 21 publications